A Comparison of Candidate Seal Designs for Future Docking Systems

NASA Technical Reports Server (NTRS)

Dunlap, Patrick, H., Jr.; Steinetz, Bruce, M.

2012-01-01

NASA is developing a new docking system to support future space exploration missions to low Earth orbit, the Moon, and other destinations. A key component of this system is the seal at the main docking interface which inhibits the loss of cabin air once docking is complete. Depending on the mission, the seal must be able to dock in either a seal-on-flange or seal-on-seal configuration. Seal-on-flange mating would occur when a docking system equipped with a seal docks to a system with a flat metal flange. This would occur when a vehicle docks to a node on the International Space Station. Seal-on-seal mating would occur when two docking systems equipped with seals dock to each other. Two types of seal designs were identified for this application: Gask-O-seals and multi-piece seals. Both types of seals had a pair of seal bulbs to satisfy the redundancy requirement. A series of performance assessments and comparisons were made between the candidate seal designs indicating that they meet the requirements for leak rate and compression and adhesion loads under a range of operating conditions. Other design factors such as part count, integration into the docking system tunnel, seal-on-seal mating, and cost were also considered leading to the selection of the multi-piece seal design for the new docking system. The results of this study can be used by designers of future docking systems and other habitable volumes to select the seal design best-suited for their particular application.

Microgravity experiments of nano-satellite docking mechanism for final rendezvous approach and docking phase

NASA Astrophysics Data System (ADS)

Ui, Kyoichi; Matunaga, Saburo; Satori, Shin; Ishikawa, Tomohiro

2005-09-01

Laboratory for Space Systems (LSS), Tokyo Institute of Technology (Tokyo Tech) conducted three-dimensional microgravity environment experiments about a docking mechanism for mothership-daughtership (MS-DS) nano-satellite using the facility of Japan Micro Gravity Center (JAMIC) with Hokkaido Institute of Technology (HIT). LSS has studied and developed a docking mechanism for MS-DS nano-satellite system in final rendezvous approach and docking phase since 2000. Consideration of the docking mechanism is to mate a nano-satellite stably while remaining control error of relative velocity and attitude because it is difficult for nano-satellite to have complicated attitude control and mating systems. Objective of the experiments is to verify fundamental grasping function based on our proposed docking methodology. The proposed docking sequence is divided between approach/grasping phase and guiding phase. In the approach/grasping phase, the docking mechanism grasps the nano-satellite even though the nano-satellite has relative position and attitude control errors as well as relative velocity in a docking space. In the guiding function, the docking mechanism guides the nano-satellite to a docking port while adjusting its attitude in order to transfer electrical power and fuel to the nano-satellite. In the paper, we describe the experimental system including the docking mechanism, control system, the daughtership system and the release mechanism, and describe results of microgravity experiments in JAMIC.

Six degree of freedom FORTRAN program, ASTP docking dynamics, users guide

NASA Technical Reports Server (NTRS)

Mount, G. O., Jr.; Mikhalkin, B.

1974-01-01

The digital program ASTP Docking Dynamics as outlined is intended to aid the engineer using the program to determine the docking system loads and attendant vehicular motion resulting from docking two vehicles that have an androgynous, six-hydraulic-attenuator, guide ring, docking interface similar to that designed for the Apollo/Soyuz Test Project (ASTP). This program is set up to analyze two different vehicle combinations: the Apollo CSM docking to Soyuz and the shuttle orbiter docking to another orbiter. The subroutine modifies the vehicle control systems to describe one or the other vehicle combinations; the rest of the vehicle characteristics are changed by input data. To date, the program has been used to predict and correlate ASTP docking loads and performance with docking test program results from dynamic testing. The program modified for use on IBM 360 computers. Parts of the original docking system equations in the areas of hydraulic damping and capture latches are modified to better describe the detail design of the ASTP docking system.

A study of radar cross section measurement techniques

NASA Technical Reports Server (NTRS)

Mcdonald, Malcolm W.

1986-01-01

Past, present, and proposed future technologies for the measurement of radar cross section were studied. The purpose was to determine which method(s) could most advantageously be implemented in the large microwave anechoic chamber facility which is operated at the antenna test range site. The progression toward performing radar cross section measurements of space vehicles with which the Orbital Maneuvering Vehicle will be called upon to rendezvous and dock is a natural outgrowth of previous work conducted in recent years of developing a high accuracy range and velocity sensing radar system. The radar system was designed to support the rendezvous and docking of the Orbital Maneuvering Vehicle with various other space vehicles. The measurement of radar cross sections of space vehicles will be necessary in order to plan properly for Orbital Maneuvering Vehicle rendezvous and docking assignments. The methods which were studied include: standard far-field measurements; reflector-type compact range measurements; lens-type compact range measurement; near field/far field transformations; and computer predictive modeling. The feasibility of each approach is examined.

A web interface for easy flexible protein-protein docking with ATTRACT.

PubMed

de Vries, Sjoerd J; Schindler, Christina E M; Chauvot de Beauchêne, Isaure; Zacharias, Martin

2015-02-03

Protein-protein docking programs can give valuable insights into the structure of protein complexes in the absence of an experimental complex structure. Web interfaces can facilitate the use of docking programs by structural biologists. Here, we present an easy web interface for protein-protein docking with the ATTRACT program. While aimed at nonexpert users, the web interface still covers a considerable range of docking applications. The web interface supports systematic rigid-body protein docking with the ATTRACT coarse-grained force field, as well as various kinds of protein flexibility. The execution of a docking protocol takes up to a few hours on a standard desktop computer. Copyright © 2015 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Molecular Docking Simulation of Neuraminidase Influenza A Subtype H1N1 with Potential Inhibitor of Disulfide Cyclic Peptide (DNY, NNY, LRL)

NASA Astrophysics Data System (ADS)

Putra, R. P.; Imaniastuti, R.; Nasution, M. A. F.; Kerami, Djati; Tambunan, U. S. F.

2018-04-01

Oseltamivir resistance as an inhibitor of neuraminidase influenza A virus subtype H1N1 has been reported lately. Therefore, to solve this problem, several kinds of research has been conducted to design and discover disulfide cyclic peptide ligands through molecular docking method, to find the potential inhibitors for neuraminidase H1N1 which then can disturb the virus replication. This research was studied and evaluated the interaction of ligands toward enzyme using molecular docking simulation, which was performed on three disulfide cyclic peptide inhibitors (DNY, LRL, and NNT), along with oseltamivir and zanamivir as the standard ligands using MOE 2008.10 software. The docking simulation shows that all disulfide cyclic peptide ligands have lower Gibbs free binding energies (ΔGbinding) than the standard ligands, with DNY ligand has the lowest ΔGbinding at -7.8544 kcal/mol. Furthermore, these ligands were also had better molecular interactions with neuraminidase than the standards, owing by the hydrogen bonds that were formed during the docking simulation. In the end, we concluded that DNY, LRL and NNT ligands have the potential to be developed as the inhibitor of neuraminidase H1N1.

Design and fabrication of an autonomous rendezvous and docking sensor using off-the-shelf hardware

NASA Technical Reports Server (NTRS)

Grimm, Gary E.; Bryan, Thomas C.; Howard, Richard T.; Book, Michael L.

1991-01-01

NASA Marshall Space Flight Center (MSFC) has developed and tested an engineering model of an automated rendezvous and docking sensor system composed of a video camera ringed with laser diodes at two wavelengths and a standard remote manipulator system target that has been modified with retro-reflective tape and 830 and 780 mm optical filters. TRW has provided additional engineering analysis, design, and manufacturing support, resulting in a robust, low cost, automated rendezvous and docking sensor design. We have addressed the issue of space qualification using off-the-shelf hardware components. We have also addressed the performance problems of increased signal to noise ratio, increased range, increased frame rate, graceful degradation through component redundancy, and improved range calibration. Next year, we will build a breadboard of this sensor. The phenomenology of the background scene of a target vehicle as viewed against earth and space backgrounds under various lighting conditions will be simulated using the TRW Dynamic Scene Generator Facility (DSGF). Solar illumination angles of the target vehicle and candidate docking target ranging from eclipse to full sun will be explored. The sensor will be transportable for testing at the MSFC Flight Robotics Laboratory (EB24) using the Dynamic Overhead Telerobotic Simulator (DOTS).

Low Impact Docking System (LIDS)

NASA Technical Reports Server (NTRS)

LaBauve, Tobie E.

2009-01-01

Since 1996, NASA has been developing a docking system that will simplify operations and reduce risks associated with mating spacecraft. This effort has focused on developing and testing an original, reconfigurable, active, closed-loop, force-feedback controlled docking system using modern technologies. The primary objective of this effort has been to design a docking interface that is tunable to the unique performance requirements for all types of mating operations (i.e. docking and berthing, autonomous and piloted rendezvous, and in-space assembly of vehicles, modules and structures). The docking system must also support the transfer of crew, cargo, power, fluid, and data. As a result of the past 10 years of docking system advancement, the Low Impact Docking System or LIDS was developed. The current LIDS design incorporates the lessons learned and development experiences from both previous and existing docking systems. LIDS feasibility was established through multiple iterations of prototype hardware development and testing. Benefits of LIDS include safe, low impact mating operations, more effective and flexible mission implementation with an anytime/anywhere mating capability, system level redundancy, and a more affordable and sustainable mission architecture with reduced mission and life cycle costs. In 1996 the LIDS project, then known as the Advanced Docking Berthing System (ADBS) project, launched a four year developmental period. At the end of the four years, the team had built a prototype of the soft-capture hardware and verified the control system that will be used to control the soft-capture system. In 2001, the LIDS team was tasked to work with the X- 38 Crew Return Vehicle (CRV) project and build its first Engineering Development Unit (EDU).

Linear Actuator System for the NASA Docking System

NASA Technical Reports Server (NTRS)

Dick, Brandon N.; Oesch, Christopher; Rupp, Timothy W.

2017-01-01

The Linear Actuator System (LAS) is a major sub-system within the NASA Docking System (NDS). The NDS Block 1 will be used on the Boeing Crew Space Transportation (CST-100) system to achieve docking with the International Space Station. Critical functions in the Soft Capture aspect of docking are performed by the LAS. This paper describes the general function of the LAS, the system's key requirements and technical challenges, and the development and qualification approach for the system.

Performance of a docking/molecular dynamics protocol for virtual screening of nutlin-class inhibitors of Mdmx.

PubMed

Bharatham, Nagakumar; Finch, Kristin E; Min, Jaeki; Mayasundari, Anand; Dyer, Michael A; Guy, R Kiplin; Bashford, Donald

2017-06-01

A virtual screening protocol involving docking and molecular dynamics has been tested against the results of fluorescence polarization assays testing the potency of a series of compounds of the nutlin class for inhibition of the interaction between p53 and Mdmx, an interaction identified as a driver of certain cancers. The protocol uses a standard docking method (AutoDock) with a cutoff based on the AutoDock score (ADscore), followed by molecular dynamics simulation with a cutoff based on root-mean-square-deviation (RMSD) from the docked pose. An analysis of the experimental and computational results shows modest performance of ADscore alone, but dramatically improved performance when RMSD is also used. Published by Elsevier Inc.

Magnetic docking aid for orbiter to ISS docking

NASA Technical Reports Server (NTRS)

Schneider, William C.; Nagy, Kornel; Schliesing, John A.

1996-01-01

The present docking system for the Orbiter uses mechanical capture latches that are actuated by contact forces. The forces are generated when the two approaching masses collide at the docking mechanism. There is always a trade-off between having high enough momentum to effect capture and low enough momentum to avoid structural overload or unacceptable angular displacements. The use of the present docking system includes a contact thrusting maneuver that causes high docking loads to be included into Space Station. A magnetic docking aid has been developed to reduce the load s during docking. The magnetic docking aid is comprised of two extendible booms that are attached adjacent to the docking structure with electromagnets attached on the end of the boom. On the mating vehicle, two steel plates are attached. As the Orbiter approaches Space Station, the booms are extended, and the magnets attach to the actuated (without thrusting), by slowly driving the extendible booms to the stowed position, thus reacting the load into the booms. This results in a docking event that has lower loads induced into Space Station structure. This method also greatly simplifies the Station berthing tasks, since the Shuttle Remote Manipulation System (SRMS) arm need only place the element to be berthed on the magnets (no load required), rather than firing the Reaction Control System (RCS) jets to provide the required force for capture latch actuation. The Magnetic Docking Aid was development testing on a six degree-of-freedom (6 DOF) system at JSC.

Intelligence Level Performance Standards Research for Autonomous Vehicles

PubMed Central

Bostelman, Roger B.; Hong, Tsai H.; Messina, Elena

2017-01-01

United States and European safety standards have evolved to protect workers near Automatic Guided Vehicles (AGV’s). However, performance standards for AGV’s and mobile robots have only recently begun development. Lessons can be learned from research and standards efforts for mobile robots applied to emergency response and military applications. Research challenges, tests and evaluations, and programs to develop higher intelligence levels for vehicles can also used to guide industrial AGV developments towards more adaptable and intelligent systems. These other efforts also provide useful standards development criteria for AGV performance test methods. Current standards areas being considered for AGVs are for docking, navigation, obstacle avoidance, and the ground truth systems that measure performance. This paper provides a look to the future with standards developments in both the performance of vehicles and the dynamic perception systems that measure intelligent vehicle performance. PMID:28649189

Intelligence Level Performance Standards Research for Autonomous Vehicles.

PubMed

Bostelman, Roger B; Hong, Tsai H; Messina, Elena

2015-01-01

United States and European safety standards have evolved to protect workers near Automatic Guided Vehicles (AGV's). However, performance standards for AGV's and mobile robots have only recently begun development. Lessons can be learned from research and standards efforts for mobile robots applied to emergency response and military applications. Research challenges, tests and evaluations, and programs to develop higher intelligence levels for vehicles can also used to guide industrial AGV developments towards more adaptable and intelligent systems. These other efforts also provide useful standards development criteria for AGV performance test methods. Current standards areas being considered for AGVs are for docking, navigation, obstacle avoidance, and the ground truth systems that measure performance. This paper provides a look to the future with standards developments in both the performance of vehicles and the dynamic perception systems that measure intelligent vehicle performance.

Multilevel Parallelization of AutoDock 4.2.

PubMed

Norgan, Andrew P; Coffman, Paul K; Kocher, Jean-Pierre A; Katzmann, David J; Sosa, Carlos P

2011-04-28

Virtual (computational) screening is an increasingly important tool for drug discovery. AutoDock is a popular open-source application for performing molecular docking, the prediction of ligand-receptor interactions. AutoDock is a serial application, though several previous efforts have parallelized various aspects of the program. In this paper, we report on a multi-level parallelization of AutoDock 4.2 (mpAD4). Using MPI and OpenMP, AutoDock 4.2 was parallelized for use on MPI-enabled systems and to multithread the execution of individual docking jobs. In addition, code was implemented to reduce input/output (I/O) traffic by reusing grid maps at each node from docking to docking. Performance of mpAD4 was examined on two multiprocessor computers. Using MPI with OpenMP multithreading, mpAD4 scales with near linearity on the multiprocessor systems tested. In situations where I/O is limiting, reuse of grid maps reduces both system I/O and overall screening time. Multithreading of AutoDock's Lamarkian Genetic Algorithm with OpenMP increases the speed of execution of individual docking jobs, and when combined with MPI parallelization can significantly reduce the execution time of virtual screens. This work is significant in that mpAD4 speeds the execution of certain molecular docking workloads and allows the user to optimize the degree of system-level (MPI) and node-level (OpenMP) parallelization to best fit both workloads and computational resources.

Linear Actuator System for the NASA Docking System

NASA Technical Reports Server (NTRS)

Dick, Brandon; Oesch, Chris

2017-01-01

The Linear Actuator System (LAS) is a major sub-system within the NASA Docking System (NDS). The NDS Block 1 will be used on the Boeing Crew Space Transportation (CST-100) system to achieve docking with the International Space Station. Critical functions in the Soft Capture aspect of docking are performed by the LAS, which implements the Soft Impact Mating and Attenuation Concept (SIMAC). This paper describes the general function of the LAS, the system's key requirements and technical challenges, and the development and qualification approach for the system.

Androgynous, Reconfigurable Closed Loop Feedback Controlled Low Impact Docking System With Load Sensing Electromagnetic Capture Ring

NASA Technical Reports Server (NTRS)

Lewis, James L. (Inventor); Carroll, Monty B. (Inventor); Morales, Ray H. (Inventor); Le, Thang D. (Inventor)

2002-01-01

The present invention relates to a fully androgynous, reconfigurable closed loop feedback controlled low impact docking system with load sensing electromagnetic capture ring. The docking system of the present invention preferably comprises two Docking- assemblies, each docking assembly comprising a load sensing ring having an outer face, one of more electromagnets, one or more load cells coupled to said load sensing ring. The docking assembly further comprises a plurality of actuator arms coupled to said load sensing ring and capable of dynamically adjusting the orientation of said load sensing ring and a reconfigurable closed loop control system capable of analyzing signals originating from said plurality of load cells and of outputting real time control for each of the actuators. The docking assembly of the present invention incorporates an active load sensing system to automatically dynamically adjust the load sensing ring during capture instead of requiring significant force to push and realign the ring.

Spacecraft capture and docking system

NASA Technical Reports Server (NTRS)

Kong, Kinyuen (Inventor); Rafeek, Shaheed (Inventor); Myrick, Thomas (Inventor)

2001-01-01

A system for capturing and docking an active craft to a passive craft has a first docking assembly on the active craft with a first contact member and a spike projecting outwardly, a second docking assembly on the passive craft having a second contact member and a flexible net deployed over a target area with an open mesh for capturing the end of the spike of the active craft, and a motorized net drive for reeling in the net and active craft to mate with the passive craft's docking assembly. The spike has extendable tabs to allow it to become engaged with the net. The net's center is coupled to a net spool for reeling in. An alignment funnel has inclined walls to guide the net and captured spike towards the net spool. The passive craft's docking assembly includes circumferentially spaced preload wedges which are driven to lock the wedges against the contact member of the active craft. The active craft's docking assembly includes a rotary table and drive for rotating it to a predetermined angular alignment position, and mating connectors are then engaged with each other. The system may be used for docking spacecraft in zero or low-gravity environments, as well as for docking underwater vehicles, docking of ancillary craft to a mother craft in subsonic flight, in-flight refueling systems, etc.

AGOR 28

DTIC Science & Technology

2015-11-20

unclassified c. THIS PAGE unclassified Standard Form 298 (Rev. 8-98) Prescribed by ANSI Std Z39-18 2 Exhaust Baffles • December Dry ...Docking Canceled – The floating dry dock is not certified so the docking has been canceled. Divers should do hull and prop cleaning prior to builders...operating temperature of 125-degrees F. A cooler may be necessary to correct this issue. • Uncontaminated Sea Chest – Reports from Armstrong indicate

Advanced Docking System With Magnetic Initial Capture

NASA Technical Reports Server (NTRS)

Lewis, James L.; Carroll, Monty B.; Morales, Ray; Le, Thang

2004-01-01

An advanced docking system is undergoing development to enable softer, safer docking than was possible when using prior docking systems. This system is intended for original use in docking of visiting spacecraft and berthing the Crew Return Vehicle at the International Space Station (ISS). The system could also be adapted to a variety of other uses in outer space and on Earth, including mating submersible vehicles, assembling structures, and robotic berthing/handling of payloads and cargo. Heretofore, two large spacecraft have been docked by causing the spacecraft to approach each other at a speed sufficient to activate capture latches - a procedure that results in large docking loads and is made more difficult because of the speed. The basic design and mode of operation of the present advanced docking system would eliminate the need to rely on speed of approach to activate capture latches, thereby making it possible to reduce approach speed and thus docking loads substantially. The system would comprise an active subsystem on one spacecraft and a passive subsystem on another spacecraft with which the active subsystem will be docked. The passive subsystem would include an extensible ring containing magnetic striker plates and guide petals. The active subsystem would include mating guide petals and electromagnets containing limit switches and would be arranged to mate with the magnetic striker plates and guide petals of the passive assembly. The electromagnets would be carried on (but not rigidly attached to) a structural ring that would be instrumented with load sensors. The outputs of the sensors would be sent, along with position information, as feedback to an electronic control subsystem. The system would also include electromechanical actuators that would extend or retract the ring upon command by the control subsystem.

Analyses of the dynamic docking test system for advanced mission docking system test programs. [Apollo Soyuz Test Project

NASA Technical Reports Server (NTRS)

Gates, R. M.; Williams, J. E.

1974-01-01

Results are given of analytical studies performed in support of the design, implementation, checkout and use of NASA's dynamic docking test system (DDTS). Included are analyses of simulator components, a list of detailed operational test procedures, a summary of simulator performance, and an analysis and comparison of docking dynamics and loads obtained by test and analysis.

Spacecraft Docking System

NASA Technical Reports Server (NTRS)

Ghofranian, Siamak (Inventor); Chuang, Li-Ping Christopher (Inventor); Motaghedi, Pejmun (Inventor)

2016-01-01

A method and apparatus for docking a spacecraft. The apparatus comprises elongate members, movement systems, and force management systems. The elongate members are associated with a docking structure for a spacecraft. The movement systems are configured to move the elongate members axially such that the docking structure for the spacecraft moves. Each of the elongate members is configured to move independently. The force management systems connect the movement systems to the elongate members and are configured to limit a force applied by the each of the elongate members to a desired threshold during movement of the elongate members.

Does transition from the da Vinci Si to Xi robotic platform impact single-docking technique for robot-assisted laparoscopic nephroureterectomy?

PubMed

Patel, Manish N; Aboumohamed, Ahmed; Hemal, Ashok

2015-12-01

To describe our robot-assisted nephroureterectomy (RNU) technique for benign indications and RNU with en bloc excision of bladder cuff (BCE) and lymphadenectomy (LND) for malignant indications using the da Vinci Si and da Vinci Xi robotic platform, with its pros and cons. The port placement described for Si can be used for standard and S robotic systems. This is the first report in the literature on the use of the da Vinci Xi robotic platform for RNU. After a substantial experience of RNU using different da Vinci robots from the standard to the Si platform in a single-docking fashion for benign and malignant conditions, we started using the newly released da Vinci Xi robot since 2014. The most important differences are in port placement and effective use of the features of da Vinci Xi robot while performing simultaneous upper and lower tract surgery. Patient positioning, port placement, step-by-step technique of single docking RNU-LND-BCE using the da Vinci Si and da Vinci Xi robot are shown in an accompanying video with the goal that centres using either robotic system benefit from the hints and tips. The first segment of video describes RNU-LND-BCE using the da Vinci Si followed by the da Vinci Xi to highlight differences. There was no need for patient repositioning or robot re-docking with the new da Vinci Xi robotic platform. We have experience of using different robotic systems for single docking RNU in 70 cases for benign (15) and malignant (55) conditions. The da Vinci Xi robotic platform helps operating room personnel in its easy movement, allows easier patient side-docking with the help of its boom feature, in addition to easy and swift movements of the robotic arms. The patient clearance feature can be used to avoid collision with the robotic arms or the patient's body. In patients with challenging body habitus and in situations where bladder cuff management is difficult, modifications can be made through reassigning the camera to a different port with utilisation of the retargeting feature of the da Vinci Xi when working on the bladder cuff or in the pelvis. The vision of the camera used for da Vinci Xi was initially felt to be inferior to that of the da Vinci Si; however, with a subsequent software upgrade this was much improved. The base of the da Vinci Xi is bigger, which does not slide and occasionally requires a change in table placement/operating room setup, and requires side-docking especially when dealing with very tall and obese patients for pelvic surgery. RNU alone or with LND-BCE is a challenging surgical procedure that addresses the upper and lower urinary tract simultaneously. Single docking and single robotic port placement for RNU-LND-BCE has evolved with the development of different generations of the robotic system. These procedures can be performed safely and effectively using the da Vinci S, Si or Xi robotic platform. The new da Vinci Xi robotic platform is more user-friendly, has easy installation, and is intuitive for surgeons using its features. © 2015 The Authors BJU International © 2015 BJU International Published by John Wiley & Sons Ltd.

Mobile Robot and Mobile Manipulator Research Towards ASTM Standards Development.

PubMed

Bostelman, Roger; Hong, Tsai; Legowik, Steven

2016-01-01

Performance standards for industrial mobile robots and mobile manipulators (robot arms onboard mobile robots) have only recently begun development. Low cost and standardized measurement techniques are needed to characterize system performance, compare different systems, and to determine if recalibration is required. This paper discusses work at the National Institute of Standards and Technology (NIST) and within the ASTM Committee F45 on Driverless Automatic Guided Industrial Vehicles. This includes standards for both terminology, F45.91, and for navigation performance test methods, F45.02. The paper defines terms that are being considered. Additionally, the paper describes navigation test methods that are near ballot and docking test methods being designed for consideration within F45.02. This includes the use of low cost artifacts that can provide alternatives to using relatively expensive measurement systems.

Mobile Robot and Mobile Manipulator Research Towards ASTM Standards Development

PubMed Central

Bostelman, Roger; Hong, Tsai; Legowik, Steven

2017-01-01

Performance standards for industrial mobile robots and mobile manipulators (robot arms onboard mobile robots) have only recently begun development. Low cost and standardized measurement techniques are needed to characterize system performance, compare different systems, and to determine if recalibration is required. This paper discusses work at the National Institute of Standards and Technology (NIST) and within the ASTM Committee F45 on Driverless Automatic Guided Industrial Vehicles. This includes standards for both terminology, F45.91, and for navigation performance test methods, F45.02. The paper defines terms that are being considered. Additionally, the paper describes navigation test methods that are near ballot and docking test methods being designed for consideration within F45.02. This includes the use of low cost artifacts that can provide alternatives to using relatively expensive measurement systems. PMID:28690359

Magnet-Based System for Docking of Miniature Spacecraft

NASA Technical Reports Server (NTRS)

Howard, Nathan; Nguyen, Hai D.

2007-01-01

A prototype system for docking a miniature spacecraft with a larger spacecraft has been developed by engineers at the Johnson Space Center. Engineers working on Mini AERCam, a free-flying robotic camera, needed to find a way to successfully dock and undock their miniature spacecraft to refuel the propulsion and recharge the batteries. The subsystems developed (see figure) include (1) a docking port, designed for the larger spacecraft, which contains an electromagnet, a ball lock mechanism, and a service probe; and (2) a docking cluster, designed for the smaller spacecraft, which contains either a permanent magnet or an electromagnet. A typical docking operation begins with the docking spacecraft maneuvering into position near the docking port on the parent vehicle. The electromagnet( s) are then turned on, and, if necessary, the docking spacecraft is then maneuvered within the capture envelope of the docking port. The capture envelope for this system is approximated by a 5-in. (12.7-cm) cube centered on the front of the docking-port electromagnet and within an angular misalignment of <30 . Thereafter, the magnetic forces draw the smaller spacecraft toward the larger one and this brings the spacecraft into approximate alignment prior to contact. Mechanical alignment guides provide the final rotational alignment into one of 12 positions. Once the docking vehicle has been captured magnetically in the docking port, the ball-lock mechanism is activated, which locks the two spacecraft together. At this point the electromagnet( s) are turned off, and the service probe extended if recharge and refueling are to be performed. Additionally, during undocking, the polarity of one electromagnet can be reversed to provide a gentle push to separate the two spacecraft. This system is currently being incorporated into the design of Mini AERCam vehicle.

Pharmacophore-Based Similarity Scoring for DOCK

PubMed Central

2015-01-01

Pharmacophore modeling incorporates geometric and chemical features of known inhibitors and/or targeted binding sites to rationally identify and design new drug leads. In this study, we have encoded a three-dimensional pharmacophore matching similarity (FMS) scoring function into the structure-based design program DOCK. Validation and characterization of the method are presented through pose reproduction, crossdocking, and enrichment studies. When used alone, FMS scoring dramatically improves pose reproduction success to 93.5% (∼20% increase) and reduces sampling failures to 3.7% (∼6% drop) compared to the standard energy score (SGE) across 1043 protein–ligand complexes. The combined FMS+SGE function further improves success to 98.3%. Crossdocking experiments using FMS and FMS+SGE scoring, for six diverse protein families, similarly showed improvements in success, provided proper pharmacophore references are employed. For enrichment, incorporating pharmacophores during sampling and scoring, in most cases, also yield improved outcomes when docking and rank-ordering libraries of known actives and decoys to 15 systems. Retrospective analyses of virtual screenings to three clinical drug targets (EGFR, IGF-1R, and HIVgp41) using X-ray structures of known inhibitors as pharmacophore references are also reported, including a customized FMS scoring protocol to bias on selected regions in the reference. Overall, the results and fundamental insights gained from this study should benefit the docking community in general, particularly researchers using the new FMS method to guide computational drug discovery with DOCK. PMID:25229837

Orbital docking system centerline color television camera system test

NASA Technical Reports Server (NTRS)

Mongan, Philip T.

1993-01-01

A series of tests was run to verify that the design of the centerline color television camera (CTVC) system is adequate optically for the STS-71 Space Shuttle Orbiter docking mission with the Mir space station. In each test, a mockup of the Mir consisting of hatch, docking mechanism, and docking target was positioned above the Johnson Space Center's full fuselage trainer, which simulated the Orbiter with a mockup of the external airlock and docking adapter. Test subjects viewed the docking target through the CTVC under 30 different lighting conditions and evaluated target resolution, field of view, light levels, light placement, and methods of target alignment. Test results indicate that the proposed design will provide adequate visibility through the centerline camera for a successful docking, even with a reasonable number of light failures. It is recommended that the flight deck crew have individual switching capability for docking lights to provide maximum shadow management and that centerline lights be retained to deal with light failures and user preferences. Procedures for light management should be developed and target alignment aids should be selected during simulated docking runs.

How to benchmark methods for structure-based virtual screening of large compound libraries.

PubMed

Christofferson, Andrew J; Huang, Niu

2012-01-01

Structure-based virtual screening is a useful computational technique for ligand discovery. To systematically evaluate different docking approaches, it is important to have a consistent benchmarking protocol that is both relevant and unbiased. Here, we describe the designing of a benchmarking data set for docking screen assessment, a standard docking screening process, and the analysis and presentation of the enrichment of annotated ligands among a background decoy database.

ART CONCEPTS - ASTP

NASA Image and Video Library

1975-04-01

S75-27289 (May 1975) --- An artist?s concept depicting the American Apollo spacecraft docked with a Soviet Soyuz spacecraft in Earth orbit. During the joint U.S.-USSR Apollo-Soyuz Test Project mission, scheduled for July 1975, the American and Soviet crews will visit one another?s spacecraft while the Soyuz and Apollo are docked for a maximum period of two days. The mission is designed to test equipment and techniques that will establish international crew rescue capability in space, as well as permit future cooperative scientific missions. Each nation has developed separately docking systems based on a mutually agreeable single set of interface design specifications. The major new U.S. program elements are the docking module and docking system necessary to achieve compatibility of rendezvous and docking systems with the USSR-developed hardware to be used on the Soyuz spacecraft. The DM and docking system together with an Apollo Command/Service Module will be launched by a Saturn 1B launch vehicle. This artwork is by Paul Fjeld.

Overall view of test set-up in bldg 13 at JSC during docking set-up tests

NASA Image and Video Library

1974-08-04

S74-27049 (4 Aug. 1974) --- Overall view of test set-up in Building 23 at the Johnson Space Center during testing of the docking mechanisms for the joint U.S.-USSR Apollo-Soyuz Test Project. The cinematic check was being made when this picture was taken. The test control room is on the right. The Soviet-developed docking system is atop the USA-NASA developed docking system. Both American and Soviet engineers can be seen taking part in the docking testing. The ASTP docking mission in Earth orbit is scheduled for July 1975.

Kotov practices the manual docking techniques with the TORU

NASA Image and Video Library

2013-11-22

ISS038-E-006656 (22 Nov. 2013) --- Russian cosmonaut Oleg Kotov, Expedition 38 commander, practices manual docking techniques with the TORU, or telerobotically operated rendezvous system, in the Zvezda Service Module of the International Space Station in preparation for the docking of the Progress 53 spacecraft. Kotov, using the Simvol-TS screen and hand controllers, could manually dock the Progress to the station in the event of a failure of the Kurs automated docking system. The Progress 53 craft is scheduled to complete its automated docking to the aft port of Zvezda at 5:28 p.m. (EST) on Nov. 29.

TORU OBT

NASA Image and Video Library

2014-07-22

ISS040-E-070857 (22 July 2014) --- Russian cosmonaut Alexander Skvortsov, Expedition 40 flight engineer, practices manual docking techniques with the TORU, or telerobotically operated rendezvous system, in the Zvezda Service Module of the International Space Station in preparation for the docking of the Progress 56 spacecraft. Skvortsov, using the Simvol-TS screen and hand controllers, could manually dock the Progress to the station in the event of a failure of the Kurs automated docking system. The Progress 56 craft is scheduled to complete its automated docking to the Pirs docking compartment at 11:30 p.m. (EDT) on July 23, 2014.

Tyurin practices the manual docking techniques with the TORU

NASA Image and Video Library

2013-11-22

ISS038-E-006663 (22 Nov. 2013) --- Russian cosmonaut Mikhail Tyurin, Expedition 38 flight engineer, practices manual docking techniques with the TORU, or telerobotically operated rendezvous system, in the Zvezda Service Module of the International Space Station in preparation for the docking of the Progress 53 spacecraft. Tyurin, using the Simvol-TS screen and hand controllers, could manually dock the Progress to the station in the event of a failure of the Kurs automated docking system. The Progress 53 craft is scheduled to complete its automated docking to the aft port of Zvezda at 5:28 p.m. (EST) on Nov. 29.

TORU OBT

NASA Image and Video Library

2014-07-22

ISS040-E-070859 (22 July 2014) --- Russian cosmonaut Alexander Skvortsov, Expedition 40 flight engineer, practices manual docking techniques with the TORU, or telerobotically operated rendezvous system, in the Zvezda Service Module of the International Space Station in preparation for the docking of the Progress 56 spacecraft. Skvortsov, using the Simvol-TS screen and hand controllers, could manually dock the Progress to the station in the event of a failure of the Kurs automated docking system. The Progress 56 craft is scheduled to complete its automated docking to the Pirs docking compartment at 11:30 p.m. (EDT) on July 23, 2014.

Vinogradov practices docking procedures of the Progress 21 in the SM during Expedition 13

NASA Image and Video Library

2006-04-26

ISS013-E-10225 (26 April 2006) --- Cosmonaut Pavel V. Vinogradov, Expedition 13 commander representing Russia's Federal Space Agency, practices docking procedures with the TORU teleoperated control system in the Zvezda Service Module of the International Space Station in preparation for the docking of the Progress 21 spacecraft. Vinogradov, using the Simvol-TS screen and hand controllers, could manually dock the Progress to the station in the event of a failure of the Kurs automated docking system.

Vinogradov at TORU control system in Zvezda

NASA Image and Video Library

2006-06-26

ISS013-E-42209 (26 June 2006) --- Cosmonaut Pavel V. Vinogradov, Expedition 13 commander representing Russia's Federal Space Agency, practices docking procedures with the TORU teleoperated control system in the Zvezda Service Module of the International Space Station in preparation for the docking of the Progress 22 spacecraft. Vinogradov, using the Simvol-TS screen and hand controllers, could manually dock the Progress to the station in the event of a failure of the Kurs automated docking system.

Low-Impact Mating System for Docking Spacecraft

NASA Technical Reports Server (NTRS)

Lewis, James L.; Robertson, Brandan; Carroll, Monty B.; Le, Thang; Morales, Ray

2008-01-01

A document describes a low-impact mating system suitable for both docking (mating of two free-flying spacecraft) and berthing (in which a robot arm in one spacecraft positions an object for mating with either spacecraft). The low-impact mating system is fully androgynous: it mates with a copy of itself, i.e., all spacecraft and other objects to be mated are to be equipped with identical copies of the system. This aspect of the design helps to minimize the number of unique parts and to standardize and facilitate mating operations. The system includes a closed-loop feedback control subsystem that actively accommodates misalignments between mating spacecraft, thereby attenuating spacecraft dynamics and mitigating the need for precise advance positioning of the spacecraft. The operational characteristics of the mating system can be easily configured in software, during operation, to enable mating of spacecraft having various masses, center-of-gravity offsets, and closing velocities. The system design provides multi-fault tolerance for critical operations: for example, to ensure unmating at a critical time, a redundant unlatching mechanism and two independent pyrotechnic release subsystems are included.

NASA Docking System (NDS) Interface Definitions Document (IDD)

NASA Technical Reports Server (NTRS)

Tabakman, Alexander; England, Warren

2013-01-01

The contents of this document define the integrated performance and interface design for NASA Docking System (NDS) Block 1 and the International Docking Adapter. The intent of this IDD is to provide the interface design for using, installing, and interfacing to the NDS Block 1 that will enable successful docking to the IDA. This document is under the control of the ISS Development Projects Office (OG).

Krikalev works with the TORU teleoperated control system in the SM during Expedition 11

NASA Image and Video Library

2005-06-19

ISS011-E-09184 (18 June 2005) --- Cosmonaut Sergei K. Krikalev, Expedition 11 commander representing Russia's Federal Space Agency, practices docking procedures with the TORU teleoperated control system in the Zvezda Service Module of the International Space Station (ISS) in preparation for the docking of the Progress 18 spacecraft. Krikalev, using the Simvol-TS screen and hand controllers, could manually dock the Progress to the Station in the event of a failure of the Kurs automated docking system.

Tyurin works with the TORU teleoperated control system in the SM during Expedition 14

NASA Image and Video Library

2007-01-20

ISS014-E-12482 (19 Jan. 2007) --- Cosmonaut Mikhail Tyurin, Expedition 14 flight engineer representing Russia's Federal Space Agency, practices docking procedures with the TORU teleoperated control system in the Zvezda Service Module of the International Space Station in preparation for the docking of the Progress 24 spacecraft. Tyurin, using the Simvol-TS screen and hand controllers, could manually dock the Progress to the station in the event of a failure of the Kurs automated docking system.

STS-74 view of MIR Docking module at Pad 39A

NASA Technical Reports Server (NTRS)

1995-01-01

Workers at Launch Pad 39A are preparing to close the payload bay doors on the Space Shuttle Atlantis for its upcoming launch on Mission STS-74 and the second docking with the Russian Space Station Mir. Uppermost in the payload bay is the Orbiter Docking System (ODS), which also flew on the first docking flight between the Space Shuttle and MIR. Lowermost is the primary payload of STS-74, the Russian-built Docking Module. During the mission, the Docking Module will first be attached to ODS and then to Mir. It will be left attached to Mir to become a permanent extension that will afford adequate clearance between the orbiter and the station during future dockings. At left in the payload bay, looking like a very long pole, is the Canadian-built Remote Manipulator System arm that will be used by the crew to hoist the Docking Module and attach it to the ODS.

Kotov in SM during Progress 37P Docking

NASA Image and Video Library

2010-05-01

ISS023-E-031743 (1 May 2010) --- Russian cosmonaut Oleg Kotov, Expedition 23 commander, is pictured at the manual TORU docking system controls in the Zvezda Service Module of the International Space Station just before conducting a manual control docking of the Progress 37 due to a jet failure on the Progress that forced a shutdown of the Kurs automated rendezvous system. Progress 37 docked to the Pirs Docking Compartment at 2:30 p.m. (EDT) on May 1, 2010, after a three-day flight from the Baikonur Cosmodrome in Kazakhstan.

Virtual Screening of Novel Glucosamine-6-Phosphate Synthase Inhibitors.

PubMed

Lather, Amit; Sharma, Sunil; Khatkar, Anurag

2018-01-01

Infections caused by microorganisms are the major cause of death today. The tremendous and improper use of antimicrobial agents leads to antimicrobial resistance. Various currently available antimicrobial drugs are inadequate to control the infections and lead to various adverse drug reactions. Efforts based on computer-aided drug design (CADD) can excavate a large number of databases to generate new, potent hits and minimize the requirement of time as well as money for the discovery of newer antimicrobials. Pharmaceutical sciences also have made development with advances in drug designing concepts. The current research article focuses on the study of various G-6-P synthase inhibitors from literature cited molecular database. Docking analysis was conducted and ADMET data of various molecules was evaluated by Schrodinger Glide and PreADMET software, respectively. Here, the results presented efficacy of various inhibitors towards enzyme G-6-P synthase. Docking scores, binding energy and ADMET data of various molecules showed good inhibitory potential toward G-6-P synthase as compared to standard antibiotics. This novel antimicrobial drug target G-6-P synthase has not so extensively been explored for its application in antimicrobial therapy, so the work done so far proved highly essential. This article has helped the drug researchers and scientists to intensively explore about this wonderful antimicrobial drug target. The Schrodinger, Inc. (New York, USA) software was utilized to carry out the computational calculations and docking studies. The hardware configuration was Intel® core (TM) i5-4210U CPU @ 2.40GHz, RAM memory 4.0 GB under 64-bit window operating system. The ADMET data was calculated by using the PreADMET tool (PreADMET ver. 2.0). All the computational work was completed in the Laboratory for Enzyme Inhibition Studies, Department of Pharmaceutical Sciences, M.D. University, Rohtak, INDIA. Molecular docking studies were carried out to identify the binding affinities and interaction between the inhibitors and the target proteins (G-6-P synthase) by using Glide software (Schrodinger Inc. U.S.A.-Maestro version 10.2). Grid-based Ligand Docking with Energetic (Glide) is one of the most accurate docking softwares available for ligand-protein, protein-protein binding studies. A library of hundreds of available ligands was docked against targeted proteins G-6-P synthase having PDB ID 1moq. Results of docking are shown in Table 1 and Table 2. Results of G-6-P synthase docking showed that some compounds were found to have comparable docking score and binding energy (kj/mol) as compared to standard antibiotics. Many of the ligands showed hydrogen bond interaction, hydrophobic interactions, electrostatic interactions, ionic interactions and π- π stacking with the various amino acid residues in the binding pockets of G-6-P synthase. The docking study estimated free energy of binding, binding pose andglide score and all these parameters provide a promising tool for the discovery of new potent natural inhibitors of G-6-P synthase. These G-6-P synthase inhibitors could further be used as antimicrobials. Here, a detailed binding analysis and new insights of inhibitors from various classes of molecules were docked in binding cavity of G-6-P synthase. ADME and toxicity prediction of these compounds will further accentuate us to study these compounds in vivo. This information will possibly present further expansion of effective antimicrobials against several microbial infections. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Shoreline Classification of the St. Louis River Estuary using Geographic Information Systems and Standard Landuse/Landcover Data Sets

EPA Science Inventory

The St. Louis River Estuary (SLRE) shoreline is ~300 km in length and borders MN and WI from the MN highway 23 downstream to Lake Superior. The shoreline is a complex and diverse mixture of many features from industrial docks and slips in the lower SLRE to complex wetlands and na...

Multiple grid arrangement improves ligand docking with unknown binding sites: Application to the inverse docking problem.

PubMed

Ban, Tomohiro; Ohue, Masahito; Akiyama, Yutaka

2018-04-01

The identification of comprehensive drug-target interactions is important in drug discovery. Although numerous computational methods have been developed over the years, a gold standard technique has not been established. Computational ligand docking and structure-based drug design allow researchers to predict the binding affinity between a compound and a target protein, and thus, they are often used to virtually screen compound libraries. In addition, docking techniques have also been applied to the virtual screening of target proteins (inverse docking) to predict target proteins of a drug candidate. Nevertheless, a more accurate docking method is currently required. In this study, we proposed a method in which a predicted ligand-binding site is covered by multiple grids, termed multiple grid arrangement. Notably, multiple grid arrangement facilitates the conformational search for a grid-based ligand docking software and can be applied to the state-of-the-art commercial docking software Glide (Schrödinger, LLC). We validated the proposed method by re-docking with the Astex diverse benchmark dataset and blind binding site situations, which improved the correct prediction rate of the top scoring docking pose from 27.1% to 34.1%; however, only a slight improvement in target prediction accuracy was observed with inverse docking scenarios. These findings highlight the limitations and challenges of current scoring functions and the need for more accurate docking methods. The proposed multiple grid arrangement method was implemented in Glide by modifying a cross-docking script for Glide, xglide.py. The script of our method is freely available online at http://www.bi.cs.titech.ac.jp/mga_glide/. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

A dynamic motion simulator for future European docking systems

NASA Technical Reports Server (NTRS)

Brondino, G.; Marchal, PH.; Grimbert, D.; Noirault, P.

1990-01-01

Europe's first confrontation with docking in space will require extensive testing to verify design and performance and to qualify hardware. For this purpose, a Docking Dynamics Test Facility (DDTF) was developed. It allows reproduction on the ground of the same impact loads and relative motion dynamics which would occur in space during docking. It uses a 9 degree of freedom, servo-motion system, controlled by a real time computer, which simulates the docking spacecraft in a zero-g environment. The test technique involves and active loop based on six axis force and torque detection, a mathematical simulation of individual spacecraft dynamics, and a 9 degree of freedom servomotion of which 3 DOFs allow extension of the kinematic range to 5 m. The configuration was checked out by closed loop tests involving spacecraft control models and real sensor hardware. The test facility at present has an extensive configuration that allows evaluation of both proximity control and docking systems. It provides a versatile tool to verify system design, hardware items and performance capabilities in the ongoing HERMES and COLUMBUS programs. The test system is described and its capabilities are summarized.

Ground Demonstration on the Autonomous Docking of Two 3U CubeSats Using a Novel Permanent-Magnet Docking Mechanism

NASA Technical Reports Server (NTRS)

Pei, Jing; Murchison, Luke; BenShabat, Adam; Stewart, Victor; Rosenthal, James; Follman, Jacob; Branchy, Mark; Sellers, Drew; Elandt, Ryan; Elliott, Sawyer;

76 FR 27309 - Union Electric Company, dba AmerenUE; Notice of Application for Amendment of License and...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-11

... brief comments up to 6,000 characters, without prior registration, using the eComment system at http... docks, and add 1,330 feet of breakwater. The completed development would have 18 docks (16 boat docks, 1 swim dock, and 1 fishing dock) with 240 boat slips and 156 personal watercraft lifts; boat fueling...

Connection stiffness and dynamical docking process of flux pinned spacecraft modules

NASA Astrophysics Data System (ADS)

Lu, Yong; Zhang, Mingliang; Gao, Dong

2014-02-01

This paper describes a novel kind of potential flux pinned docking system that consists of guidance navigation and control system, the traditional extrusion type propulsion system, and a flux pinned docking interface. Because of characteristics of passive stability of flux pinning, the docking control strategy of flux pinned docking system only needs a series of sequential control rather than necessary active feedback control, as well as avoidance of hazardous collision accident. The flux pinned force between YBaCuO (YBCO) high temperature superconductor bulk and permanent magnet is able to be given vent based on the identical current loop model and improved image dipole model, which can be validated experimentally. Thus, the connection stiffness between two flux pinned spacecraft modules can be calculated based on Hooke's law. This connection stiffness matrix at the equilibrium position has the positive definite performance, which can validate the passively stable connection of two flux pinned spacecraft modules theoretically. Furthermore, the relative orbital dynamical equation of two flux pinned spacecraft modules can be established based on Clohessy-Wiltshire's equations and improved image dipole model. The dynamical docking process between two flux pinned spacecraft modules can be obtained by way of numerical simulation, which suggests the feasibility of flux pinned docking system.

Connection stiffness and dynamical docking process of flux pinned spacecraft modules

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lu, Yong; Zhang, Mingliang, E-mail: niudun12@126.com; Gao, Dong

2014-02-14

This paper describes a novel kind of potential flux pinned docking system that consists of guidance navigation and control system, the traditional extrusion type propulsion system, and a flux pinned docking interface. Because of characteristics of passive stability of flux pinning, the docking control strategy of flux pinned docking system only needs a series of sequential control rather than necessary active feedback control, as well as avoidance of hazardous collision accident. The flux pinned force between YBaCuO (YBCO) high temperature superconductor bulk and permanent magnet is able to be given vent based on the identical current loop model and improvedmore » image dipole model, which can be validated experimentally. Thus, the connection stiffness between two flux pinned spacecraft modules can be calculated based on Hooke's law. This connection stiffness matrix at the equilibrium position has the positive definite performance, which can validate the passively stable connection of two flux pinned spacecraft modules theoretically. Furthermore, the relative orbital dynamical equation of two flux pinned spacecraft modules can be established based on Clohessy-Wiltshire's equations and improved image dipole model. The dynamical docking process between two flux pinned spacecraft modules can be obtained by way of numerical simulation, which suggests the feasibility of flux pinned docking system.« less

22. Detail of interior corner showing truss system, dock no. ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

22. Detail of interior corner showing truss system, dock no. 492. View to south. - Offutt Air Force Base, Looking Glass Airborne Command Post, Nose Docks, On either side of Hangar Access Apron at Northwest end of Project Looking Glass Historic District, Bellevue, Sarpy County, NE

Rational Drug Discovery of HCV Helicase Inhibitor: Improved Docking Accuracy with Multiple Seeding in AutoDock Vina and In Situ Minimization.

PubMed

Lim, See K; Othman, Rozana; Yusof, Rohana; Heh, Choon H

2017-01-01

Hepatitis C is a significant cause for end-stage liver diseases and liver transplantation which affects approximately 3% of the global populations. Despite the current several direct antiviral agents in the treatment of Hepatitis C, the standard treatment for HCV infection is accompanied by several drawbacks, such as adverse side effects, high pricing of medications and the rapid emerging rate of resistant HCV variants. To discover potential inhibitors for HCV helicase through an optimized in silico approach. In this study, a homology model (HCV Genotype 3 helicase) was used as the target and screened through a benzopyran-based virtual library. Multiple-seedings of AutoDock Vina and in situ minimization were to account for the non-deterministic nature of AutoDock Vina search algorithm and binding site flexibility, respectively. ADME/T and interaction analyses were also done on the top hits via FAFDRUG3 web server and Discovery Studio 4.5. This study involved the development of an improved flow for virtual screening via implemention of multiple-seeding screening approach and in situ minimization. With the new docking protocol, the redocked standards have shown better RMSD value in reference to their native conformations. Ten benzopyran-like compounds with satisfactory physicochemical properties were discovered to be potential inhibitors of HCV helicase. ZINC38649350 was identified as the most potential inhibitor. Ten potential HCV helicase inhibitors were discovered via a new docking optimization protocol with better docking accuracy. These findings could contribute to the discovery of novel HCV antivirals and serve as an alternative approach of in silico rational drug discovery. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Dynamic Docking Test System (DDTS) active table computer program NASA Advanced Docking System (NADS)

NASA Technical Reports Server (NTRS)

Gates, R. M.; Jantz, R. E.

1974-01-01

A computer program was developed to describe the three-dimensional motion of the Dynamic Docking Test System active table. The input consists of inertia and geometry data, actuator structural data, forcing function data, hydraulics data, servo electronics data, and integration control data. The output consists of table responses, actuator bending responses, and actuator responses.

STS-74 view of ODS from Payload Changout Room

NASA Technical Reports Server (NTRS)

1995-01-01

Workers at Launch Pad 39A are preparing to close the payload bay doors on the Space Shuttle Atlantis for its upcoming launch on Mission STS-74 and the second docking with the Russian Space Station Mir. Uppermost in the payload bay is the Orbiter Docking System (ODS), which also flew on the first docking flight between the Space Shuttle and MIR. Lowermost is the primary payload of STS-74, the Russian-built Docking Module. During the mission, the Docking Module will first be attached to ODS and then to Mir. It will be left attached to Mir to become a permanent extension that will afford adequate clearance between the orbiter and the station during future dockings. At left in the payload bay, looking like a very long pole, is the Canadian-built Remote Manipulator System arm that will be used by the crew to hoist the Docking Module and attach it to the ODS.

A Hadoop-based Molecular Docking System

NASA Astrophysics Data System (ADS)

Dong, Yueli; Guo, Quan; Sun, Bin

2017-10-01

Molecular docking always faces the challenge of managing tens of TB datasets. It is necessary to improve the efficiency of the storage and docking. We proposed the molecular docking platform based on Hadoop for virtual screening, it provides the preprocessing of ligand datasets and the analysis function of the docking results. A molecular cloud database that supports mass data management is constructed. Through this platform, the docking time is reduced, the data storage is efficient, and the management of the ligand datasets is convenient.

Artist's Concept of the Apollo-Soyuz Test Project

NASA Technical Reports Server (NTRS)

1974-01-01

This artist's concept depicts the Apollo-Soyuz Test Project (ASTP), the first international docking of the U.S.'s Apollo spacecraft and the U.S.S.R.'s Soyuz spacecraft in space. The objective of the ASTP mission was to provide the basis for a standardized international system for docking of marned spacecraft. The Soyuz spacecraft, with Cosmonauts Alexei Leonov and Valeri Kubasov aboard, was launched from the Baikonur Cosmodrome near Tyuratam in the Kazakh, Soviet Socialist Republic, at 8:20 a.m. (EDT) on July 15, 1975. The Apollo spacecraft, with Astronauts Thomas Stafford, Vance Brand, and Donald Slayton aboard, was launched from Launch Complex 39B, Kennedy Space Center, Florida, at 3:50 p.m. (EDT) on July 15, 1975. The Primary objectives of the ASTP were achieved. They performed spacecraft rendezvous, docking and undocking, conducted intervehicular crew transfer, and demonstrated the interaction of U.S. and U.S.S.R. control centers and spacecraft crews. The mission marked the last use of a Saturn launch vehicle. The Marshall Space Flight Center was responsible for development and sustaining engineering of the Saturn IB launch vehicle during the mission.

The Importance of Ligand Conformational Energies in Carbohydrate Docking: Sorting the Wheat from the Chaff

PubMed Central

Nivedha, Anita K.; Makeneni, Spandana; Foley, B. Lachele; Tessier, Matthew B.; Woods, Robert J.

2014-01-01

Docking algorithms that aim to be applicable to a broad range of ligands suffer reduced accuracy because they are unable to incorporate ligand-specific conformational energies. Here, we develop internal energy functions, Carbohydrate Intrinsic (CHI), to account for the rotational preferences of the glycosidic torsion angles in carbohydrates. The relative energies predicted by the CHI energy functions mirror the conformational distributions of glycosidic linkages determined from a survey of oligosaccharide-protein complexes in the Protein Data Bank. Addition of CHI energies to the standard docking scores in Autodock 3, 4.2, and Vina consistently improves pose ranking of oligosaccharides docked to a set of anti-carbohydrate antibodies. The CHI energy functions are also independent of docking algorithm, and with minor modifications, may be incorporated into both theoretical modeling methods, and experimental NMR or X-ray structure refinement programs. PMID:24375430

Quantum.Ligand.Dock: protein-ligand docking with quantum entanglement refinement on a GPU system.

PubMed

Kantardjiev, Alexander A

2012-07-01

Quantum.Ligand.Dock (protein-ligand docking with graphic processing unit (GPU) quantum entanglement refinement on a GPU system) is an original modern method for in silico prediction of protein-ligand interactions via high-performance docking code. The main flavour of our approach is a combination of fast search with a special account for overlooked physical interactions. On the one hand, we take care of self-consistency and proton equilibria mutual effects of docking partners. On the other hand, Quantum.Ligand.Dock is the the only docking server offering such a subtle supplement to protein docking algorithms as quantum entanglement contributions. The motivation for development and proposition of the method to the community hinges upon two arguments-the fundamental importance of quantum entanglement contribution in molecular interaction and the realistic possibility to implement it by the availability of supercomputing power. The implementation of sophisticated quantum methods is made possible by parallelization at several bottlenecks on a GPU supercomputer. The high-performance implementation will be of use for large-scale virtual screening projects, structural bioinformatics, systems biology and fundamental research in understanding protein-ligand recognition. The design of the interface is focused on feasibility and ease of use. Protein and ligand molecule structures are supposed to be submitted as atomic coordinate files in PDB format. A customization section is offered for addition of user-specified charges, extra ionogenic groups with intrinsic pK(a) values or fixed ions. Final predicted complexes are ranked according to obtained scores and provided in PDB format as well as interactive visualization in a molecular viewer. Quantum.Ligand.Dock server can be accessed at http://87.116.85.141/LigandDock.html.

Overview of LIDS Docking and Berthing System Seals

NASA Technical Reports Server (NTRS)

Daniels, Christopher C.; Dunlap, Patrick H., Jr.; deGroh, Henry C., III; Steinetz, Bruce M.; Oswald, Jay J.; Smith, Ian

2007-01-01

This viewgraph presentation describes the Low Impact Docking System (LIDS) docking and berthing system seals. The contents include: 1) Description of the Application: Low Impact Docking System (LIDS); 2) LIDS Seal Locations: Vehicle Undocked (Hatch Closed); 3) LIDS Seal Locations: Mechanical Pass Thru; 4) LIDS Seal Locations: Electrical and Pyro Connectors; 5) LIDS Seal Locations: Vehicle Docked (Hatches Open); 6) LIDS Seal Locations: Main Interface Seal; 7) Main Interface Seal Challenges and Specifications; 8) Approach; 9) Seal Concepts Under Development/Evaluation; 10) Elastomer Material Evaluations; 11) Evaluation of Relevant Seal Properties; 12) Medium-Scale (12") Gask-O-Seal Compression Tests; 13) Medium-Scale Compression Results; 14) Adhesion Forces of Elliptical Top Gask-o-seals; 15) Medium-Scale Seals; 16) Medium-Scale Leakage Results: Effect of Configuration; 17) Full Scale LIDS Seal Test Rig Development; 18) Materials International Space Station Experiment (MISSE 6A and 6B); and 19) Schedule.

DOCK2 regulates cell proliferation through Rac and ERK activation in B cell lymphoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Lei; Nishihara, Hiroshi, E-mail: nisihara@patho2.med.hokudai.ac.jp; Kimura, Taichi

2010-04-23

DOCK2; a member of the CDM protein family, regulates cell motility and cytokine production through the activation of Rac in mammalian hematopoietic cells and plays a pivotal role in the modulation of the immune system. Here we demonstrated the alternative function of DOCK2 in hematopoietic tumor cells, especially in terms of its association with the tumor progression. Immunostaining for DOCK2 in 20 cases of human B cell lymphoma tissue specimens including diffuse large B cell lymphoma and follicular lymphoma revealed the prominent expression of DOCK2 in all of the lymphoma cells. DOCK2-knockdown (KD) of the B cell lymphoma cell lines,more » Ramos and Raji, using the lentiviral shRNA system presented decreased cell proliferation compared to the control cells. Furthermore, the tumor formation of DOCK2-KD Ramos cell in nude mice was significantly abrogated. Western blotting analysis and pull-down assay using GST-PAK-RBD kimeric protein suggested the presence of DOCK2-Rac-ERK pathway regulating the cell proliferation of these lymphoma cells. This is the first report to clarify the prominent role of DOCK2 in hematopoietic malignancy.« less

Rendezvous and Docking for Space Exploration

NASA Technical Reports Server (NTRS)

Machula, M. F.; Crain, T.; Sandhoo, G. S.

2005-01-01

To achieve the exploration goals, new approaches to exploration are being envisioned that include robotic networks, modular systems, pre-positioned propellants and in-space assembly in Earth orbit, Lunar orbit and other locations around the cosmos. A fundamental requirement for rendezvous and docking to accomplish in-space assembly exists in each of these locations. While existing systems and technologies can accomplish rendezvous and docking in low earth orbit, and rendezvous and docking with crewed systems has been successfully accomplished in low lunar orbit, our capability must extend toward autonomous rendezvous and docking. To meet the needs of the exploration vision in-space assembly requiring both crewed and uncrewed vehicles will be an integral part of the exploration architecture. This paper focuses on the intelligent application of autonomous rendezvous and docking technologies to meet the needs of that architecture. It also describes key technology investments that will increase the exploration program's ability to ensure mission success, regardless of whether the rendezvous are fully automated or have humans in the loop.

Development of an autonomous video rendezvous and docking system, phase 2

NASA Technical Reports Server (NTRS)

Tietz, J. C.; Richardson, T. E.

1983-01-01

The critical elements of an autonomous video rendezvous and docking system were built and used successfully in a physical laboratory simulation. The laboratory system demonstrated that a small, inexpensive electronic package and a flight computer of modest size can analyze television images to derive guidance information for spacecraft. In the ultimate application, the system would use a docking aid consisting of three flashing lights mounted on a passive target spacecraft. Television imagery of the docking aid would be processed aboard an active chase vehicle to derive relative positions and attitudes of the two spacecraft. The demonstration system used scale models of the target spacecraft with working docking aids. A television camera mounted on a 6 degree of freedom (DOF) simulator provided imagery of the target to simulate observations from the chase vehicle. A hardware video processor extracted statistics from the imagery, from which a computer quickly computed position and attitude. Computer software known as a Kalman filter derived velocity information from position measurements.

Design and Preliminary Testing of the International Docking Adapter's Peripheral Docking Target

NASA Technical Reports Server (NTRS)

Foster, Christopher W.; Blaschak, Johnathan; Eldridge, Erin A.; Brazzel, Jack P.; Spehar, Peter T.

2015-01-01

The International Docking Adapter's Peripheral Docking Target (PDT) was designed to allow a docking spacecraft to judge its alignment relative to the docking system. The PDT was designed to be compatible with relative sensors using visible cameras, thermal imagers, or Light Detection and Ranging (LIDAR) technologies. The conceptual design team tested prototype designs and materials to determine the contrast requirements for the features. This paper will discuss the design of the PDT, the methodology and results of the tests, and the conclusions pertaining to PDT design that were drawn from testing.

Electro-optical rendezvous and docking sensors

NASA Technical Reports Server (NTRS)

Tubbs, David J.; Kesler, Lynn O.; Sirko, Robert J.

1991-01-01

Electro-optical sensors provide unique and critical functionality for space missions requiring rendezvous, docking, and berthing. McDonnell Douglas is developing a complete rendezvous and docking system for both manned and unmanned missions. This paper examines our sensor development and the systems and missions which benefit from rendezvous and docking sensors. Simulation results quantifying system performance improvements in key areas are given, with associated sensor performance requirements. A brief review of NASA-funded development activities and the current performance of electro-optical sensors for space applications is given. We will also describe current activities at McDonnell Douglas for a fully functional demonstration to address specific NASA mission needs.

Dry dock gate stability modelling

NASA Astrophysics Data System (ADS)

Oktoberty; Widiyanto; Sasono, E. J.; Pramono, S.; Wandono, A. T.

2018-03-01

The development of marine transportation needs in Indonesia increasingly opens national shipyard business opportunities to provide shipbuilding services to the shipbuilding vessels. That emphasizes the stability of prime. The ship's decking door becomes an integral part of the efficient place and the specification of the use of the asset of its operational ease. This study aims to test the stability of Dry Dock gate with the length of 35.4 meters using Maxsurf and Hydromax in analyzing the calculation were in its assessment using interval per 500 mm length so that it can get detail data toward longitudinal and transverse such as studying Ship planning in general. The test result shows dry dock gate meets IMO standard with ballast construction containing 54% and 68% and using fix ballast can produce GMt 1,924 m, tide height 11,357m. The GMt value indicates dry dick gate can be stable and firmly erect at the base of the mouth dry dock. When empty ballast produces GMt 0.996 which means dry dock date is stable, but can easily be torn down. The condition can be used during dry dock gate treatment.

Multi-Axis Independent Electromechanical Load Control for Docking System Actuation Development and Verification Using dSPACE

NASA Technical Reports Server (NTRS)

Oesch, Christopher; Dick, Brandon; Rupp, Timothy

2015-01-01

The development of highly complex and advanced actuation systems to meet customer demands has accelerated as the use of real-time testing technology expands into multiple markets at Moog. Systems developed for the autonomous docking of human rated spacecraft to the International Space Station (ISS), envelope multi-operational characteristics which place unique constraints on an actuation system. Real-time testing hardware has been used as a platform for incremental testing and development for the linear actuation system which controls initial capture and docking for vehicles visiting the ISS. This presentation will outline the role of dSPACE hardware as a platform for rapid control-algorithm prototyping as well as an Electromechanical Actuator (EMA) system dynamic loading simulator, both conducted at Moog to develop the safety critical Linear Actuator System (LAS) of the NASA Docking System (NDS).

The Drosophila SH2-SH3 adapter protein Dock is expressed in embryonic axons and facilitates synapse formation by the RP3 motoneuron.

PubMed

Desai, C J; Garrity, P A; Keshishian, H; Zipursky, S L; Zinn, K

1999-04-01

The Dock SH2-SH3 domain adapter protein, a homolog of the mammalian Nck oncoprotein, is required for axon guidance and target recognition by photoreceptor axons in Drosophila larvae. Here we show that Dock is widely expressed in neurons and at muscle attachment sites in the embryo, and that this expression pattern has both maternal and zygotic components. In motoneurons, Dock is concentrated in growth cones. Loss of zygotic dock function causes a selective delay in synapse formation by the RP3 motoneuron at the cleft between muscles 7 and 6. These muscles often completely lack innervation in late stage 16 dock mutant embryos. RP3 does form a synapse later in development, however, because muscles 7 and 6 are normally innervated in third-instar mutant larvae. The absence of zygotically expressed Dock also results in subtle defects in a longitudinal axon pathway in the embryonic central nervous system. Concomitant loss of both maternally and zygotically derived Dock dramatically enhances these central nervous system defects, but does not increase the delay in RP3 synaptogenesis. These results indicate that Dock facilitates synapse formation by the RP3 motoneuron and is also required for guidance of some interneuronal axons The involvement of Dock in the conversion of the RP3 growth cone into a presynaptic terminal may reflect a role for Dock-mediated signaling in remodeling of the growth cone's cytoskeleton.

Dissecting Nck/Dock signaling pathways in Drosophila visual system.

PubMed

Rao, Yong

2005-01-01

The establishment of neuronal connections during embryonic development requires the precise guidance and targeting of the neuronal growth cone, an expanded cellular structure at the leading tip of a growing axon. The growth cone contains sophisticated signaling systems that allow the rapid communication between guidance receptors and the actin cytoskeleton in generating directed motility. Previous studies demonstrated a specific role for the Nck/Dock SH2/SH3 adapter protein in photoreceptor (R cell) axon guidance and target recognition in the Drosophila visual system, suggesting strongly that Nck/Dock is one of the long-sought missing links between cell surface receptors and the actin cytoskeleton. In this review, I discuss the recent progress on dissecting the Nck/Dock signaling pathways in R-cell growth cones. These studies have identified additional key components of the Nck/Dock signaling pathways for linking the receptor signaling to the remodeling of the actin cytoskeleton in controlling growth-cone motility.

Dissecting Nck/Dock Signaling Pathways in Drosophila Visual System

PubMed Central

2005-01-01

The establishment of neuronal connections during embryonic development requires the precise guidance and targeting of the neuronal growth cone, an expanded cellular structure at the leading tip of a growing axon. The growth cone contains sophisticated signaling systems that allow the rapid communication between guidance receptors and the actin cytoskeleton in generating directed motility. Previous studies demonstrated a specific role for the Nck/Dock SH2/SH3 adapter protein in photoreceptor (R cell) axon guidance and target recognition in the Drosophila visual system, suggesting strongly that Nck/Dock is one of the long-sought missing links between cell surface receptors and the actin cytoskeleton. In this review, I discuss the recent progress on dissecting the Nck/Dock signaling pathways in R-cell growth cones. These studies have identified additional key components of the Nck/Dock signaling pathways for linking the receptor signaling to the remodeling of the actin cytoskeleton in controlling growth-cone motility. PMID:15951852

STS-112 Flight Day 3 Highlights

NASA Technical Reports Server (NTRS)

2002-01-01

During the third flight day of STS-112 (Commander Jeff Ashby, Pilot Pam Melroy and Mission Specialists Sandy Magnus, Piers Sellers, David Wolf and Fyodor Yurchikhin), the Space Shuttle Atlantis begins its final approach to the International Space Station (ISS) with which it will dock. The Chinese mainland is seen, at night, at a height of 242 statute miles. In one section of video from a camera onboard the ISS, Atlantis can be seen to be almost directly below the station, at a distance of several hundred feet. The orbiter's docking system is shown, as it is slowly guided by Ashby towards the forward docking port on the ISS's Destiny Laboratory Module and its forward docking port. Above the docking port, the S0 truss structure can be seen, to which the S1 truss structure in Atlantis' payload bay will be attached during this mission. Also seen are the Unity airlock and other modules. Following the completion of docking, in which an excellent shot of the docking system in hard dock is visible, the hatches between the two crafts are opened and the members of Atlantis are greeted by the very excited members of Expedition 5, who have been aboard the ISS for several months.

Space Tug Docking Study. Volume 1: Executive Summary

NASA Technical Reports Server (NTRS)

1976-01-01

Results of a detailed systems analysis of the entire rendezvous and docking operation to be performed by the all-up space tug are presented. Specific areas investigated include: generating of operational requirements and a data base of candidate operational techniques and subsystem mechanizations; selection and ranking of integrated system designs capable of meeting the requirements generated; and definition of this simulation/demonstration program required to select and prove the most effective manual, autonomous, and hybrid rendezvous and docking systems.

Plugin-docking system for autonomous charging using particle filter

NASA Astrophysics Data System (ADS)

Koyasu, Hiroshi; Wada, Masayoshi

2017-03-01

Autonomous charging of the robot battery is one of the key functions for the sake of expanding working areas of the robots. To realize it, most of existing systems use custom docking stations or artificial markers. By the other words, they can only charge on a few specific outlets. If the limit can be removed, working areas of the robots significantly expands. In this paper, we describe a plugin-docking system for the autonomous charging, which does not require any custom docking stations or artificial markers. A single camera is used for recognizing the 3D position of an outlet socket. A particle filter-based image tracking algorithm which is robust to the illumination change is applied. The algorithm is implemented on a robot with an omnidirectional moving system. The experimental results show the effectiveness of our system.

DockQ: A Quality Measure for Protein-Protein Docking Models

PubMed Central

Basu, Sankar

2016-01-01

The state-of-the-art to assess the structural quality of docking models is currently based on three related yet independent quality measures: Fnat, LRMS, and iRMS as proposed and standardized by CAPRI. These quality measures quantify different aspects of the quality of a particular docking model and need to be viewed together to reveal the true quality, e.g. a model with relatively poor LRMS (>10Å) might still qualify as 'acceptable' with a descent Fnat (>0.50) and iRMS (<3.0Å). This is also the reason why the so called CAPRI criteria for assessing the quality of docking models is defined by applying various ad-hoc cutoffs on these measures to classify a docking model into the four classes: Incorrect, Acceptable, Medium, or High quality. This classification has been useful in CAPRI, but since models are grouped in only four bins it is also rather limiting, making it difficult to rank models, correlate with scoring functions or use it as target function in machine learning algorithms. Here, we present DockQ, a continuous protein-protein docking model quality measure derived by combining Fnat, LRMS, and iRMS to a single score in the range [0, 1] that can be used to assess the quality of protein docking models. By using DockQ on CAPRI models it is possible to almost completely reproduce the original CAPRI classification into Incorrect, Acceptable, Medium and High quality. An average PPV of 94% at 90% Recall demonstrating that there is no need to apply predefined ad-hoc cutoffs to classify docking models. Since DockQ recapitulates the CAPRI classification almost perfectly, it can be viewed as a higher resolution version of the CAPRI classification, making it possible to estimate model quality in a more quantitative way using Z-scores or sum of top ranked models, which has been so valuable for the CASP community. The possibility to directly correlate a quality measure to a scoring function has been crucial for the development of scoring functions for protein structure prediction, and DockQ should be useful in a similar development in the protein docking field. DockQ is available at http://github.com/bjornwallner/DockQ/ PMID:27560519

Apollo-Soyuz test project docking system

NASA Technical Reports Server (NTRS)

Swan, W. L., Jr.

1976-01-01

The United States and Soviet Union in July 1975 successfully completed a joint space mission utilizing each country's spacecraft and the compatible docking system designed and fabricated by each country. The compatible docking system is described, along with the extensive research, development, and testing leading up to the successful mission. It also describes the formulation and implementation of methods for breaking the language barrier, bridging the extensive distances for communication and travel, and adjusting to each country's different culture during the three-year development program.

Progress 23 supply vehicle approach

NASA Image and Video Library

2006-10-26

ISS014-E-06544 (26 Oct. 2006) --- Backdropped by a blue and white Earth, an unpiloted Progress supply vehicle approaches the International Space Station. Progress docked to the aft port of the Zvezda Service Module at 9:29 a.m. (CDT) on Oct. 26. The spacecraft used the automated Kurs system to dock at the aft port of the Zvezda service module. Expedition 14 flight engineer Mikhail Tyurin stood by at the manual Toru docking system controls, but the automated system functioned as designed and manual intervention was not needed.

Analysis and Selection of a Remote Docking Simulation Visual Display System

NASA Technical Reports Server (NTRS)

Shields, N., Jr.; Fagg, M. F.

1984-01-01

The development of a remote docking simulation visual display system is examined. Video system and operator performance are discussed as well as operator command and control requirements and a design analysis of the reconfigurable work station.

Integrated Docking Simulation and Testing with the Johnson Space Center Six-Degree of Freedom Dynamic Test System

NASA Technical Reports Server (NTRS)

Mitchell, Jennifer D.; Cryan, Scott P.; Baker, Kenneth; Martin, Toby; Goode, Robert; Key, Kevin W.; Manning, Thomas; Chien, Chiun-Hong

2008-01-01

The Exploration Systems Architecture defines missions that require rendezvous, proximity operations, and docking (RPOD) of two spacecraft both in Low Earth Orbit (LEO) and in Low Lunar Orbit (LLO). Uncrewed spacecraft must perform automated and/or autonomous rendezvous, proximity operations and docking operations (commonly known as Automated Rendezvous and Docking, AR&D). The crewed versions may also perform AR&D, possibly with a different level of automation and/or autonomy, and must also provide the crew with relative navigation information for manual piloting. The capabilities of the RPOD sensors are critical to the success of the Constellation Program; this is carried as one of the CEV Project top risks. The Exploration Technology Development Program (ETDP) AR&D Sensor Technology Project seeks to reduce this risk by increasing technology maturation of selected relative navigation sensor technologies through testing and simulation. One of the project activities is a series of "pathfinder" testing and simulation activities to integrate relative navigation sensors with the Johnson Space Center Six-Degree-of-Freedom Test System (SDTS). The SDTS will be the primary testing location for the Orion spacecraft s Low Impact Docking System (LIDS). Project team members have integrated the Orion simulation with the SDTS computer system so that real-time closed loop testing can be performed with relative navigation sensors and the docking system in the loop during docking and undocking scenarios. Two relative navigation sensors are being used as part of a "pathfinder" activity in order to pave the way for future testing with the actual Orion sensors. This paper describes the test configuration and test results.

Automated Rendezvous and Capture System Development and Simulation for NASA

NASA Technical Reports Server (NTRS)

Roe, Fred D.; Howard, Richard T.; Murphy, Leslie

2004-01-01

The United States does not have an Automated Rendezvous and Capture/Docking (AR and C) capability and is reliant on manned control for rendezvous and docking of orbiting spacecraft. This reliance on the labor intensive manned interface for control of rendezvous and docking vehicles has a significant impact on the cost of the operation of the International Space Station (ISS) and precludes the use of any U.S. expendable launch capabilities for Space Station resupply. The Soviets have the capability to autonomously dock in space, but their system produces a hard docking with excessive force and contact velocity. Automated Rendezvous and Capture/Docking has been identified as a key enabling technology for the Space Launch Initiative (SLI) Program, DARPA Orbital Express and other DOD Programs. The development and implementation of an AR&C capability can significantly enhance system flexibility, improve safety, and lower the cost of maintaining, supplying, and operating the International Space Station. The Marshall Space Flight Center (MSFC) has conducted pioneering research in the development of an automated rendezvous and capture (or docking) (AR and C) system for U.S. space vehicles. This AR&C system was tested extensively using hardware-in-the-loop simulations in the Flight Robotics Laboratory, and a rendezvous sensor, the Video Guidance Sensor was developed and successfully flown on the Space Shuttle on flights STS-87 and STS-95, proving the concept of a video- based sensor. Further developments in sensor technology and vehicle and target configuration have lead to continued improvements and changes in AR&C system development and simulation. A new Advanced Video Guidance Sensor (AVGS) with target will be utilized on the Demonstration of Autonomous Rendezvous Technologies (DART) flight experiment in 2004.

Synthesis and characterization of curcumin-sulfonamide hybrids: Biological evaluation and molecular docking studies

NASA Astrophysics Data System (ADS)

Banuppriya, Govindharasu; Sribalan, Rajendran; Padmini, Vediappen

2018-03-01

Curcumin-sulfonamide hybrids (4a-e) were synthesized and their in vitro antioxidant, anti-inflammatory and anticancer activities were studied. The synthesized compounds showed a very good potent activity towards antioxidant and anti-inflammatory studies rather than its parent as well as standard. These compounds have exhibited an excellent toxicity effect to the cancer cell lines such as A549 and AGS. The compounds 4a and 4c have showed good anticancer activity than curcumin. The molecular docking studies were also performed against various Epidermal Growth Factor Receptor (EGFR) enzymes. The DFT calculations were also done in order to support the docking results.

Overview of LIDS Docking Seals Development

NASA Technical Reports Server (NTRS)

Dunlap, Pat; Steinetz, Bruce; Daniels, Chris

2008-01-01

NASA is developing a new docking system to support future space exploration missions to low-Earth orbit, the Moon, and Mars. This mechanism, called the Low Impact Docking System (LIDS), is designed to connect pressurized space vehicles and structures including the Crew Exploration Vehicle, International Space Station, and lunar lander. NASA Glenn Research Center (GRC) is playing a key role in developing the main interface seal for this new docking system. These seals will be approximately 147 cm (58 in.) in diameter. GRC is evaluating the performance of candidate seal designs under simulated operating conditions at both sub-scale and full-scale levels. GRC is ultimately responsible for delivering flight hardware seals to NASA Johnson Space Center around 2013 for integration into LIDS flight units.

Autonomous spacecraft rendezvous and docking

NASA Technical Reports Server (NTRS)

Tietz, J. C.; Almand, B. J.

1985-01-01

A storyboard display is presented which summarizes work done recently in design and simulation of autonomous video rendezvous and docking systems for spacecraft. This display includes: photographs of the simulation hardware, plots of chase vehicle trajectories from simulations, pictures of the docking aid including image processing interpretations, and drawings of the control system strategy. Viewgraph-style sheets on the display bulletin board summarize the simulation objectives, benefits, special considerations, approach, and results.

Autonomous spacecraft rendezvous and docking

NASA Astrophysics Data System (ADS)

Tietz, J. C.; Almand, B. J.

A storyboard display is presented which summarizes work done recently in design and simulation of autonomous video rendezvous and docking systems for spacecraft. This display includes: photographs of the simulation hardware, plots of chase vehicle trajectories from simulations, pictures of the docking aid including image processing interpretations, and drawings of the control system strategy. Viewgraph-style sheets on the display bulletin board summarize the simulation objectives, benefits, special considerations, approach, and results.

Vision Based Navigation for Autonomous Cooperative Docking of CubeSats

NASA Astrophysics Data System (ADS)

Pirat, Camille; Ankersen, Finn; Walker, Roger; Gass, Volker

2018-05-01

A realistic rendezvous and docking navigation solution applicable to CubeSats is investigated. The scalability analysis of the ESA Autonomous Transfer Vehicle Guidance, Navigation & Control (GNC) performances and the Russian docking system, shows that the docking of two CubeSats would require a lateral control performance of the order of 1 cm. Line of sight constraints and multipath effects affecting Global Navigation Satellite System (GNSS) measurements in close proximity prevent the use of this sensor for the final approach. This consideration and the high control accuracy requirement led to the use of vision sensors for the final 10 m of the rendezvous and docking sequence. A single monocular camera on the chaser satellite and various sets of Light-Emitting Diodes (LEDs) on the target vehicle ensure the observability of the system throughout the approach trajectory. The simple and novel formulation of the measurement equations allows differentiating unambiguously rotations from translations between the target and chaser docking port and allows a navigation performance better than 1 mm at docking. Furthermore, the non-linear measurement equations can be solved in order to provide an analytic navigation solution. This solution can be used to monitor the navigation filter solution and ensure its stability, adding an extra layer of robustness for autonomous rendezvous and docking. The navigation filter initialization is addressed in detail. The proposed method is able to differentiate LEDs signals from Sun reflections as demonstrated by experimental data. The navigation filter uses a comprehensive linearised coupled rotation/translation dynamics, describing the chaser to target docking port motion. The handover, between GNSS and vision sensor measurements, is assessed. The performances of the navigation function along the approach trajectory is discussed.

External airlock assembly/Mir docking system being loaded

NASA Image and Video Library

1994-11-15

S95-00057 (15 Nov 1994) --- In Rockwell's Building 290 at Downey, California, the external airlock assembly/Mir docking system is rotated into position for crating up for shipment to the Kennedy Space Center (KSC) in Florida. Jointly developed by Rockwell and RSC Energia, the external airlock assembly and Mir docking system will be mounted in the cargo bay of the Space Shuttle Atlantis to enable the shuttle to link up to Russia's Mir space station. The docking system contains hooks and latches compatible with the system currently housed on the Mir's Krystall module, to which Atlantis will attach for the first time next spring. STS-71 will carry two Russian cosmonauts, who will replace a three-man crew aboard Mir including Norman E. Thagard, a NASA astronaut. The combined 10-person crew will conduct almost five days of joint life sciences investigations both aboard Mir and in the Space Shuttle Atlantis's Spacelab module.

DOVIS: an implementation for high-throughput virtual screening using AutoDock.

PubMed

Zhang, Shuxing; Kumar, Kamal; Jiang, Xiaohui; Wallqvist, Anders; Reifman, Jaques

2008-02-27

Molecular-docking-based virtual screening is an important tool in drug discovery that is used to significantly reduce the number of possible chemical compounds to be investigated. In addition to the selection of a sound docking strategy with appropriate scoring functions, another technical challenge is to in silico screen millions of compounds in a reasonable time. To meet this challenge, it is necessary to use high performance computing (HPC) platforms and techniques. However, the development of an integrated HPC system that makes efficient use of its elements is not trivial. We have developed an application termed DOVIS that uses AutoDock (version 3) as the docking engine and runs in parallel on a Linux cluster. DOVIS can efficiently dock large numbers (millions) of small molecules (ligands) to a receptor, screening 500 to 1,000 compounds per processor per day. Furthermore, in DOVIS, the docking session is fully integrated and automated in that the inputs are specified via a graphical user interface, the calculations are fully integrated with a Linux cluster queuing system for parallel processing, and the results can be visualized and queried. DOVIS removes most of the complexities and organizational problems associated with large-scale high-throughput virtual screening, and provides a convenient and efficient solution for AutoDock users to use this software in a Linux cluster platform.

System and Method for Automated Rendezvous, Docking and Capture of Autonomous Underwater Vehicles

NASA Technical Reports Server (NTRS)

Clark, Evan (Inventor); Richmond, Kristof (Inventor); Paulus, Jeremy (Inventor); Kimball, Peter (Inventor); Scully, Mark (Inventor); Kapit, Jason (Inventor); Stone, William C. (Inventor)

2018-01-01

A system for automated rendezvous, docking, and capture of autonomous underwater vehicles at the conclusion of a mission comprising of comprised of a docking rod having lighted, pulsating (in both frequency and light intensity) series of LED light strips thereon, with the LEDs at a known spacing, and the autonomous underwater vehicle specially designed to detect and capture the docking rod and then be lifted structurally by a spherical end strop about which the vehicle can be pivoted and hoisted up (e.g., onto a ship). The method of recovery allows for very routine and reliable automated recovery of an unmanned underwater asset.

Interaction of new kinase inhibitors cabozantinib and tofacitinib with human serum alpha-1 acid glycoprotein. A comprehensive spectroscopic and molecular Docking approach

NASA Astrophysics Data System (ADS)

Ajmal, Mohammad Rehan; Abdelhameed, Ali Saber; Alam, Parvez; Khan, Rizwan Hasan

2016-04-01

In the current study we have investigated the interaction of newly approved kinase inhibitors namely Cabozantinib (CBZ) and Tofacitinib (TFB) with human Alpha-1 acid glycoprotein (AAG) under simulated physiological conditions using fluorescence quenching measurements, circular dichroism, dynamic light scattering and molecular docking methods. CBZ and TFB binds to AAG with significant affinity and the calculated binding constant for the drugs lie in the order of 104. With the increase in temperature the binding constant values decreased for both CBZ and TFB. The fluorescence resonance energy transfer (FRET) from AAG to CBZ and TFB suggested the fluorescence intensity of AAG was quenched by the two studied drugs via the formation of a non-fluorescent complex in the static manner. The molecular distance r value calculated from FRET is around 2 nm for both drugs, fluorescence spectroscopy data was employed for the study of thermodynamic parameters, standard Gibbs free energy change at 300K was calculated as - 5.234 kcal mol- 1 for CBZ-AAG interaction and - 6.237 kcal mol- 1 for TFB-AAG interaction, standard enthalpy change and standard entropy change for CBZ-AAG interaction are - 9.553 kcal mol- 1 and - 14.618 cal mol- 1K- 1 respectively while for AAG-TFB interaction, standard enthalpy and standard entropy change was calculated as 4.019 kcal mol- 1 and 7.206 cal mol- 1K- 1 respectively. Protein binding of the two drugs caused the tertiary structure alterations. Dynamic light scattering measurements demonstrated the reduction in the hydrodynamic radii of the protein. Furthermore molecular docking results suggested the Hydrophobic interaction and hydrogen bonding were the interactive forces in the binding process of CBZ to AAG while in case of TFB only hydrophobic interactions were found to be involved, overlap of the binding site for two studied drugs on the AAG molecule was revealed by docking results.

An Automated Strategy for Binding-Pose Selection and Docking Assessment in Structure-Based Drug Design.

PubMed

Ballante, Flavio; Marshall, Garland R

2016-01-25

Molecular docking is a widely used technique in drug design to predict the binding pose of a candidate compound in a defined therapeutic target. Numerous docking protocols are available, each characterized by different search methods and scoring functions, thus providing variable predictive capability on a same ligand-protein system. To validate a docking protocol, it is necessary to determine a priori the ability to reproduce the experimental binding pose (i.e., by determining the docking accuracy (DA)) in order to select the most appropriate docking procedure and thus estimate the rate of success in docking novel compounds. As common docking programs use generally different root-mean-square deviation (RMSD) formulas, scoring functions, and format results, it is both difficult and time-consuming to consistently determine and compare their predictive capabilities in order to identify the best protocol to use for the target of interest and to extrapolate the binding poses (i.e., best-docked (BD), best-cluster (BC), and best-fit (BF) poses) when applying a given docking program over thousands/millions of molecules during virtual screening. To reduce this difficulty, two new procedures called Clusterizer and DockAccessor have been developed and implemented for use with some common and "free-for-academics" programs such as AutoDock4, AutoDock4(Zn), AutoDock Vina, DOCK, MpSDockZn, PLANTS, and Surflex-Dock to automatically extrapolate BD, BC, and BF poses as well as to perform consistent cluster and DA analyses. Clusterizer and DockAccessor (code available over the Internet) represent two novel tools to collect computationally determined poses and detect the most predictive docking approach. Herein an application to human lysine deacetylase (hKDAC) inhibitors is illustrated.

Docking system for spacecraft

NASA Technical Reports Server (NTRS)

Kahn, Jon B. (Inventor)

1988-01-01

A mechanism is disclosed for the docking of a spacecraft to a space station where a connection for transfer of personnel and equipment is desired. The invention comprises an active docking structure on a spacecraft and a passive docking structure on the station. The passive structure includes a docking ring mounted on a tunnel structure fixed to the space station. The active structure includes a docking ring carried by an actuator-attenuator devices, each attached at one end to the ring and at its other end in the spacecraft payload bay. The devices respond to command signals for moving the docking ring between a stowed position in the spacecraft to a deployed position suitable for engagement with the docking ring. The devices comprise means responsive to signals of sensed loadings to absorb impact energy and retraction means for drawing the coupled spacecraft and station into final docked configuration and moving the tunnel structure to a berthed position in the spacecraft. Latches couple the spacecraft and space station upon contact of the docking rings and latches establish a structural tie between the spacecraft when retracted.

Synthesis, evaluation and molecular docking studies of amino acid derived N-glycoconjugates as antibacterial agents.

PubMed

Baig, Noorullah; Singh, Rajnish Prakash; Chander, Subhash; Jha, Prabhat Nath; Murugesan, Sankaranarayanan; Sah, Ajay K

2015-12-01

Six amino acid derived N-glycoconjugates of d-glucose were synthesized, characterized and tested for antibacterial activity against G(+)ve (Bacillus cereus) as well as G(-)ve (Escherichia coli and Klebsiella pneumoniae) bacterial strains. All the tested compounds exhibited moderate to good antibacterial activity against these bacterial strains. The results were compared with the antibacterial activity of standard drug Chloramphenicol, where results of A5 (Tryptophan derived glycoconjugates) against E. coli and A4 (Isoleucine derived glycoconjugates) against K. pneumoniae bacterial strains are comparable with the standard drug molecule. In silico docking studies were also performed in order to understand the mode of action and binding interactions of these molecules. The docking studies revealed that, occupation of compound A5 at the ATP binding site of subunit GyrB (DNA gyrase, PDB ID: 3TTZ) via hydrophobic and hydrogen bonding interactions may be the reason for its significant in vitro antibacterial activity. Copyright © 2015 Elsevier Inc. All rights reserved.

GRC-2009-C-01749

NASA Image and Video Library

2005-07-01

Photographs of the Low Impact Docking System (LIDS); this hardware is a test for the ORION docking birthing system to connect the Crew Exploration Vehicle (CEV) to the International Space Station (ISS); atomic oxygen 12 inch seals testing

Meteoroid and Orbital Debris Threats to NASA's Docking Seals: Initial Assessment and Methodology

NASA Technical Reports Server (NTRS)

deGroh, Henry C., III; Nahra, Henry K.

2009-01-01

The Crew Exploration Vehicle (CEV) will be exposed to the Micrometeoroid Orbital Debris (MMOD) environment in Low Earth Orbit (LEO) during missions to the International Space Station (ISS) and to the micrometeoroid environment during lunar missions. The CEV will be equipped with a docking system which enables it to connect to ISS and the lunar module known as Altair; this docking system includes a hatch that opens so crew and supplies can pass between the spacecrafts. This docking system is known as the Low Impact Docking System (LIDS) and uses a silicone rubber seal to seal in cabin air. The rubber seal on LIDS presses against a metal flange on ISS (or Altair). All of these mating surfaces are exposed to the space environment prior to docking. The effects of atomic oxygen, ultraviolet and ionizing radiation, and MMOD have been estimated using ground based facilities. This work presents an initial methodology to predict meteoroid and orbital debris threats to candidate docking seals being considered for LIDS. The methodology integrates the results of ground based hypervelocity impacts on silicone rubber seals and aluminum sheets, risk assessments of the MMOD environment for a variety of mission scenarios, and candidate failure criteria. The experimental effort that addressed the effects of projectile incidence angle, speed, mass, and density, relations between projectile size and resulting crater size, and relations between crater size and the leak rate of candidate seals has culminated in a definition of the seal/flange failure criteria. The risk assessment performed with the BUMPER code used the failure criteria to determine the probability of failure of the seal/flange system and compared the risk to the allotted risk dictated by NASA's program requirements.

Meteoroid and Orbital Debris Threats to NASA's Docking Seals: Initial Assessment and Methodology

NASA Technical Reports Server (NTRS)

deGroh, Henry C., III; Gallo, Christopher A.; Nahra, Henry K.

2009-01-01

The Crew Exploration Vehicle (CEV) will be exposed to the Micrometeoroid Orbital Debris (MMOD) environment in Low Earth Orbit (LEO) during missions to the International Space Station (ISS) and to the micrometeoroid environment during lunar missions. The CEV will be equipped with a docking system which enables it to connect to ISS and the lunar module known as Altair; this docking system includes a hatch that opens so crew and supplies can pass between the spacecrafts. This docking system is known as the Low Impact Docking System (LIDS) and uses a silicone rubber seal to seal in cabin air. The rubber seal on LIDS presses against a metal flange on ISS (or Altair). All of these mating surfaces are exposed to the space environment prior to docking. The effects of atomic oxygen, ultraviolet and ionizing radiation, and MMOD have been estimated using ground based facilities. This work presents an initial methodology to predict meteoroid and orbital debris threats to candidate docking seals being considered for LIDS. The methodology integrates the results of ground based hypervelocity impacts on silicone rubber seals and aluminum sheets, risk assessments of the MMOD environment for a variety of mission scenarios, and candidate failure criteria. The experimental effort that addressed the effects of projectile incidence angle, speed, mass, and density, relations between projectile size and resulting crater size, and relations between crater size and the leak rate of candidate seals has culminated in a definition of the seal/flange failure criteria. The risk assessment performed with the BUMPER code used the failure criteria to determine the probability of failure of the seal/flange system and compared the risk to the allotted risk dictated by NASA s program requirements.

Lacosamide derivatives with anticonvulsant activity as carbonic anhydrase inhibitors. Molecular modeling, docking and QSAR analysis.

PubMed

Garro Martinez, Juan C; Vega-Hissi, Esteban G; Andrada, Matías F; Duchowicz, Pablo R; Torrens, Francisco; Estrada, Mario R

2014-01-01

Lacosamide is an anticonvulsant drug which presents carbonic anhydrase inhibition. In this paper, we analyzed the apparent relationship between both activities performing a molecular modeling, docking and QSAR studies on 18 lacosamide derivatives with known anticonvulsant activity. Docking results suggested the zinc-binding site of carbonic anhydrase is a possible target of lacosamide and lacosamide derivatives making favorable Van der Waals interactions with Asn67, Gln92, Phe131 and Thr200. The mathematical models revealed a poor relationship between the anticonvulsant activity and molecular descriptors obtained from DFT and docking calculations. However, a QSAR model was developed using Dragon software descriptors. The statistic parameters of the model are: correlation coefficient, R=0.957 and standard deviation, S=0.162. Our results provide new valuable information regarding the relationship between both activities and contribute important insights into the essential molecular requirements for the anticonvulsant activity.

Casual Dock Work: Profile of Diseases and Injuries and Perception of Influence on Health

PubMed Central

Cezar-Vaz, Marta Regina; de Almeida, Marlise Capa Verde; Bonow, Clarice Alves; Rocha, Laurelize Pereira; Borges, Anelise Miritz; Piexak, Diéssica Roggia

2014-01-01

The present study aimed to identify the profile of diseases and injuries that affect casual dock workers and identify casual dock workers’ perceptions of positive and negative work influences on their health. This study consisted of two phases. The first phase was a quantitative study composed of a retrospective analysis, conducted with 953 medical records. The second phase of the research is a non-random sample with 51 casual dock workers. Data analysis was performed with SPSS 19.0. The average age of the casual dock workers was 48.7. Concerning working time, the majority had more than 19.6 years of dock work experience. In the first phase, 527 pathologic diagnoses were identified. The diagnoses that affected the musculoskeletal system (15.8%, N = 152; p < 0.01) were highlighted. Consequences to physical health produced by accidents stood out, with fracture registration predominating (12.8%, N = 122; p < 0.05). Significant differences were found for positive work influence on the cardiovascular system and family health. It was concluded that the diagnoses obtained are related to the influence of dock work perception and have motivated an introduction of preventive measures. PMID:24557521

Orbiter Docking System Installation

NASA Technical Reports Server (NTRS)

1995-01-01

Workers in Orbiter Processing Facility Bay 3 are installing the Orbiter Docking System (ODS) in the payload bay of the orbiter Atlantis (OV-104). The ODS includes an airlock, a supporting truss structure, a docking base, and a Russian-built docking mechanism (uppermost). The ODS is nearly 15 feet (4.6 meters) wide, 6.5 feet (2 meters) long, 13.5 feet (4.1 meters high), and weighs more than 3,500 pounds (1,588 kilograms). It is being installed near the forward end of the orbiter's payload bay and will be connected by a short tunnel to the existing airlock inside the orbiter's pressurized crew cabin.The installation will take about two hours to complete. Later this week, the Spacelab module also will be installed in OV-104's payload bay; it will connect to the ODS via a tunnel. During the first docking between the Space Shuttle Atlantis and the Russian Space Station Mir, the Russian-built docking mechanism on the ODS will be mated to a similar interface on the Krystall module docking port on Mir, allowing crew members to pass back and forth between the two spacecraft. That Shuttle mission, STS-71, is scheduled for liftoff in early June.

Port positioning and docking for single-stage totally robotic dissection for rectal cancer surgery with the Si and Xi Da Vinci Surgical System.

PubMed

Toh, James Wei Tatt; Kim, Seon-Hahn

2017-11-04

We have previously reported our technique of single-docking totally robotic dissection for rectal cancer surgery using the Da Vinci ® Si Surgical System in 2009. However, we have since optimised our port placement for the Si system and have developed a novel configuration of port placement and docking for the Da Vinci ® Xi Surgical System. We have performed over 700 cases using this technique with the Si system and have used our Xi technique since 2016 for totally robotic dissection for rectal cancer. We have kept the configuration of port placements for both the Xi and Si system as similar as possible, with the priorities to avoid arm collisions as well as to provide a workable port configuration of two left-handed instruments and one right-handed instrument. To date, there have had no major complications or arm collisions related to this technique of docking, port positioning and instrument placement.

Autonomous docking ground demonstration

NASA Technical Reports Server (NTRS)

Lamkin, Steve L.; Le, Thomas Quan; Othon, L. T.; Prather, Joseph L.; Eick, Richard E.; Baxter, Jim M.; Boyd, M. G.; Clark, Fred D.; Spehar, Peter T.; Teters, Rebecca T.

1991-01-01

The Autonomous Docking Ground Demonstration is an evaluation of the laser sensor system to support the docking phase (12 ft to contact) when operated in conjunction with the guidance, navigation, and control (GN&C) software. The docking mechanism being used was developed for the Apollo/Soyuz Test Program. This demonstration will be conducted using the 6-DOF Dynamic Test System (DTS). The DTS simulates the Space Station Freedom as the stationary or target vehicle and the Orbiter as the active or chase vehicle. For this demonstration, the laser sensor will be mounted on the target vehicle and the retroflectors will be on the chase vehicle. This arrangement was chosen to prevent potential damage to the laser. The laser sensor system, GN&C, and 6-DOF DTS will be operated closed-loop. Initial conditions to simulate vehicle misalignments, translational and rotational, will be introduced within the constraints of the systems involved.

Orbiter Docking System/Spacelab-Mir Module in Atlantis

NASA Technical Reports Server (NTRS)

1995-01-01

The STS-71 mission payload is in its final flight configuration after integration into the payload bay of the Space Shuttle orbiter Atlantis and prior to payload bay door closing and rollover of the spaceplane from Orbiter Processing Facility Bay 3 to the Vehicle Assembly Building. In the foreground is the Orbiter Docking System (ODS) that is topped with the red Russian- built Androgynous Peripheral Docking System (APDS). During the 11-day mission, the APDS will lock together with a similar system on the Russian Mir Space Station so that the two spacecraft can remain docked together for four days. The ODS features an airlock that will provide access to and from both the Mir and orbiter for the U.S. and Russian flight crews. A Spacelab transfer tunnel runs from the ODS to the Spacelab-Mir module, where joint U.S. medical experiments will be conducted during the 11-day spaceflight.

Novel Penicillin Analogues as Potential Antimicrobial Agents; Design, Synthesis and Docking Studies.

PubMed

Ashraf, Zaman; Bais, Abdul; Manir, Md Maniruzzaman; Niazi, Umar

2015-01-01

A number of penicillin derivatives (4a-h) were synthesized by the condensation of 6-amino penicillinic acid (6-APA) with non-steroidal anti-inflammatory drugs as antimicrobial agents. In silico docking study of these analogues was performed against Penicillin Binding Protein (PDBID 1CEF) using AutoDock Tools 1.5.6 in order to investigate the antimicrobial data on structural basis. Penicillin binding proteins function as either transpeptidases or carboxypeptidases and in few cases demonstrate transglycosylase activity in bacteria. The excellent antibacterial potential was depicted by compounds 4c and 4e against Escherichia coli, Staphylococcus epidermidus and Staphylococcus aureus compared to the standard amoxicillin. The most potent penicillin derivative 4e exhibited same activity as standard amoxicillin against S. aureus. In the enzyme inhibitory assay the compound 4e inhibited E. coli MurC with an IC50 value of 12.5 μM. The docking scores of these compounds 4c and 4e also verified their greater antibacterial potential. The results verified the importance of side chain functionalities along with the presence of central penam nucleus. The binding affinities calculated from docking results expressed in the form of binding energies ranges from -7.8 to -9.2kcal/mol. The carboxylic group of penam nucleus in all these compounds is responsible for strong binding with receptor protein with the bond length ranges from 3.4 to 4.4 Ǻ. The results of present work ratify that derivatives 4c and 4e may serve as a structural template for the design and development of potent antimicrobial agents.

Novel Penicillin Analogues as Potential Antimicrobial Agents; Design, Synthesis and Docking Studies

PubMed Central

Ashraf, Zaman; Bais, Abdul; Manir, Md. Maniruzzaman; Niazi, Umar

2015-01-01

A number of penicillin derivatives (4a-h) were synthesized by the condensation of 6-amino penicillinic acid (6-APA) with non-steroidal anti-inflammatory drugs as antimicrobial agents. In silico docking study of these analogues was performed against Penicillin Binding Protein (PDBID 1CEF) using AutoDock Tools 1.5.6 in order to investigate the antimicrobial data on structural basis. Penicillin binding proteins function as either transpeptidases or carboxypeptidases and in few cases demonstrate transglycosylase activity in bacteria. The excellent antibacterial potential was depicted by compounds 4c and 4e against Escherichia coli, Staphylococcus epidermidus and Staphylococcus aureus compared to the standard amoxicillin. The most potent penicillin derivative 4e exhibited same activity as standard amoxicillin against S. aureus. In the enzyme inhibitory assay the compound 4e inhibited E. coli MurC with an IC50 value of 12.5 μM. The docking scores of these compounds 4c and 4e also verified their greater antibacterial potential. The results verified the importance of side chain functionalities along with the presence of central penam nucleus. The binding affinities calculated from docking results expressed in the form of binding energies ranges from -7.8 to -9.2kcal/mol. The carboxylic group of penam nucleus in all these compounds is responsible for strong binding with receptor protein with the bond length ranges from 3.4 to 4.4 Ǻ. The results of present work ratify that derivatives 4c and 4e may serve as a structural template for the design and development of potent antimicrobial agents. PMID:26267242

STS-89 tunnel adapter in OPF bay 1

NASA Technical Reports Server (NTRS)

1997-01-01

The tunnel adapter (left) which will be flown on the STS-89 mission is being installed in the Space Shuttle orbiter Endeavour's payload bay in Orbiter Processing Facility bay 1. To the right is the Orbiter Docking System (ODS), with its distinctive red Russian-built Androgynous Peripheral Docking System (APDS). STS-89 will be the eighth U.S. docking mission with the Russian Mir space station. The nine-day space flight is scheduled for launch in mid-January 1998.

Synthesis, anti-inflammatory evaluation and docking studies of some new fluorinated fused quinazolines.

PubMed

Balakumar, C; Lamba, P; Kishore, D Pran; Narayana, B Lakshmi; Rao, K Venkat; Rajwinder, K; Rao, A Raghuram; Shireesha, B; Narsaiah, B

2010-11-01

A series of novel 8/10-trifluoromethyl-substituted-imidazo[1,2-c] quinazolines have been synthesized and evaluated in vivo (rat paw edema) for their anti-inflammatory activity and in silico (docking studies) to recognize the hypothetical binding motif of the title compounds with the cyclooxygenase isoenzymes (COX-1 and COX-2) employing GOLD (CCDC, 4.0.1 version) software. The compounds, 9b and 10b, were found to have good anti-inflammatory activity [around 80% of the standard: indomethacin]. The binding mode of the title compounds has been proposed based on the docking studies. Crown Copyright © 2010. Published by Elsevier Masson SAS. All rights reserved.

Environmental Assessment: Replacement of Subscale Drone Recovery Boat Dock at Tyndall Air Force Base, Florida

DTIC Science & Technology

2009-12-01

Jefferson Davis Highway, Suite 1204, Arlington VA 22202-4302. Respondents should be aware that notwithstanding any other provision of law, no person ...90 19a. NAME OF RESPONSIBLE PERSON a. REPORT unclassified b. ABSTRACT unclassified c. THIS PAGE unclassified Standard Form 298 (Rev. 8-98...Prescribed by ANSI Std Z39-18 Final Finding of No Significant Impact for Construction and Operation of an Alternate Drone Launch System at Tyndall

Automatic rendezvous and docking systems functional and performance requirements

NASA Technical Reports Server (NTRS)

1985-01-01

A generalized mission design scheme which utilizes a standard mission profile for all OMV rendezvous operations, recognizes typical operational constraints, and minimizes propellant penalties due to nodal regression effects was developed. This scheme has been used to demonstrate a unified guidance and navigation maneuver processor (the UMP), which supports all mission phases through station-keeping. The initial demonstration version of the Orbital Rendezvous Mission Planner (ORMP) was provided for evaluation purposes, and program operation was discussed.

An Efficient Implementation of the Nwat-MMGBSA Method to Rescore Docking Results in Medium-Throughput Virtual Screenings

NASA Astrophysics Data System (ADS)

Maffucci, Irene; Hu, Xiao; Fumagalli, Valentina; Contini, Alessandro

2018-03-01

Nwat-MMGBSA is a variant of MM-PB/GBSA based on the inclusion of a number of explicit water molecules that are the closest to the ligand in each frame of a molecular dynamics trajectory. This method demonstrated improved correlations between calculated and experimental binding energies in both protein-protein interactions and ligand-receptor complexes, in comparison to the standard MM-GBSA. A protocol optimization, aimed to maximize efficacy and efficiency, is discussed here considering penicillopepsin, HIV1-protease, and BCL-XL as test cases. Calculations were performed in triplicates on both classic HPC environments and on standard workstations equipped by a GPU card, evidencing no statistical differences in the results. No relevant differences in correlation to experiments were also observed when performing Nwat-MMGBSA calculations on 4 ns or 1 ns long trajectories. A fully automatic workflow for structure-based virtual screening, performing from library set-up to docking and Nwat-MMGBSA rescoring, has then been developed. The protocol has been tested against no rescoring or standard MM-GBSA rescoring within a retrospective virtual screening of inhibitors of AmpC β-lactamase and of the Rac1-Tiam1 protein-protein interaction. In both cases, Nwat-MMGBSA rescoring provided a statistically significant increase in the ROC AUCs of between 20% and 30%, compared to docking scoring or to standard MM-GBSA rescoring.

Cosolvent-Based Molecular Dynamics for Ensemble Docking: Practical Method for Generating Druggable Protein Conformations.

PubMed

Uehara, Shota; Tanaka, Shigenori

2017-04-24

Protein flexibility is a major hurdle in current structure-based virtual screening (VS). In spite of the recent advances in high-performance computing, protein-ligand docking methods still demand tremendous computational cost to take into account the full degree of protein flexibility. In this context, ensemble docking has proven its utility and efficiency for VS studies, but it still needs a rational and efficient method to select and/or generate multiple protein conformations. Molecular dynamics (MD) simulations are useful to produce distinct protein conformations without abundant experimental structures. In this study, we present a novel strategy that makes use of cosolvent-based molecular dynamics (CMD) simulations for ensemble docking. By mixing small organic molecules into a solvent, CMD can stimulate dynamic protein motions and induce partial conformational changes of binding pocket residues appropriate for the binding of diverse ligands. The present method has been applied to six diverse target proteins and assessed by VS experiments using many actives and decoys of DEKOIS 2.0. The simulation results have revealed that the CMD is beneficial for ensemble docking. Utilizing cosolvent simulation allows the generation of druggable protein conformations, improving the VS performance compared with the use of a single experimental structure or ensemble docking by standard MD with pure water as the solvent.

PyGOLD: a python based API for docking based virtual screening workflow generation.

PubMed

Patel, Hitesh; Brinkjost, Tobias; Koch, Oliver

2017-08-15

Molecular docking is one of the successful approaches in structure based discovery and development of bioactive molecules in chemical biology and medicinal chemistry. Due to the huge amount of computational time that is still required, docking is often the last step in a virtual screening approach. Such screenings are set as workflows spanned over many steps, each aiming at different filtering task. These workflows can be automatized in large parts using python based toolkits except for docking using the docking software GOLD. However, within an automated virtual screening workflow it is not feasible to use the GUI in between every step to change the GOLD configuration file. Thus, a python module called PyGOLD was developed, to parse, edit and write the GOLD configuration file and to automate docking based virtual screening workflows. The latest version of PyGOLD, its documentation and example scripts are available at: http://www.ccb.tu-dortmund.de/koch or http://www.agkoch.de. PyGOLD is implemented in Python and can be imported as a standard python module without any further dependencies. oliver.koch@agkoch.de, oliver.koch@tu-dortmund.de. Supplementary data are available at Bioinformatics online. © The Author (2017). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Docking system for spacecraft

NASA Technical Reports Server (NTRS)

Kahn, Jon B. (Inventor)

1990-01-01

A mechanism for the docking of a space vehicle to a space station where a connection for transfer of personnel and equipment is desired. The invention comprises an active docking structure on a space vehicle 10 and a passive docking structure on a station 11. The passive structure includes a docking ring 50 mounted on a tunnel structure 35 fixed to the space station. The active structure including a docking ring 18 carried by actuator-attenuator devices 20, each attached at one end to the ring 18 and at its other end in the vehicle's payload bay 12. The devices 20 respond to command signals for moving the docking ring 18 between a stowed position in the space vehicle to a deployed position suitable for engagement with the docking ring 50. The devices 20 comprise means responsive to signals of sensed loadings to absorb impact energy and retraction means for drawing the coupled space vehicle and station into final docked configuration and moving the tunnel structure to a berthed position in the space vehicle 10. Latches 60 couple the space vehicle and space station upon contact of docking rings 18 and 50 and latches 41-48 establish a structural tie between the spacecraft when retracted.

GPU.proton.DOCK: Genuine Protein Ultrafast proton equilibria consistent DOCKing.

PubMed

Kantardjiev, Alexander A

2011-07-01

GPU.proton.DOCK (Genuine Protein Ultrafast proton equilibria consistent DOCKing) is a state of the art service for in silico prediction of protein-protein interactions via rigorous and ultrafast docking code. It is unique in providing stringent account of electrostatic interactions self-consistency and proton equilibria mutual effects of docking partners. GPU.proton.DOCK is the first server offering such a crucial supplement to protein docking algorithms--a step toward more reliable and high accuracy docking results. The code (especially the Fast Fourier Transform bottleneck and electrostatic fields computation) is parallelized to run on a GPU supercomputer. The high performance will be of use for large-scale structural bioinformatics and systems biology projects, thus bridging physics of the interactions with analysis of molecular networks. We propose workflows for exploring in silico charge mutagenesis effects. Special emphasis is given to the interface-intuitive and user-friendly. The input is comprised of the atomic coordinate files in PDB format. The advanced user is provided with a special input section for addition of non-polypeptide charges, extra ionogenic groups with intrinsic pK(a) values or fixed ions. The output is comprised of docked complexes in PDB format as well as interactive visualization in a molecular viewer. GPU.proton.DOCK server can be accessed at http://gpudock.orgchm.bas.bg/.

Autonomous docking system for space structures and satellites

NASA Astrophysics Data System (ADS)

Prasad, Guru; Tajudeen, Eddie; Spenser, James

2005-05-01

Aximetric proposes Distributed Command and Control (C2) architecture for autonomous on-orbit assembly in space with our unique vision and sensor driven docking mechanism. Aximetric is currently working on ip based distributed control strategies, docking/mating plate, alignment and latching mechanism, umbilical structure/cord designs, and hardware/software in a closed loop architecture for smart autonomous demonstration utilizing proven developments in sensor and docking technology. These technologies can be effectively applied to many transferring/conveying and on-orbit servicing applications to include the capturing and coupling of space bound vehicles and components. The autonomous system will be a "smart" system that will incorporate a vision system used for identifying, tracking, locating and mating the transferring device to the receiving device. A robustly designed coupler for the transfer of the fuel will be integrated. Advanced sealing technology will be utilized for isolation and purging of resulting cavities from the mating process and/or from the incorporation of other electrical and data acquisition devices used as part of the overall smart system.

Implementation of the Hungarian Algorithm to Account for Ligand Symmetry and Similarity in Structure-Based Design

PubMed Central

2015-01-01

False negative docking outcomes for highly symmetric molecules are a barrier to the accurate evaluation of docking programs, scoring functions, and protocols. This work describes an implementation of a symmetry-corrected root-mean-square deviation (RMSD) method into the program DOCK based on the Hungarian algorithm for solving the minimum assignment problem, which dynamically assigns atom correspondence in molecules with symmetry. The algorithm adds only a trivial amount of computation time to the RMSD calculations and is shown to increase the reported overall docking success rate by approximately 5% when tested over 1043 receptor–ligand systems. For some families of protein systems the results are even more dramatic, with success rate increases up to 16.7%. Several additional applications of the method are also presented including as a pairwise similarity metric to compare molecules during de novo design, as a scoring function to rank-order virtual screening results, and for the analysis of trajectories from molecular dynamics simulation. The new method, including source code, is available to registered users of DOCK6 (http://dock.compbio.ucsf.edu). PMID:24410429

Development of an autonomous video rendezous and docking system

NASA Technical Reports Server (NTRS)

Tietz, J. C.; Kelly, J. H.

1982-01-01

Video control systems using three flashing lights and two other types of docking aids were evaluated through computer simulation and other approaches. The three light system performed much better than the others. Its accuracy is affected little by tumbling of the target spacecraft, and in the simulations it was able to cope with attitude rates up to 20,000 degrees per hour about the docking axis. Its performance with rotation about other axes is determined primarily by the state estimation and goal setting portions of the control system, not by measurement accuracy. A suitable control system, and a computer program that can serve as the basis for the physical simulation are discussed.

Technical Note: Mobile accelerator guidance using an optical tracker during docking in IOERT procedures.

PubMed

Marinetto, Eugenio; Victores, Juan González; García-Sevilla, Mónica; Muñoz, Mercedes; Calvo, Felipe Ángel; Balaguer, Carlos; Desco, Manuel; Pascau, Javier

2017-10-01

Intraoperative electron radiation therapy (IOERT) involves the delivery of a high radiation dose during tumor resection in a shorter time than other radiation techniques, thus improving local control of tumors. However, a linear accelerator device is needed to produce the beam safely. Mobile linear accelerators have been designed as dedicated units that can be moved into the operating room and deliver radiation in situ. Correct and safe dose delivery is a key concern when using mobile accelerators. The applicator is commonly fixed to the patient's bed to ensure that the dose is delivered to the prescribed location, and the mobile accelerator is moved to dock the applicator to the radiation beam output (gantry). In a typical clinical set-up, this task is time-consuming because of safety requirements and the limited degree of freedom of the gantry. The objective of this study was to present a navigation solution based on optical tracking for guidance of docking to improve safety and reduce procedure time. We used an optical tracker attached to the mobile linear accelerator to track the prescribed localization of the radiation collimator inside the operating room. Using this information, the integrated navigation system developed computes the movements that the mobile linear accelerator needs to perform to align the applicator and the radiation gantry and warns the physician if docking is unrealizable according to the available degrees of freedom of the mobile linear accelerator. Furthermore, we coded a software application that connects all the necessary functioning elements and provides a user interface for the system calibration and the docking guidance. The system could safeguard against the spatial limitations of the operating room, calculate the optimal arrangement of the accelerator and reduce the docking time in computer simulations and experimental setups. The system could be used to guide docking with any commercial linear accelerator. We believe that the docking navigator we present is a major contribution to IOERT, where docking is critical when attempting to reduce surgical time, ensure patient safety and guarantee that the treatment administered follows the radiation oncologist's prescription. © 2017 American Association of Physicists in Medicine.

Apollo Soyuz test project. USA-USSR, fact sheet

NASA Technical Reports Server (NTRS)

1974-01-01

The Apollo Soyuz Test Project (ASTP) is discussed. The United States and the Soviet Union have agreed to develop compatible rendezvous and docking systems which will provide a basis for docking and rescue on future spacecraft of both nations. The ASTP mission will include testing the rendezvous system in orbit, verifying techniques for transfer of astronauts and cosmonauts, and conducting experiments while docked and undocked. Diagrams of the spacecraft and systems involved in the tests are presented. The prime contractors for the equipment are identified. Biographical data on the astronauts participating in the program are provided.

GEMINI-TITAN (GT)-11 - EARTH - SKY - DOCKING - OUTER SPACE

NASA Image and Video Library

1966-07-18

S66-46144 (18 July 1966) --- The Gemini-10 spacecraft is successfully docked with the Agena Target Docking Vehicle 5005. The Agena display panel is clearly visible. After docking with the Agena, astronauts John W. Young, command pilot, and Michael Collins, pilot, fired the 16,000-pound thrust engine of Agena-10's primary propulsion system to boost the combined vehicles into an orbit with an apogee of 413 nautical miles to set a new altitude record for manned spaceflight. Photo credit: NASA

Multibody dynamical modeling for spacecraft docking process with spring-damper buffering device: A new validation approach

NASA Astrophysics Data System (ADS)

Daneshjou, Kamran; Alibakhshi, Reza

2018-01-01

In the current manuscript, the process of spacecraft docking, as one of the main risky operations in an on-orbit servicing mission, is modeled based on unconstrained multibody dynamics. The spring-damper buffering device is utilized here in the docking probe-cone system for micro-satellites. Owing to the impact occurs inevitably during docking process and the motion characteristics of multibody systems are remarkably affected by this phenomenon, a continuous contact force model needs to be considered. Spring-damper buffering device, keeping the spacecraft stable in an orbit when impact occurs, connects a base (cylinder) inserted in the chaser satellite and the end of docking probe. Furthermore, by considering a revolute joint equipped with torsional shock absorber, between base and chaser satellite, the docking probe can experience both translational and rotational motions simultaneously. Although spacecraft docking process accompanied by the buffering mechanisms may be modeled by constrained multibody dynamics, this paper deals with a simple and efficient formulation to eliminate the surplus generalized coordinates and solve the impact docking problem based on unconstrained Lagrangian mechanics. By an example problem, first, model verification is accomplished by comparing the computed results with those recently reported in the literature. Second, according to a new alternative validation approach, which is based on constrained multibody problem, the accuracy of presented model can be also evaluated. This proposed verification approach can be applied to indirectly solve the constrained multibody problems by minimum required effort. The time history of impact force, the influence of system flexibility and physical interaction between shock absorber and penetration depth caused by impact are the issues followed in this paper. Third, the MATLAB/SIMULINK multibody dynamic analysis software will be applied to build impact docking model to validate computed results and then, investigate the trajectories of both satellites to take place the successful capture process.

Machine Vision for Relative Spacecraft Navigation During Approach to Docking

NASA Technical Reports Server (NTRS)

Chien, Chiun-Hong; Baker, Kenneth

2011-01-01

This paper describes a machine vision system for relative spacecraft navigation during the terminal phase of approach to docking that: 1) matches high contrast image features of the target vehicle, as seen by a camera that is bore-sighted to the docking adapter on the chase vehicle, to the corresponding features in a 3d model of the docking adapter on the target vehicle and 2) is robust to on-orbit lighting. An implementation is provided for the case of the Space Shuttle Orbiter docking to the International Space Station (ISS) with quantitative test results using a full scale, medium fidelity mock-up of the ISS docking adapter mounted on a 6-DOF motion platform at the NASA Marshall Spaceflight Center Flight Robotics Laboratory and qualitative test results using recorded video from the Orbiter Docking System Camera (ODSC) during multiple orbiter to ISS docking missions. The Natural Feature Image Registration (NFIR) system consists of two modules: 1) Tracking which tracks the target object from image to image and estimates the position and orientation (pose) of the docking camera relative to the target object and 2) Acquisition which recognizes the target object if it is in the docking camera Field-of-View and provides an approximate pose that is used to initialize tracking. Detected image edges are matched to the 3d model edges whose predicted location, based on the pose estimate and its first time derivative from the previous frame, is closest to the detected edge1 . Mismatches are eliminated using a rigid motion constraint. The remaining 2d image to 3d model matches are used to make a least squares estimate of the change in relative pose from the previous image to the current image. The changes in position and in attitude are used as data for two Kalman filters whose outputs are smoothed estimate of position and velocity plus attitude and attitude rate that are then used to predict the location of the 3d model features in the next image.

Saturn Apollo Program

NASA Image and Video Library

1974-06-01

This illustration shows the docking configuration of the Apollo-Soyuz Test Project (ASTP). The ASTP was the first international docking of the U.S.'s Apollo spacecraft and the U.S.S.R.'s Soyuz spacecraft in space. A joint engineering team from the two countries met to develop a docking system that permitted the two spacecraft to link in space and allowed the two crews to travel from one spacecraft to the other. This system entailed developing a large habitable Docking Module (DM) to be carried on the Apollo spacecraft to facilitate the joining of two dissimilar spacecraft. The Marshall Space Flight Center was responsible for development and sustaining engineering of the Saturn IB launch vehicle during the mission. The ASTP marked the last use of the Saturn Launch Vehicle.

Focused library design and synthesis of 2-mercapto benzothiazole linked 1,2,4-oxadiazoles as COX-2/5-LOX inhibitors

NASA Astrophysics Data System (ADS)

Yatam, Satayanarayana; Gundla, Rambabu; Jadav, Surender Singh; Pedavenkatagari, Narayana reddy; Chimakurthy, Jithendra; Rani B, Namratha; Kedam, Thyagaraju

2018-05-01

Mercapto benzothiazole linked 1,2,4-oxadiazole derivatives were designed (4a-u) as new anti-inflammatory agents using bioisosteric approach and docking studies. The docking results clearly indicated that the compounds 4a-u shown good docking interaction towards COX-2 enzyme. In silico drug-like properties were also calculated for compounds (4a-u) and exhibited significant H-bond acceptor ratio. All compounds were synthesized and biologically evaluated using in vitro COX-1, COX-2 and 5-LOX assays. Compound 4k and 4q (IC50 = 6.8 μM and IC50 = 5.0 μM) found to be potent, selective COX-2 inhibitors and display better anti-inflammatory activity than standard Ibuprofen. Compound 4l and 4e found to be potent inhibitors against 5-LOX (IC50 = 5.1 μM and IC50 = 5.5 μM). The in vivo anti-inflammatory activity studies shown that the compounds 4q and 4k effectively reducing the paw edema volume at 3h and 5h than standard drug Ibuprofen. The DPPH radical scavenging activity provided anti-oxidant activity of compound 4e (IC50 = 25.6 μM) than reference standard Ascorbic acid.

2005 Science and Technology for Chem-Bio Information Systems (S and T CBIS) volume 3 Thursday

DTIC Science & Technology

2005-10-28

radar, lidar, or sodar with computer on-board. Temperature and moisture MW radiometer with computer on- board. Portable meteorological sensors ... Wireless on the go is a way of life now – my cell phone , my PDA, my IPOD (look, I’m “Podcasting”!) and dock it when I’m at home – Same components...Team.. Other specifications will follow… Standardization of the interfaces across all CBRN sensors / devices ! JPEO-CBD 20 Joint Program Executive Office

Comparing Evolutionary Programs and Evolutionary Pattern Search Algorithms: A Drug Docking Application

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hart, W.E.

1999-02-10

Evolutionary programs (EPs) and evolutionary pattern search algorithms (EPSAS) are two general classes of evolutionary methods for optimizing on continuous domains. The relative performance of these methods has been evaluated on standard global optimization test functions, and these results suggest that EPSAs more robustly converge to near-optimal solutions than EPs. In this paper we evaluate the relative performance of EPSAs and EPs on a real-world application: flexible ligand binding in the Autodock docking software. We compare the performance of these methods on a suite of docking test problems. Our results confirm that EPSAs and EPs have comparable performance, and theymore » suggest that EPSAs may be more robust on larger, more complex problems.« less

Electrostatics in protein–protein docking

PubMed Central

Heifetz, Alexander; Katchalski-Katzir, Ephraim; Eisenstein, Miriam

2002-01-01

A novel geometric-electrostatic docking algorithm is presented, which tests and quantifies the electrostatic complementarity of the molecular surfaces together with the shape complementarity. We represent each molecule to be docked as a grid of complex numbers, storing information regarding the shape of the molecule in the real part and information regarding the electrostatic character of the molecule in the imaginary part. The electrostatic descriptors are derived from the electrostatic potential of the molecule. Thus, the electrostatic character of the molecule is represented as patches of positive, neutral, or negative values. The potential for each molecule is calculated only once and stored as potential spheres adequate for exhaustive rotation/translation scans. The geometric-electrostatic docking algorithm is applied to 17 systems, starting form the structures of the unbound molecules. The results—in terms of the complementarity scores of the nearly correct solutions, their ranking in the lists of sorted solutions, and their statistical uniqueness—are compared with those of geometric docking, showing that the inclusion of electrostatic complementarity in docking is very important, in particular in docking of unbound structures. Based on our results, we formulate several "good electrostatic docking rules": The geometric-electrostatic docking procedure is more successful than geometric docking when the potential patches are large and when the potential extends away from the molecular surface and protrudes into the solvent. In contrast, geometric docking is recommended when the electrostatic potential around the molecules to be docked appears homogenous, that is, with a similar sign all around the molecule. PMID:11847280

Extending RosettaDock with water, sugar, and pH for prediction of complex structures and affinities for CAPRI rounds 20-27.

PubMed

Kilambi, Krishna Praneeth; Pacella, Michael S; Xu, Jianqing; Labonte, Jason W; Porter, Justin R; Muthu, Pravin; Drew, Kevin; Kuroda, Daisuke; Schueler-Furman, Ora; Bonneau, Richard; Gray, Jeffrey J

2013-12-01

Rounds 20-27 of the Critical Assessment of PRotein Interactions (CAPRI) provided a testing platform for computational methods designed to address a wide range of challenges. The diverse targets drove the creation of and new combinations of computational tools. In this study, RosettaDock and other novel Rosetta protocols were used to successfully predict four of the 10 blind targets. For example, for DNase domain of Colicin E2-Im2 immunity protein, RosettaDock and RosettaLigand were used to predict the positions of water molecules at the interface, recovering 46% of the native water-mediated contacts. For α-repeat Rep4-Rep2 and g-type lysozyme-PliG inhibitor complexes, homology models were built and standard and pH-sensitive docking algorithms were used to generate structures with interface RMSD values of 3.3 Å and 2.0 Å, respectively. A novel flexible sugar-protein docking protocol was also developed and used for structure prediction of the BT4661-heparin-like saccharide complex, recovering 71% of the native contacts. Challenges remain in the generation of accurate homology models for protein mutants and sampling during global docking. On proteins designed to bind influenza hemagglutinin, only about half of the mutations were identified that affect binding (T55: 54%; T56: 48%). The prediction of the structure of the xylanase complex involving homology modeling and multidomain docking pushed the limits of global conformational sampling and did not result in any successful prediction. The diversity of problems at hand requires computational algorithms to be versatile; the recent additions to the Rosetta suite expand the capabilities to encompass more biologically realistic docking problems. Copyright © 2013 Wiley Periodicals, Inc.

Carbon Dioxide Removal Troubleshooting aboard the International Space Station (ISS) during Space Shuttle (STS) Docked Operations

NASA Technical Reports Server (NTRS)

Matty, Christopher M.; Cover, John M.

2009-01-01

The International Space Station (ISS) represents a largely closed-system habitable volume which requires active control of atmospheric constituents, including removal of exhaled Carbon Dioxide (CO2). The ISS provides a unique opportunity to observe system requirements for (CO2) removal. CO2 removal is managed by the Carbon Dioxide Removal Assembly (CDRA) aboard the US segment of ISS and by Lithium Hydroxide (LiOH) aboard the Space Shuttle (STS). While the ISS and STS are docked, various methods are used to balance the CO2 levels between the two vehicles, including mechanical air handling and management of general crew locations. Over the course of ISS operation, several unexpected anomalies have occurred which have required troubleshooting, including possible compromised performance of the CDRA and LiOH systems, and possible imbalance in CO2 levels between the ISS and STS while docked. This paper will cover efforts to troubleshoot the CO2 removal systems aboard the ISS and docked STS.

Kaleri works with the TORU teleoperated control system in the SM during Expedition 8

NASA Image and Video Library

2004-01-30

ISS008-E-14073 (30 January 2004) --- Cosmonaut Alexander Y. Kaleri, Expedition 8 flight engineer, practices docking procedures with the manual TORU rendezvous system in the Zvezda Service Module on the International Space Station (ISS) in preparation for the docking of the Progress 13 on January 31. With the manual TORU mode, Kaleri can perform necessary guidance functions from Zvezda via two hand controllers in the event of a failure of the “Kurs” automated rendezvous and docking (AR&D) of the Progress. Kaleri represents Rosaviakosmos.

Kaleri works with the TORU teleoperated control system in the SM during Expedition 8

NASA Image and Video Library

2004-01-30

ISS008-E-14076 (30 January 2004) --- Cosmonaut Alexander Y. Kaleri, Expedition 8 flight engineer, practices docking procedures with the manual TORU rendezvous system in the Zvezda Service Module on the International Space Station (ISS) in preparation for the docking of the Progress 13 on January 31. With the manual TORU mode, Kaleri can perform necessary guidance functions from Zvezda via two hand controllers in the event of a failure of the “Kurs” automated rendezvous and docking (AR&D) of the Progress. Kaleri represents Rosaviakosmos.

Kaleri works with the TORU teleoperated control system in the SM during Expedition 8

NASA Image and Video Library

2004-01-30

ISS008-E-14067 (30 January 2004) --- Cosmonaut Alexander Y. Kaleri, Expedition 8 flight engineer, practices docking procedures with the manual TORU rendezvous system in the Zvezda Service Module on the International Space Station (ISS) in preparation for the docking of the Progress 13 on January 31. With the manual TORU mode, Kaleri can perform necessary guidance functions from Zvezda via two hand controllers in the event of a failure of the “Kurs” automated rendezvous and docking (AR&D) of the Progress. Kaleri represents Rosaviakosmos.

AutoDockFR: Advances in Protein-Ligand Docking with Explicitly Specified Binding Site Flexibility

PubMed Central

Ravindranath, Pradeep Anand; Forli, Stefano; Goodsell, David S.; Olson, Arthur J.; Sanner, Michel F.

2015-01-01

Automated docking of drug-like molecules into receptors is an essential tool in structure-based drug design. While modeling receptor flexibility is important for correctly predicting ligand binding, it still remains challenging. This work focuses on an approach in which receptor flexibility is modeled by explicitly specifying a set of receptor side-chains a-priori. The challenges of this approach include the: 1) exponential growth of the search space, demanding more efficient search methods; and 2) increased number of false positives, calling for scoring functions tailored for flexible receptor docking. We present AutoDockFR–AutoDock for Flexible Receptors (ADFR), a new docking engine based on the AutoDock4 scoring function, which addresses the aforementioned challenges with a new Genetic Algorithm (GA) and customized scoring function. We validate ADFR using the Astex Diverse Set, demonstrating an increase in efficiency and reliability of its GA over the one implemented in AutoDock4. We demonstrate greatly increased success rates when cross-docking ligands into apo receptors that require side-chain conformational changes for ligand binding. These cross-docking experiments are based on two datasets: 1) SEQ17 –a receptor diversity set containing 17 pairs of apo-holo structures; and 2) CDK2 –a ligand diversity set composed of one CDK2 apo structure and 52 known bound inhibitors. We show that, when cross-docking ligands into the apo conformation of the receptors with up to 14 flexible side-chains, ADFR reports more correctly cross-docked ligands than AutoDock Vina on both datasets with solutions found for 70.6% vs. 35.3% systems on SEQ17, and 76.9% vs. 61.5% on CDK2. ADFR also outperforms AutoDock Vina in number of top ranking solutions on both datasets. Furthermore, we show that correctly docked CDK2 complexes re-create on average 79.8% of all pairwise atomic interactions between the ligand and moving receptor atoms in the holo complexes. Finally, we show that down-weighting the receptor internal energy improves the ranking of correctly docked poses and that runtime for AutoDockFR scales linearly when side-chain flexibility is added. PMID:26629955

Mathematical model for the simulation of Dynamic Docking Test System (DDST) active table motion

NASA Technical Reports Server (NTRS)

Gates, R. M.; Graves, D. L.

1974-01-01

The mathematical model developed to describe the three-dimensional motion of the dynamic docking test system active table is described. The active table is modeled as a rigid body supported by six flexible hydraulic actuators which produce the commanded table motions.

Pressure Decay Testing Methodology for Quantifying Leak Rates of Full-Scale Docking System Seals

NASA Technical Reports Server (NTRS)

Dunlap, Patrick H., Jr.; Daniels, Christopher C.; Wasowski, Janice L.; Garafolo, Nicholas G.; Penney, Nicholas; Steinetz, Bruce M.

2010-01-01

NASA is developing a new docking system to support future space exploration missions to low-Earth orbit and the Moon. This system, called the Low Impact Docking System, is a mechanism designed to connect the Orion Crew Exploration Vehicle to the International Space Station, the lunar lander (Altair), and other future Constellation Project vehicles. NASA Glenn Research Center is playing a key role in developing the main interface seal for this docking system. This seal will be relatively large with an outside diameter in the range of 54 to 58 in. (137 to 147 cm). As part of this effort, a new test apparatus has been designed, fabricated, and installed to measure leak rates of candidate full-scale seals under simulated thermal, vacuum, and engagement conditions. Using this test apparatus, a pressure decay testing and data processing methodology has been developed to quantify full-scale seal leak rates. Tests performed on untreated 54 in. diameter seals at room temperature in a fully compressed state resulted in leak rates lower than the requirement of less than 0.0025 lbm, air per day (0.0011 kg/day).

Russian Docking Module is lowered

NASA Technical Reports Server (NTRS)

1995-01-01

The Russian-built Docking Module (DM) is lowered for installation into the payload bay of the Space Shuttle Orbiter Atlantis while the spaceplane is in Orbiter Processing Facility bay 2. The module will fly as a primary payload on the second Space Shuttle/Mir space station docking mission, STS-74, which is now scheduled for liftoff in the fall of 1995. During the mission, the module will first be attached with the orbiter's robot arm to the Orbiter Docking System (ODS) in the payload bay of the orbiter Atlantis and then be docked with the Mir. When Atlantis undocks from the Mir, it will leave the new docking module permanently attached to the space station for use during future Shuttle Mir docking missions. The new module will simplify future Shuttle linkups with Mir by improving orbiter clearances when it serves as a bridge between the two space vehicles. The white structures attached to the module's sides are solar panels that will be attached to the Mir after the conclusion of the STS-74 mission.

Robotic hip arthroscopy in human anatomy.

PubMed

Kather, Jens; Hagen, Monika E; Morel, Philippe; Fasel, Jean; Markar, Sheraz; Schueler, Michael

2010-09-01

Robotic technology offers technical advantages that might offer new solutions for hip arthroscopy. Two hip arthroscopies were performed in human cadavers using the da Vinci surgical system. During both surgeries, a robotic camera and 5 or 8 mm da Vinci trocars with instruments were inserted into the hip joint for manipulation. Introduction of cameras and working instruments, docking of the robotic system and instrument manipulation was successful in both cases. The long articulating area of 5 mm instruments limited movements inside the joint; an 8 mm instrument with a shorter area of articulation offered an improved range of motion. Hip arthroscopy using the da Vinci standard system appears a feasible alternative to standard arthroscopy. Instruments and method of application must be modified and improved before routine clinical application but further research in this area seems justified, considering the clinical value of such an approach. Copyright 2010 John Wiley & Sons, Ltd.

Full-Scale System for Quantifying Leakage of Docking System Seals for Space Applications

NASA Technical Reports Server (NTRS)

Dunlap, Patrick H., Jr.; Daniels, Christopher C.; Steinetz, Bruce M.; Erker, Arthur H.; Robbie, Malcolm G.; Wasowski, Janice L.; Drlik, Gary J.; Tong, Michael T.; Penney, Nicholas

2007-01-01

NASA is developing a new docking and berthing system to support future space exploration missions to low-Earth orbit, the Moon, and Mars. This mechanism, called the Low Impact Docking System, is designed to connect pressurized space vehicles and structures. NASA Glenn Research Center is playing a key role in developing advanced technology for the main interface seal for this new docking system. The baseline system is designed to have a fully androgynous mating interface, thereby requiring a seal-on-seal configuration when two systems mate. These seals will be approximately 147 cm (58 in.) in diameter. NASA Glenn has designed and fabricated a new test fixture which will be used to evaluate the leakage of candidate full-scale seals under simulated thermal, vacuum, and engagement conditions. This includes testing under seal-on-seal or seal-on-plate configurations, temperatures from -50 to 50 C (-58 to 122 F), operational and pre-flight checkout pressure gradients, and vehicle misalignment (plus or minus 0.381 cm (0.150 in.)) and gapping (up to 0.10 cm (0.040 in.)) conditions. This paper describes the main design features of the test rig and techniques used to overcome some of the design challenges.

An autonomous rendezvous and docking system using cruise missile technologies

NASA Technical Reports Server (NTRS)

Jones, Ruel Edwin

1991-01-01

In November 1990 the Autonomous Rendezvous & Docking (AR&D) system was first demonstrated for members of NASA's Strategic Avionics Technology Working Group. This simulation utilized prototype hardware from the Cruise Missile and Advanced Centaur Avionics systems. The object was to show that all the accuracy, reliability and operational requirements established for a space craft to dock with Space Station Freedom could be met by the proposed system. The rapid prototyping capabilities of the Advanced Avionics Systems Development Laboratory were used to evaluate the proposed system in a real time, hardware in the loop simulation of the rendezvous and docking reference mission. The simulation permits manual, supervised automatic and fully autonomous operations to be evaluated. It is also being upgraded to be able to test an Autonomous Approach and Landing (AA&L) system. The AA&L and AR&D systems are very similar. Both use inertial guidance and control systems supplemented by GPS. Both use an Image Processing System (IPS), for target recognition and tracking. The IPS includes a general purpose multiprocessor computer and a selected suite of sensors that will provide the required relative position and orientation data. Graphic displays can also be generated by the computer, providing the astronaut / operator with real-time guidance and navigation data with enhanced video or sensor imagery.

Dynamic Docking Test System (DDTS) active table frequency response test results. [Apollo Soyuz Test Project

NASA Technical Reports Server (NTRS)

Gates, R. M.

1974-01-01

Results are presented of the frequency response test performed on the dynamic docking test system (DDTS) active table. Sinusoidal displacement commands were applied to the table and the dynamic response determined from measured actuator responses and accelerometers mounted to the table and one actuator.

ARCADE small-scale docking mechanism for micro-satellites

NASA Astrophysics Data System (ADS)

Boesso, A.; Francesconi, A.

2013-05-01

The development of on-orbit autonomous rendezvous and docking (ARD) capabilities represents a key point for a number of appealing mission scenarios that include activities of on-orbit servicing, automated assembly of modular structures and active debris removal. As of today, especially in the field of micro-satellites ARD, many fundamental technologies are still missing or require further developments and micro-gravity testing. In this framework, the University of Padova, Centre of Studies and Activities for Space (CISAS), developed the Autonomous Rendezvous Control and Docking Experiment (ARCADE), a technology demonstrator intended to fly aboard a BEXUS stratospheric balloon. The goal was to design, build and test, in critical environment conditions, a proximity relative navigation system, a custom-made reaction wheel and a small-size docking mechanism. The ARCADE docking mechanism was designed against a comprehensive set of requirements and it can be classified as small-scale, central, gender mating and unpressurized. The large use of commercial components makes it low-cost and simple to be manufactured. Last, it features a good tolerance to off-nominal docking conditions and a by-design soft docking capability. The final design was extensively verified to be compliant with its requirements by means of numerical simulations and physical testing. In detail, the dynamic behaviour of the mechanism in both nominal and off-nominal conditions was assessed with the multibody dynamics analysis software MD ADAMS 2010 and functional tests were carried out within the fully integrated ARCADE experiment to ensure the docking system efficacy and to highlight possible issues. The most relevant results of the study will be presented and discussed in conclusion to this paper.

Collision avoidance sensor skin

NASA Technical Reports Server (NTRS)

1991-01-01

The objective was to totally eliminate the possibility of a robot (or any mechanism for that matter) inducing a collision in space operations. We were particularly concerned that human beings were safe under all circumstances. This was apparently accomplished, and it is shown that GSFC has a system that is ready for space qualification and flight. However, it soon became apparent that much more could be accomplished with this technology. Payloads could be made invulnerable to collision avoidance and the blind spots behind them eliminated. This could be accomplished by a simple, non-imaging set of 'Capaciflector' sensors on each payload. It also is evident that this system could be used to align and dock the system with a wide margin of safety. Throughout, lighting problems could be ignored, and unexpected events and modeling errors taken in stride. At the same time, computational requirements would be reduced. This can be done in a simple, rugged, reliable manner that will not disturb the form factor of space systems. It will be practical for space applications. The lab experiments indicate we are well on the way to accomplishing this. Still, the research trail goes deeper. It now appears that the sensors can be extended to end effectors to provide precontact information and make robot docking (or any docking connection) very smooth, with minimal loads impacted back into the mating structures. This type of ability would be a major step forward in basic control techniques in space. There are, however, baseline and restructuring issues to be tackled. The payloads must get power and signals to them from the robot or from the astronaut servicing tool. This requires a standard electromechanical interface. Any of several could be used. The GSFC prototype shown in this presentation is a good one. Sensors with their attendant electronics must be added to the payloads, end effectors, and robot arms and integrated into the system.

Orion Handling Qualities During ISS Rendezvous and Docking

NASA Technical Reports Server (NTRS)

Hart, Jeremy J.; Stephens, J. P.; Spehar, P.; Bilimoria, K.; Foster, C.; Gonzalex, R.; Sullivan, K.; Jackson, B.; Brazzel, J.; Hart, J.

2011-01-01

The Orion spacecraft was designed to rendezvous with multiple vehicles in low earth orbit (LEO) and beyond. To perform the required rendezvous and docking task, Orion must provide enough control authority to perform coarse translational maneuvers while maintaining precision to perform the delicate docking corrections. While Orion has autonomous docking capabilities, it is expected that final approach and docking operations with the International Space Station (ISS) will initially be performed in a manual mode. A series of evaluations was conducted by NASA and Lockheed Martin at the Johnson Space Center to determine the handling qualities (HQ) of the Orion spacecraft during different docking and rendezvous conditions using the Cooper-Harper scale. This paper will address the specifics of the handling qualities methodology, vehicle configuration, scenarios flown, data collection tools, and subject ratings and comments. The initial Orion HQ assessment examined Orion docking to the ISS. This scenario demonstrates the Translational Hand Controller (THC) handling qualities of Orion. During this initial assessment, two different scenarios were evaluated. The first was a nominal docking approach to a stable ISS, with Orion initializing with relative position dispersions and a closing rate of approximately 0.1 ft/sec. The second docking scenario was identical to the first, except the attitude motion of the ISS was modeled to simulate a stress case ( 1 degree deadband per axis and 0.01 deg/sec rate deadband per axis). For both scenarios, subjects started each run on final approach at a docking port-to-port range of 20 ft. Subjects used the THC in pulse mode with cues from the docking camera image, window views, and range and range rate data displayed on the Orion display units. As in the actual design, the attitude of the Orion vehicle was held by the automated flight control system at 0.5 degree deadband per axis. Several error sources were modeled including Reaction Control System (RCS) jet angular and position misalignment, RCS thrust magnitude uncertainty, RCS jet force direction uncertainty due to self plume impingement, and Orion center of mass uncertainty.

Russian RSC Energia employees inspect DM in SSPF

NASA Technical Reports Server (NTRS)

1995-01-01

Employees of the Russian aerospace company RSC Energia prepare to conduct final inspections of the Russian-built Docking Module in the Space Station Processing Facility at KSC. The module will fly as a primary payload on the second Space Shuttle/Mir space station docking mission, STS-74, which is now scheduled for liftoff in the fall of 1995. During the mission, the module will first be attached with the orbiter's robot arm to the Orbiter Docking System (ODS) in the payload bay of the orbiter Atlantis and then be docked with the Mir. When Atlantis undocks from the Mir, it will leave the new docking module permanently attached to the space station for use during future Shuttle Mir docking missions. The new module will simplify future Shuttle linkups with Mir by improving orbiter clearances when it serves as a bridge between the two space vehicles.

Russian RSC Energia employees attach trunnions to DM

NASA Technical Reports Server (NTRS)

1995-01-01

Employees of the Russian aerospace company RSC Energia attach trunnions to the Russian-built docking module in the Space Station Processing Facility at KSC so that it can be mounted in the payload bay of the Space Shuttle orbiter Atlantis. The module will fly as a primary payload on the second Space Shuttle/Mir space station docking mission, STS-74, which is now scheduled for liftoff in the fall of 1995. During the mission, the module will first be attached with the orbiter's robot arm to the Orbiter Docking System (ODS) in the payload bay of the orbiter Atlantis and then be docked with the Mir. When Atlantis undocks from the Mir, it will leave the new docking module permanently attached to the space station for use during future Shuttle Mir docking missions. The new module will simplify future Shuttle linkups with Mir by improving orbiter clearances when it serves as a bridge between the two space vehicles.

Space Operations Center, Shuttle Interaction Study. Volume 2: Appendices, Book 1 of 2

NASA Technical Reports Server (NTRS)

1981-01-01

The feasibility of shuttle orbiter docking to the Space Operations Center (SOC) is studied. The in-orbit relative motion of the free flying orbiter and SOC was simulated, accounting for the Orbiter RCS and digital autopilot (DAP) systems, orbital mechanics, center of gravity offset of the orbiter docking port, aero and gravity gradient effects, and other pertinent natural and man-made phenomena. Since there is no specified flight path and procedure for docking, terminal closure sensitivities were investigated. Orbiter approach direction, Orbiter approach attitude out of plane, DAP thruster compensation mode, final ballistic docking distance and time to dock, rate and excursion attitude deadbands, and selection of various thruster combinations (differing from nominal) for translational pulses are considered.

Diastereoselective synthesis and molecular docking studies of novel fused tetrahydropyridine derivatives as new inhibitors of HIV protease

NASA Astrophysics Data System (ADS)

Mohammadi, Ali A.; Taheri, Salman; Amouzegar, Ali; Ahdenov, Reza; Halvagar, Mohammad Reza; Sadr, Ahmad Shahir

2017-07-01

An efficient one-pot, catalyst-free, and four-components procedure for the synthesis of novel 10b-hydroxy-4-nitro-5-phenyl-2,3,5,5a-tetrahydro-1H-imidazo[1,2-a]indeno[2,1-e]pyridin-6(10bH)-one derivatives from corresponding diamine, nitro ketene dithioacetal, aldehydes and 1,3-indandione in ethanol has been achieved upon a Knoevenagel condensation-Michael addition-tautomerism-cyclisation sequence. All the newly synthesized compounds were screened for molecular docking studies. Molecular docking studies were carried out using the crystal structure of HIV protease enzyme. Some of the compounds obtain minimum binding energy and good affinity toward the active pocket of HIV protease enzyme in compare with Saquinavir as a standard HIV protease inhibitor.

A Drosophila protein-tyrosine phosphatase associates with an adapter protein required for axonal guidance.

PubMed

Clemens, J C; Ursuliak, Z; Clemens, K K; Price, J V; Dixon, J E

1996-07-19

We have used the yeast two-hybrid system to isolate a novel Drosophila adapter protein, which interacts with the Drosophila protein-tyrosine phosphatase (PTP) dPTP61F. Absence of this protein in Drosophila causes the mutant photoreceptor axon phenotype dreadlocks (dock) (Garrity, P. A., Rao, Y., Salecker, I., and Zipursky, S. L.(1996) Cell 85, 639-650). Dock is similar to the mammalian oncoprotein Nck and contains three Src homology 3 (SH3) domains and one Src homology 2 (SH2) domain. The interaction of dPTP61F with Dock was confirmed in vivo by immune precipitation experiments. A sequence containing five PXXP motifs from the non-catalytic domain of the PTP is sufficient for interaction with Dock. This suggests that binding to the PTP is mediated by one or more of the SH3 domains of Dock. Immune precipitations of Dock also co-precipitate two tyrosine-phosphorylated proteins having molecular masses of 190 and 145 kDa. Interactions between Dock and these tyrosine-phosphorylated proteins are likely mediated by the Dock SH2 domain. These findings identify potential signal-transducing partners of Dock and propose a role for dPTP61F and the unidentified phosphoproteins in axonal guidance.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kring, C.T.; Varma, V.K.; Jatko, W.B.

The US Army and Team Crusader (United Defense, Lockheed Martin Armament Systems, etc.) are developing the next generation howitzer, the Crusader. The development program includes an advanced, self-propelled liquid propellant howitzer and a companion resupply vehicle. The resupply vehicle is intended to rendezvous with the howitzer near the battlefront and replenish ammunition, fuel, and other material. The Army has recommended that Crusader incorporate new and innovative technologies to improve performance and safety. One conceptual design proposes a robotic resupply boom on the resupply vehicle to upload supplies to the howitzer. The resupply boom would normally be retracted inside the resupplymore » vehicle during transit. When the two vehicles are within range of the resupply boom, the boom would be extended to a receiving port on the howitzer. In order to reduce exposure to small arms fire or nuclear, biological, and chemical hazards, the crew would remain inside the resupply vehicle during the resupply operation. The process of extending the boom and linking with the receiving port is called docking. A boom operator would be designated to maneuver the boom into contact with the receiving port using a mechanical joystick. The docking operation depends greatly upon the skill of the boom operator to manipulate the boom into docking position. Computer simulations at the National Aeronautics and Space Administration have shown that computer-assisted or autonomous docking can improve the ability of the operator to dock safely and quickly. This document describes the present status of the Crusader Autonomous Docking System (CADS) implemented at Oak Ridge National laboratory (ORNL). The purpose of the CADS project is to determine the feasibility and performance limitations of vision systems to satisfy the autonomous docking requirements for Crusader and conduct a demonstration under controlled conditions.« less

Global Positioning System Synchronized Active Light Autonomous Docking System

NASA Technical Reports Server (NTRS)

Howard, Richard T. (Inventor); Book, Michael L. (Inventor); Bryan, Thomas C. (Inventor); Bell, Joseph L. (Inventor)

1996-01-01

A Global Positioning System Synchronized Active Light Autonomous Docking System (GPSSALADS) for automatically docking a chase vehicle with a target vehicle comprising at least one active light emitting target which is operatively attached to the target vehicle. The target includes a three-dimensional array of concomitantly flashing lights which flash at a controlled common frequency. The GPSSALADS further comprises a visual tracking sensor operatively attached to the chase vehicle for detecting and tracking the target vehicle. Its performance is synchronized with the flash frequency of the lights by a synchronization means which is comprised of first and second internal clocks operatively connected to the active light target and visual tracking sensor, respectively, for providing timing control signals thereto, respectively. The synchronization means further includes first and second Global Positioning System receivers operatively connected to the first and second internal clocks, respectively, for repeatedly providing simultaneous synchronization pulses to the internal clocks, respectively. In addition, the GPSSALADS includes a docking process controller means which is operatively attached to the chase vehicle and is responsive to the visual tracking sensor for producing commands for the guidance and propulsion system of the chase vehicle.

Global Positioning System Synchronized Active Light Autonomous Docking System

NASA Technical Reports Server (NTRS)

Howard, Richard (Inventor)

1994-01-01

A Global Positioning System Synchronized Active Light Autonomous Docking System (GPSSALADS) for automatically docking a chase vehicle with a target vehicle comprises at least one active light emitting target which is operatively attached to the target vehicle. The target includes a three-dimensional array of concomitantly flashing lights which flash at a controlled common frequency. The GPSSALADS further comprises a visual tracking sensor operatively attached to the chase vehicle for detecting and tracking the target vehicle. Its performance is synchronized with the flash frequency of the lights by a synchronization means which is comprised of first and second internal clocks operatively connected to the active light target and visual tracking sensor, respectively, for providing timing control signals thereto, respectively. The synchronization means further includes first and second Global Positioning System receivers operatively connected to the first and second internal clocks, respectively, for repeatedly providing simultaneous synchronization pulses to the internal clocks, respectively. In addition, the GPSSALADS includes a docking process controller means which is operatively attached to the chase vehicle and is responsive to the visual tracking sensor for producing commands for the guidance and propulsion system of the chase vehicle.

Telerobotic rendezvous and docking vision system architecture

NASA Technical Reports Server (NTRS)

Gravely, Ben; Myers, Donald; Moody, David

1992-01-01

This research program has successfully demonstrated a new target label architecture that allows a microcomputer to determine the position, orientation, and identity of an object. It contains a CAD-like database with specific geometric information about the object for approach, grasping, and docking maneuvers. Successful demonstrations were performed selecting and docking an ORU box with either of two ORU receptacles. Small, but significant differences were seen in the two camera types used in the program, and camera sensitive program elements have been identified. The software has been formatted into a new co-autonomy system which provides various levels of operator interaction and promises to allow effective application of telerobotic systems while code improvements are continuing.

Theoretical Study of Free Energy in Docking Stability of Azurin(II)-Cytochrome c551(II) Complex System

NASA Astrophysics Data System (ADS)

Yamamoto, Tetsunori; Nishikawa, Keigo; Sugiyama, Ayumu; Purqon, Acep; Mizukami, Taku; Shimahara, Hideto; Nagao, Hidemi; Nishikawa, Kiyoshi

2008-02-01

The docking structure of the Azurin-Cytochrome C551 is presented. We investigate a complex system of Azurin(II)-Cytochrome C551(II) by using molecular dynamics simulation. We estimate some physical properties, such as root-mean-square deviation (RMSD), binding energy between Azurin and Cytochrome C551, distance between Azurin(II) and Cytochrome C551(II) through center of mass and each active site. We also discuss docking stability in relation to the configuration by free energy between Azurin(II)-Cytochrome C551(II) and Azurin(I)-Cytochrome C551(III).

Synthesis, characterization, antimicrobial screening and in silico studies of Schiff bases derived from trans-para-methoxycinnamaldehyde

NASA Astrophysics Data System (ADS)

Obasi, N. L.; Kaior, G. U.; Ibezim, A.; Ochonogor, Alfred E.; Rhyman, Lydia; Uahengo, Veikko; Lutter, Michael; Jurkschat, Klaus; Ramasami, Ponnadurai

2017-12-01

Two Schiff bases namely N,N‧-Bis-[3-(4-metoxy-phenyl)-allylidene]ethane-1,2-diamine (TPMC/EDA) and [3-(4-methoxy-phenyl)-allylidene]-phenyl-amine (TPMC/AN) were synthesized. They were characterized using elemental microanalysis, IR, NMR, UV and mass spectroscopies. Single crystals of TPMC/AN were also analyzed by X-ray diffraction and the compound was examined using B3LYP/6-311++G(d,p) method. A Monoclinic crystal system and space groups of P21/c were obtained for the crystal. Docking calculations on the compounds showed they interacted with fungal N-myristoyltransferase and bacteria DNA gyrase at 2.62-2.95 and 190.26-98.99 μM ranges. The predicted docked poses identified unique binding modes of the compounds and vital intermolecular interactions. The anti-microbial screening of the compounds were carried out against Escherichia coli, Bacillus subtillis, Staphylococcus aureus, Pseudomonas aeruginosa, Candida albicans and Aspergillus niger using agar well diffusion method. The standard drugs used were the anti-bacterial ciprofloxacin and the anti-fungal fluconazole. The compounds showed activity against all the microorganisms comparable to the used standard drugs. TPMC/EDA was more active than the standard fungal drug in the screening against the fungi strain, Aspergillus niger. It showed the MIC and IZD of 1.3 mg/ml and 9.0 mm respectively. These suggest that the compounds are potential bactericidal and fungicidal candidates.

High performance transcription factor-DNA docking with GPU computing

PubMed Central

2012-01-01

Background Protein-DNA docking is a very challenging problem in structural bioinformatics and has important implications in a number of applications, such as structure-based prediction of transcription factor binding sites and rational drug design. Protein-DNA docking is very computational demanding due to the high cost of energy calculation and the statistical nature of conformational sampling algorithms. More importantly, experiments show that the docking quality depends on the coverage of the conformational sampling space. It is therefore desirable to accelerate the computation of the docking algorithm, not only to reduce computing time, but also to improve docking quality. Methods In an attempt to accelerate the sampling process and to improve the docking performance, we developed a graphics processing unit (GPU)-based protein-DNA docking algorithm. The algorithm employs a potential-based energy function to describe the binding affinity of a protein-DNA pair, and integrates Monte-Carlo simulation and a simulated annealing method to search through the conformational space. Algorithmic techniques were developed to improve the computation efficiency and scalability on GPU-based high performance computing systems. Results The effectiveness of our approach is tested on a non-redundant set of 75 TF-DNA complexes and a newly developed TF-DNA docking benchmark. We demonstrated that the GPU-based docking algorithm can significantly accelerate the simulation process and thereby improving the chance of finding near-native TF-DNA complex structures. This study also suggests that further improvement in protein-DNA docking research would require efforts from two integral aspects: improvement in computation efficiency and energy function design. Conclusions We present a high performance computing approach for improving the prediction accuracy of protein-DNA docking. The GPU-based docking algorithm accelerates the search of the conformational space and thus increases the chance of finding more near-native structures. To the best of our knowledge, this is the first ad hoc effort of applying GPU or GPU clusters to the protein-DNA docking problem. PMID:22759575

STS-71 hardware assembly view

NASA Image and Video Library

1994-12-02

S94-47810 (2 Dec. 1994) --- Lockheed Space Operations Company workers in the Extended Duration Orbiter (EDO) Facility, located inside the Vehicle Assembly Building (VAB), carefully hoist the Orbiter Docking System (ODS) from its shipping container into a test stand. The ODS was shipped in a horizontal position to the Kennedy Space Center (KSC) from contractor Rockwell Aerospace's Downey plant. Once the ODS is upright, work can continue to prepare the hardware for the first docking of the United States Space Shuttle and Russian Space Station MIR in 1995. The ODS contains both United States-made and Russian-made hardware. The black band is Russian-made thermal insulation protecting part of the docking mechanism, also Russian-made, called the Androgynous Peripheral Docking System (APDS). A red protective cap covers the APDS itself. Other elements of the ODS, most of it protected by white United States-made thermal insulation, were developed by Rockwell, which also integrated and checked out the assembled Russian-United States system.

Review of Full-Scale Docking Seal Testing Capabilities

NASA Technical Reports Server (NTRS)

Dunlap, Patrick H., Jr.; Penney, Nicholas; Wasowski, Janice L.; Daniels, Christopher C.; Steinetz, Bruce M.

2008-01-01

NASA is developing a new docking system to support future space exploration missions to low-Earth orbit, the Moon, and Mars. This mechanism, called the Low Impact Docking System (LIDS), is designed to connect pressurized space vehicles and structures including the Crew Exploration Vehicle, International Space Station, and lunar lander. NASA Glenn Research Center (GRC) is playing a key role in developing the main interface seal for this new docking system. These seals will be approximately 147 cm (58 in.) in diameter. To evaluate the performance of the seals under simulated operating conditions, NASA GRC is developing two new test rigs: a non-actuated version that will be used to measure seal leak rates and an actuated test rig that will be able to measure both seal leak rates and loads. Both test rigs will be able to evaluate the seals under seal-on-seal or seal-on-plate configurations at temperatures from -50 to 50 C (-58 to 122 F) under operational and pre-flight checkout pressure gradients in both aligned and misaligned conditions.

Performance of Subscale Docking Seals Under Simulated Temperature Conditions

NASA Technical Reports Server (NTRS)

Smith, Ian M.; Daniels, Christopher C.

2008-01-01

A universal docking system is being developed by the National Aeronautics and Space Administration (NASA) to support future space exploration missions to low Earth orbit (LEO), to the moon, and to Mars. The candidate docking seals for the system are a composite design consisting of elastomer seal bulbs molded into the front and rear sides of a metal ring. The test specimens were subscale seals with two different elastomer cross-sections and a 12-in. outside diameter. The seal assemblies were mated in elastomer seal-on-metal plate and elastomer seal-on-elastomer seal configurations. The seals were manufactured from S0383-70 silicone elastomer compound. Nominal and off-nominal joint configurations were examined. Both the compression load required to mate the seals and the leak rate observed were recorded while the assemblies were subjected to representative docking system operating temperatures of -58, 73, and 122 F (-50, 23, and 50 C). Both the loads required to fully compress the seals and their leak rates were directly proportional to the test temperature.

Combining Machine Learning Systems and Multiple Docking Simulation Packages to Improve Docking Prediction Reliability for Network Pharmacology

PubMed Central

Hsin, Kun-Yi; Ghosh, Samik; Kitano, Hiroaki

2013-01-01

Increased availability of bioinformatics resources is creating opportunities for the application of network pharmacology to predict drug effects and toxicity resulting from multi-target interactions. Here we present a high-precision computational prediction approach that combines two elaborately built machine learning systems and multiple molecular docking tools to assess binding potentials of a test compound against proteins involved in a complex molecular network. One of the two machine learning systems is a re-scoring function to evaluate binding modes generated by docking tools. The second is a binding mode selection function to identify the most predictive binding mode. Results from a series of benchmark validations and a case study show that this approach surpasses the prediction reliability of other techniques and that it also identifies either primary or off-targets of kinase inhibitors. Integrating this approach with molecular network maps makes it possible to address drug safety issues by comprehensively investigating network-dependent effects of a drug or drug candidate. PMID:24391846

Berthing simulator for space station and orbiter

NASA Technical Reports Server (NTRS)

Veerasamy, Sam

1991-01-01

The development of a real-time man-in-the-loop berthing simulator is in progress at NASA Lyndon B. Johnson Space Center (JSC) to conduct a parametric study and to measure forces during contact conditions of the actual docking mechanisms for the Space Station Freedom and the orbiter. In berthing, the docking ports of the Space Station and the orbiter are brought together using the orbiter robotic arm to control the relative motion of the vehicles. The berthing simulator consists of a dynamics docking test system (DDTS), computer system, simulator software, and workstations. In the DDTS, the Space Station, and the orbiter docking mechanisms are mounted on a six-degree-of-freedom (6 DOF) table and a fixed platform above the table. Six load cells are used on the fixed platform to measure forces during contact conditions of the docking mechanisms. Two Encore Concept 32/9780 computers are used to simulate the orbiter robotic arm and to operate the berthing simulator. A systematic procedure for a real-time dynamic initialization is being developed to synchronize the Space Station docking port trajectory with the 6 DOF table movement. The berthing test can be conducted manually or automatically and can be extended for any two orbiting vehicles using a simulated robotic arm. The real-time operation of the berthing simulator is briefly described.

Autonomous docking ground demonstration (category 3)

NASA Technical Reports Server (NTRS)

Lamkin, Steve L.; Eick, Richard E.; Baxter, James M.; Boyd, M. G.; Clark, Fred D.; Lee, Thomas Q.; Othon, L. T.; Prather, Joseph L.; Spehar, Peter T.; Teders, Rebecca J.

1991-01-01

The NASA Johnson Space Center (JSC) is involved in the development of an autonomous docking ground demonstration. The demonstration combines the technologies, expertise and facilities of the JSC Tracking and Communications Division (EE), Structures and Mechanics Division (ES), and the Navigation, Guidance and Control Division (EG) and their supporting contractors. The autonomous docking ground demonstration is an evaluation of the capabilities of the laser sensor system to support the docking phase (12ft to contact) when operated in conjunction with the Guidance, Navigation and Control Software. The docking mechanism being used was developed for the Apollo Soyuz Test Program. This demonstration will be conducted using the Six-Degrees of Freedom (6-DOF) Dynamic Test System (DTS). The DTS environment simulates the Space Station Freedom as the stationary or target vehicle and the Orbiter as the active or chase vehicle. For this demonstration the laser sensor will be mounted on the target vehicle and the retroreflectors on the chase vehicle. This arrangement was used to prevent potential damage to the laser. The sensor system. GN&C and 6-DOF DTS will be operated closed-loop. Initial condition to simulate vehicle misalignments, translational and rotational, will be introduced within the constraints of the systems involved. Detailed description of each of the demonstration components (e.g., Sensor System, GN&C, 6-DOF DTS and supporting computer configuration) including their capabilities and limitations will be discussed. A demonstration architecture drawing and photographs of the test configuration will be presented.

Autonomous docking ground demonstration (category 3)

NASA Astrophysics Data System (ADS)

Lamkin, Steve L.; Eick, Richard E.; Baxter, James M.; Boyd, M. G.; Clark, Fred D.; Lee, Thomas Q.; Othon, L. T.; Prather, Joseph L.; Spehar, Peter T.; Teders, Rebecca J.

The NASA Johnson Space Center (JSC) is involved in the development of an autonomous docking ground demonstration. The demonstration combines the technologies, expertise and facilities of the JSC Tracking and Communications Division (EE), Structures and Mechanics Division (ES), and the Navigation, Guidance and Control Division (EG) and their supporting contractors. The autonomous docking ground demonstration is an evaluation of the capabilities of the laser sensor system to support the docking phase (12ft to contact) when operated in conjunction with the Guidance, Navigation and Control Software. The docking mechanism being used was developed for the Apollo Soyuz Test Program. This demonstration will be conducted using the Six-Degrees of Freedom (6-DOF) Dynamic Test System (DTS). The DTS environment simulates the Space Station Freedom as the stationary or target vehicle and the Orbiter as the active or chase vehicle. For this demonstration the laser sensor will be mounted on the target vehicle and the retroreflectors on the chase vehicle. This arrangement was used to prevent potential damage to the laser. The sensor system. GN&C and 6-DOF DTS will be operated closed-loop. Initial condition to simulate vehicle misalignments, translational and rotational, will be introduced within the constraints of the systems involved. Detailed description of each of the demonstration components (e.g., Sensor System, GN&C, 6-DOF DTS and supporting computer configuration) including their capabilities and limitations will be discussed. A demonstration architecture drawing and photographs of the test configuration will be presented.

Multiple ligand simultaneous docking: orchestrated dancing of ligands in binding sites of protein.

PubMed

Li, Huameng; Li, Chenglong

2010-07-30

Present docking methodologies simulate only one single ligand at a time during docking process. In reality, the molecular recognition process always involves multiple molecular species. Typical protein-ligand interactions are, for example, substrate and cofactor in catalytic cycle; metal ion coordination together with ligand(s); and ligand binding with water molecules. To simulate the real molecular binding processes, we propose a novel multiple ligand simultaneous docking (MLSD) strategy, which can deal with all the above processes, vastly improving docking sampling and binding free energy scoring. The work also compares two search strategies: Lamarckian genetic algorithm and particle swarm optimization, which have respective advantages depending on the specific systems. The methodology proves robust through systematic testing against several diverse model systems: E. coli purine nucleoside phosphorylase (PNP) complex with two substrates, SHP2NSH2 complex with two peptides and Bcl-xL complex with ABT-737 fragments. In all cases, the final correct docking poses and relative binding free energies were obtained. In PNP case, the simulations also capture the binding intermediates and reveal the binding dynamics during the recognition processes, which are consistent with the proposed enzymatic mechanism. In the other two cases, conventional single-ligand docking fails due to energetic and dynamic coupling among ligands, whereas MLSD results in the correct binding modes. These three cases also represent potential applications in the areas of exploring enzymatic mechanism, interpreting noisy X-ray crystallographic maps, and aiding fragment-based drug design, respectively. 2010 Wiley Periodicals, Inc.

Intuitive, but not simple: including explicit water molecules in protein-protein docking simulations improves model quality.

PubMed

Parikh, Hardik I; Kellogg, Glen E

2014-06-01

Characterizing the nature of interaction between proteins that have not been experimentally cocrystallized requires a computational docking approach that can successfully predict the spatial conformation adopted in the complex. In this work, the Hydropathic INTeractions (HINT) force field model was used for scoring docked models in a data set of 30 high-resolution crystallographically characterized "dry" protein-protein complexes and was shown to reliably identify native-like models. However, most current protein-protein docking algorithms fail to explicitly account for water molecules involved in bridging interactions that mediate and stabilize the association of the protein partners, so we used HINT to illuminate the physical and chemical properties of bridging waters and account for their energetic stabilizing contributions. The HINT water Relevance metric identified the "truly" bridging waters at the 30 protein-protein interfaces and we utilized them in "solvated" docking by manually inserting them into the input files for the rigid body ZDOCK program. By accounting for these interfacial waters, a statistically significant improvement of ∼24% in the average hit-count within the top-10 predictions the protein-protein dataset was seen, compared to standard "dry" docking. The results also show scoring improvement, with medium and high accuracy models ranking much better than incorrect ones. These improvements can be attributed to the physical presence of water molecules that alter surface properties and better represent native shape and hydropathic complementarity between interacting partners, with concomitantly more accurate native-like structure predictions. © 2013 Wiley Periodicals, Inc.

Overview of Carbon Dioxide Control Issues During International Space Station/Space Shuttle Joint Docked Operations

NASA Technical Reports Server (NTRS)

Matty, Christopher M.

2010-01-01

Crewed space vehicles have a common requirement to remove the carbon dioxide (CO2) created by the metabolic processes of the crew. The space shuttle [Space Transportation System (STS)] and International Space Station (ISS) each have systems in place that allow control and removal of CO2 from the habitable cabin environment. During periods in which the space shuttle is docked to the ISS, known as "joint docked operations," the space shuttle and ISS share a common atmosphere environment. During this period, an elevated amount of CO2 is produced through the combined metabolic activity of the STS and ISS crews. This elevated CO2 production, together with the large effective atmosphere created by collective volumes of the docked vehicles, creates a unique set of requirements for CO2 removal. This paper will describe individual CO2 control plans implemented by STS and ISS engineering teams, as well as the integrated plans used when both vehicles are docked. The paper will also discuss some of the issues and anomalies experienced by both engineering teams.

Automated Docking Screens: A Feasibility Study

PubMed Central

2009-01-01

Molecular docking is the most practical approach to leverage protein structure for ligand discovery, but the technique retains important liabilities that make it challenging to deploy on a large scale. We have therefore created an expert system, DOCK Blaster, to investigate the feasibility of full automation. The method requires a PDB code, sometimes with a ligand structure, and from that alone can launch a full screen of large libraries. A critical feature is self-assessment, which estimates the anticipated reliability of the automated screening results using pose fidelity and enrichment. Against common benchmarks, DOCK Blaster recapitulates the crystal ligand pose within 2 Å rmsd 50−60% of the time; inferior to an expert, but respectrable. Half the time the ligand also ranked among the top 5% of 100 physically matched decoys chosen on the fly. Further tests were undertaken culminating in a study of 7755 eligible PDB structures. In 1398 cases, the redocked ligand ranked in the top 5% of 100 property-matched decoys while also posing within 2 Å rmsd, suggesting that unsupervised prospective docking is viable. DOCK Blaster is available at http://blaster.docking.org. PMID:19719084

Automated docking screens: a feasibility study.

PubMed

Irwin, John J; Shoichet, Brian K; Mysinger, Michael M; Huang, Niu; Colizzi, Francesco; Wassam, Pascal; Cao, Yiqun

2009-09-24

Molecular docking is the most practical approach to leverage protein structure for ligand discovery, but the technique retains important liabilities that make it challenging to deploy on a large scale. We have therefore created an expert system, DOCK Blaster, to investigate the feasibility of full automation. The method requires a PDB code, sometimes with a ligand structure, and from that alone can launch a full screen of large libraries. A critical feature is self-assessment, which estimates the anticipated reliability of the automated screening results using pose fidelity and enrichment. Against common benchmarks, DOCK Blaster recapitulates the crystal ligand pose within 2 A rmsd 50-60% of the time; inferior to an expert, but respectrable. Half the time the ligand also ranked among the top 5% of 100 physically matched decoys chosen on the fly. Further tests were undertaken culminating in a study of 7755 eligible PDB structures. In 1398 cases, the redocked ligand ranked in the top 5% of 100 property-matched decoys while also posing within 2 A rmsd, suggesting that unsupervised prospective docking is viable. DOCK Blaster is available at http://blaster.docking.org .

Total robotic radical rectal resection with da Vinci Xi system: single docking, single phase technique.

PubMed

Tamhankar, Anup Sunil; Jatal, Sudhir; Saklani, Avanish

2016-12-01

This study aims to assess the advantages of Da Vinci Xi system in rectal cancer surgery. It also assesses the initial oncological outcomes after rectal resection with this system from a tertiary cancer center in India. Robotic rectal surgery has distinct advantages over laparoscopy. Total robotic resection is increasing following the evolution of hybrid technology. The latest Da Vinci Xi system (Intuitive Surgical, Sunnyvale, USA) is enabled with newer features to make total robotic resection possible with single docking and single phase. Thirty-six patients underwent total robotic resection in a single phase and single docking. We used newer port positions in a straight line. Median distance from the anal verge was 4.5 cm. Median robotic docking time and robotic procedure time were 9 and 280 min, respectively. Median blood loss was 100 mL. One patient needed conversion to an open approach due to advanced disease. Circumferential resection margin and longitudinal resection margins were uninvolved in all other patients. Median lymph node yield was 10. Median post-operative stay was 7 days. There were no intra-operative adverse events. The latest Da Vinci Xi system has made total robotic rectal surgery feasible in single docking and single phase. With the new system, four arm total robotic rectal surgery may replace the hybrid technique of laparoscopic and robotic surgery for rectal malignancies. The learning curve for the new system appears to be shorter than anticipated. Early perioperative and oncological outcomes of total robotic rectal surgery with the new system are promising. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

The Next Generation Advanced Video Guidance Sensor: Flight Heritage and Current Development

NASA Technical Reports Server (NTRS)

Howard, Richard T.; Bryan, Thomas C.

2009-01-01

The Next Generation Advanced Video Guidance Sensor (NGAVGS) is the latest in a line of sensors that have flown four times in the last 10 years. The NGAVGS has been under development for the last two years as a long-range proximity operations and docking sensor for use in an Automated Rendezvous and Docking (AR&D) system. The first autonomous rendezvous and docking in the history of the U.S. Space Program was successfully accomplished by Orbital Express, using the Advanced Video Guidance Sensor (AVGS) as the primary docking sensor. That flight proved that the United States now has a mature and flight proven sensor technology for supporting Crew Exploration Vehicles (CEV) and Commercial Orbital Transport Systems (COTS) Automated Rendezvous and Docking (AR&D). NASA video sensors have worked well in the past: the AVGS used on the Demonstration of Autonomous Rendezvous Technology (DART) mission operated successfully in "spot mode" out to 2 km, and the first generation rendezvous and docking sensor, the Video Guidance Sensor (VGS), was developed and successfully flown on Space Shuttle flights in 1997 and 1998. This paper presents the flight heritage and results of the sensor technology, some hardware trades for the current sensor, and discusses the needs of future vehicles that may rendezvous and dock with the International Space Station (ISS) and other Constellation vehicles. It also discusses approaches for upgrading AVGS to address parts obsolescence, and concepts for minimizing the sensor footprint, weight, and power requirements. In addition, the testing of the various NGAVGS development units will be discussed along with the use of the NGAVGS as a proximity operations and docking sensor.

Computational analysis for selectivity of histone deacetylase inhibitor by replica-exchange umbrella sampling molecular dynamics simulations

NASA Astrophysics Data System (ADS)

Tsukamoto, Shuichiro; Sakae, Yoshitake; Itoh, Yukihiro; Suzuki, Takayoshi; Okamoto, Yuko

2018-03-01

We performed protein-ligand docking simulations with a ligand T247, which has been reported as a selective inhibitor of a histone deacetylase HDAC3, by the replica-exchange umbrella sampling method in order to estimate the free energy profiles along ligand docking pathways of HDAC3-T247 and HDAC2-T247 systems. The simulation results showed that the docked state of the HDAC3-T247 system is more stable than that of the HDAC2-T247 system although the amino-acid sequences and structures of HDAC3 and HDAC2 are very similar. By comparing structures obtained from the simulations of both systems, we found the difference between structures of hydrophobic residues at the entrance of the catalytic site. Moreover, we performed conventional molecular dynamics simulations of HDAC3 and HDAC2 systems without T247, and the results also showed the same difference of the hydrophobic structures. Therefore, we consider that this hydrophobic structure contributes to the stabilization of the docked state of the HDAC3-T247 system. Furthermore, we show that Tyr209, which is one of the hydrophobic residues in HDAC2, plays a key role in the instability from the simulation results of a mutated-HDAC2 system.

An autonomous rendezvous and docking system using cruise missile technology

NASA Technical Reports Server (NTRS)

Jones, ED; Nicholson, Bruce

1991-01-01

In November 1990 General Dynamics demonstrated an AR&D system for members of the Strategic Avionics Technology Working Group. This simulation utilized prototype hardware derived from the Cruise Missile and Centaur avionics systems. The object of this proof of concept demonstration was to show that all the accuracy, reliability, and operational requirements established for a spacecraft to dock with Space Station Freedom could be met by the proposed AR&D system.

Autonomous Docking Based on Infrared System for Electric Vehicle Charging in Urban Areas

PubMed Central

Pérez, Joshué; Nashashibi, Fawzi; Lefaudeux, Benjamin; Resende, Paulo; Pollard, Evangeline

2013-01-01

Electric vehicles are progressively introduced in urban areas, because of their ability to reduce air pollution, fuel consumption and noise nuisance. Nowadays, some big cities are launching the first electric car-sharing projects to clear traffic jams and enhance urban mobility, as an alternative to the classic public transportation systems. However, there are still some problems to be solved related to energy storage, electric charging and autonomy. In this paper, we present an autonomous docking system for electric vehicles recharging based on an embarked infrared camera performing infrared beacons detection installed in the infrastructure. A visual servoing system coupled with an automatic controller allows the vehicle to dock accurately to the recharging booth in a street parking area. The results show good behavior of the implemented system, which is currently deployed as a real prototype system in the city of Paris. PMID:23429581

Autonomous docking based on infrared system for electric vehicle charging in urban areas.

PubMed

Pérez, Joshué; Nashashibi, Fawzi; Lefaudeux, Benjamin; Resende, Paulo; Pollard, Evangeline

2013-02-21

Electric vehicles are progressively introduced in urban areas, because of their ability to reduce air pollution, fuel consumption and noise nuisance. Nowadays, some big cities are launching the first electric car-sharing projects to clear traffic jams and enhance urban mobility, as an alternative to the classic public transportation systems. However, there are still some problems to be solved related to energy storage, electric charging and autonomy. In this paper, we present an autonomous docking system for electric vehicles recharging based on an embarked infrared camera performing infrared beacons detection installed in the infrastructure. A visual servoing system coupled with an automatic controller allows the vehicle to dock accurately to the recharging booth in a street parking area. The results show good behavior of the implemented system, which is currently deployed as a real prototype system in the city of Paris.

Proximity Operations and Docking Sensor Development

NASA Technical Reports Server (NTRS)

Howard, Richard T.; Bryan, Thomas C.; Brewster, Linda L.; Lee, James E.

2009-01-01

The Next Generation Advanced Video Guidance Sensor (NGAVGS) has been under development for the last three years as a long-range proximity operations and docking sensor for use in an Automated Rendezvous and Docking (AR&D) system. The first autonomous rendezvous and docking in the history of the U.S. Space Program was successfully accomplished by Orbital Express, using the Advanced Video Guidance Sensor (AVGS) as the primary docking sensor. That flight proved that the United States now has a mature and flight proven sensor technology for supporting Crew Exploration Vehicles (CEV) and Commercial Orbital Transport Systems (COTS) Automated Rendezvous and Docking (AR&D). NASA video sensors have worked well in the past: the AVGS used on the Demonstration of Autonomous Rendezvous Technology (DART) mission operated successfully in spot mode out to 2 km, and the first generation rendezvous and docking sensor, the Video Guidance Sensor (VGS), was developed and successfully flown on Space Shuttle flights in 1997 and 1998. 12 Parts obsolescence issues prevent the construction of more AVGS units, and the next generation sensor was updated to allow it to support the CEV and COTS programs. The flight proven AR&D sensor has been redesigned to update parts and add additional capabilities for CEV and COTS with the development of the Next Generation AVGS at the Marshall Space Flight Center. The obsolete imager and processor are being replaced with new radiation tolerant parts. In addition, new capabilities include greater sensor range, auto ranging capability, and real-time video output. This paper presents some sensor hardware trades, use of highly integrated laser components, and addresses the needs of future vehicles that may rendezvous and dock with the International Space Station (ISS) and other Constellation vehicles. It also discusses approaches for upgrading AVGS to address parts obsolescence, and concepts for minimizing the sensor footprint, weight, and power requirements. In addition, the testing of the brassboard and proto-type NGAVGS units will be discussed along with the use of the NGAVGS as a proximity operations and docking sensor.

A Steric-inhibition model for regulation of nucleotide exchange via the Dock180 family of GEFs.

PubMed

Lu, Mingjian; Kinchen, Jason M; Rossman, Kent L; Grimsley, Cynthia; Hall, Matthew; Sondek, John; Hengartner, Michael O; Yajnik, Vijay; Ravichandran, Kodi S

2005-02-22

CDM (CED-5, Dock180, Myoblast city) family members have been recently identified as novel, evolutionarily conserved guanine nucleotide exchange factors (GEFs) for Rho-family GTPases . They regulate multiple processes, including embryonic development, cell migration, apoptotic-cell engulfment, tumor invasion, and HIV-1 infection, in diverse model systems . However, the mechanism(s) of regulation of CDM proteins has not been well understood. Here, our studies on the prototype member Dock180 reveal a steric-inhibition model for regulating the Dock180 family of GEFs. At basal state, the N-terminal SH3 domain of Dock180 binds to the distant catalytic Docker domain and negatively regulates the function of Dock180. Further studies revealed that the SH3:Docker interaction sterically blocks Rac access to the Docker domain. Interestingly, ELMO binding to the SH3 domain of Dock180 disrupted the SH3:Docker interaction, facilitated Rac access to the Docker domain, and contributed to the GEF activity of the Dock180/ELMO complex. Additional genetic rescue studies in C. elegans suggested that the regulation of the Docker-domain-mediated GEF activity by the SH3 domain and its adjoining region is evolutionarily conserved. This steric-inhibition model may be a general mechanism for regulating multiple SH3-domain-containing Dock180 family members and may have implications for a variety of biological processes.

Laser space rendezvous and docking tradeoff

NASA Technical Reports Server (NTRS)

Adelman, S.; Levinson, S.; Raber, P.; Weindling, F.

1974-01-01

A spaceborne laser radar (LADAR) was configured to meet the requirements for rendezvous and docking with a cooperative object in synchronous orbit. The LADAR, configurated using existing pulsed CO2 laser technology and a 1980 system technology baseline, is well suited for the envisioned space tug missions. The performance of a family of candidate LADARS was analyzed. Tradeoff studies as a function of size, weight, and power consumption were carried out for maximum ranges of 50, 100, 200, and 300 nautical miles. The investigation supports the original contention that a rendezvous and docking LADAR can be constructed to offer a cost effective and reliable solution to the envisioned space missions. In fact, the CO2 ladar system offers distinct advantages over other candidate systems.

STS-79 payload SPACEHAB in PCR at LC39A

NASA Technical Reports Server (NTRS)

1996-01-01

Workers in the Payload Changeout Room (PCR) at Launch Pad 39A are preparing to close the payload doors for flight on the Space Shuttle Atlantis, targeted for liftoff on Mission STS-79 around September 12. The SPACEHAB Double Module located in the aft area of the payload bay is filled with supplies that will be transferred to the Russian Space Station Mir. STS-79 marks the second flight of a SPACEHAB in support of the Shuttle-Mir dockings, and the first flight of the double-module configuration. The SPACEHAB is connected by tunnel to the Orbiter Docking System (ODS), with the Androgynous Peripheral Docking System (APDS) clearly visible on top of the ODS. The APDS provides the docking interface for the linkup with Mir, while the ODS provides a passageway from the orbiter to the Russian space station and the SPACEHAB.

STS-79 SPACEHAB Double module in Payload Bay

NASA Technical Reports Server (NTRS)

1996-01-01

Workers in the Payload Changeout Room (PCR) at Launch Pad 39A are preparing to close the payload doors for flight on the Space Shuttle Atlantis, targeted for liftoff on Mission STS-79 around September 12. The payloads in Atlantis' cargo bay will play key roles during the upcoming spaceflight, which will be highlighted by the fourth docking between the U.S. Shuttle and Russian Space Station Mir. Located in the aft (lowermost) area of the payload bay is the SPACEHAB Double Module, filled with supplies and other items slated for transfer to the Russian Space Station Mir as well as research equipment. The SPACEHAB is connected by tunnel to the Orbiter Docking System (ODS). This view looks directly at the top of the ODS and shows clearly the Androgynous Peripheral Docking System (APDS) that interfaces with the Docking Module on Mir to achieve a linkup.

Approach range and velocity determination using laser sensors and retroreflector targets

NASA Technical Reports Server (NTRS)

Donovan, William J.

1991-01-01

A laser docking sensor study is currently in the third year of development. The design concept is considered to be validated. The concept is based on using standard radar techniques to provide range, velocity, and bearing information. Multiple targets are utilized to provide relative attitude data. The design requirements were to utilize existing space-qualifiable technology and require low system power, weight, and size yet, operate from 0.3 to 150 meters with a range accuracy greater than 3 millimeters and a range rate accuracy greater than 3 mm per second. The field of regard for the system is +/- 20 deg. The transmitter and receiver design features a diode laser, microlens beam steering, and power control as a function of range. The target design consists of five target sets, each having seven 3-inch retroreflectors, arranged around the docking port. The target map is stored in the sensor memory. Phase detection is used for ranging, with the frequency range-optimized. Coarse bearing measurement is provided by the scanning system (one set of binary optics) angle. Fine bearing measurement is provided by a quad detector. A MIL-STD-1750 A/B computer is used for processing. Initial test results indicate a probability of detection greater than 99 percent and a probability of false alarm less than 0.0001. The functional system is currently at the MIT/Lincoln Lab for demonstration.

Progress 37P on approach to the ISS

NASA Image and Video Library

2010-05-01

ISS023-E-030552 (1 May 2010) --- An unpiloted ISS Progress resupply vehicle approaches the International Space Station, bringing 2.6 tons of food, fuel, oxygen, propellant and supplies for the Expedition 23 crew members aboard the station. Progress 37 docked to the Pirs Docking Compartment at 2:30 p.m. (EDT) on May 1, 2010, after a three-day flight from the Baikonur Cosmodrome in Kazakhstan. The docking was conducted by Russian cosmonaut Oleg Kotov, commander, in manual control through the TORU (telerobotically operated) rendezvous system due to a jet failure on the Progress that forced a shutdown of the Kurs automated rendezvous system.

Progress 37P on approach to the ISS

NASA Image and Video Library

2010-05-01

ISS023-E-030578 (1 May 2010) --- An unpiloted ISS Progress resupply vehicle approaches the International Space Station, bringing 2.6 tons of food, fuel, oxygen, propellant and supplies for the Expedition 23 crew members aboard the station. Progress 37 docked to the Pirs Docking Compartment at 2:30 p.m. (EDT) on May 1, 2010, after a three-day flight from the Baikonur Cosmodrome in Kazakhstan. The docking was conducted by Russian cosmonaut Oleg Kotov, commander, in manual control through the TORU (telerobotically operated) rendezvous system due to a jet failure on the Progress that forced a shutdown of the Kurs automated rendezvous system.

Progress 37P on approach to the ISS

NASA Image and Video Library

2010-05-01

ISS023-E-030563 (1 May 2010) --- An unpiloted ISS Progress resupply vehicle approaches the International Space Station, bringing 2.6 tons of food, fuel, oxygen, propellant and supplies for the Expedition 23 crew members aboard the station. Progress 37 docked to the Pirs Docking Compartment at 2:30 p.m. (EDT) on May 1, 2010, after a three-day flight from the Baikonur Cosmodrome in Kazakhstan. The docking was conducted by Russian cosmonaut Oleg Kotov, commander, in manual control through the TORU (telerobotically operated) rendezvous system due to a jet failure on the Progress that forced a shutdown of the Kurs automated rendezvous system.

Progress 37P on approach to the ISS

NASA Image and Video Library

2010-05-01

ISS023-E-030460 (1 May 2010) --- An unpiloted ISS Progress resupply vehicle approaches the International Space Station, bringing 2.6 tons of food, fuel, oxygen, propellant and supplies for the Expedition 23 crew members aboard the station. Progress 37 docked to the Pirs Docking Compartment at 2:30 p.m. (EDT) on May 1, 2010, after a three-day flight from the Baikonur Cosmodrome in Kazakhstan. The docking was conducted by Russian cosmonaut Oleg Kotov, commander, in manual control through the TORU (telerobotically operated) rendezvous system due to a jet failure on the Progress that forced a shutdown of the Kurs automated rendezvous system.

Progress 37P on approach to the ISS

NASA Image and Video Library

2010-05-01

ISS023-E-030445 (1 May 2010) --- An unpiloted ISS Progress resupply vehicle approaches the International Space Station, bringing 2.6 tons of food, fuel, oxygen, propellant and supplies for the Expedition 23 crew members aboard the station. Progress 37 docked to the Pirs Docking Compartment at 2:30 p.m. (EDT) on May 1, 2010, after a three-day flight from the Baikonur Cosmodrome in Kazakhstan. The docking was conducted by Russian cosmonaut Oleg Kotov, commander, in manual control through the TORU (telerobotically operated) rendezvous system due to a jet failure on the Progress that forced a shutdown of the Kurs automated rendezvous system.

Progress 37P on approach to the ISS

NASA Image and Video Library

2010-05-01

ISS023-E-030584 (1 May 2010) --- An unpiloted ISS Progress resupply vehicle approaches the International Space Station, bringing 2.6 tons of food, fuel, oxygen, propellant and supplies for the Expedition 23 crew members aboard the station. Progress 37 docked to the Pirs Docking Compartment at 2:30 p.m. (EDT) on May 1, 2010, after a three-day flight from the Baikonur Cosmodrome in Kazakhstan. The docking was conducted by Russian cosmonaut Oleg Kotov, commander, in manual control through the TORU (telerobotically operated) rendezvous system due to a jet failure on the Progress that forced a shutdown of the Kurs automated rendezvous system.

Progress 37P on approach to the ISS

NASA Image and Video Library

2010-05-01

ISS023-E-030444 (1 May 2010) --- An unpiloted ISS Progress resupply vehicle approaches the International Space Station, bringing 2.6 tons of food, fuel, oxygen, propellant and supplies for the Expedition 23 crew members aboard the station. Progress 37 docked to the Pirs Docking Compartment at 2:30 p.m. (EDT) on May 1, 2010, after a three-day flight from the Baikonur Cosmodrome in Kazakhstan. The docking was conducted by Russian cosmonaut Oleg Kotov, commander, in manual control through the TORU (telerobotically operated) rendezvous system due to a jet failure on the Progress that forced a shutdown of the Kurs automated rendezvous system.

Progress 37P on approach to the ISS

NASA Image and Video Library

2010-05-01

ISS023-E-030528 (1 May 2010) --- An unpiloted ISS Progress resupply vehicle approaches the International Space Station, bringing 2.6 tons of food, fuel, oxygen, propellant and supplies for the Expedition 23 crew members aboard the station. Progress 37 docked to the Pirs Docking Compartment at 2:30 p.m. (EDT) on May 1, 2010, after a three-day flight from the Baikonur Cosmodrome in Kazakhstan. The docking was conducted by Russian cosmonaut Oleg Kotov, commander, in manual control through the TORU (telerobotically operated) rendezvous system due to a jet failure on the Progress that forced a shutdown of the Kurs automated rendezvous system.

KSC-95PC-1324

NASA Image and Video Library

1995-09-11

CAPE CANAVERAL, Fla. -- At NASA's Kennedy Space Center in Florida, the Russian-built Docking Module is lowered for installation into the payload bay of the space shuttle Atlantis while it is in bay 2 of the Orbiter Processing Facility. The module will fly as a primary payload on the second Space Shuttle/Mir space station docking mission, STS-74. During the mission, the module will first be attached with the orbiter's robot arm to the Orbiter Docking System in the payload bay of the orbiter Atlantis and then be docked with the Mir. When Atlantis undocks from the Mir, it will leave the new docking module permanently attached to the space station for use during future shuttle Mir docking missions. The new module will simplify future Shuttle linkups with Mir by improving orbiter clearances when it serves as a bridge between the two spacecraft. The white structures attached to the module's sides are solar panels that will be attached to the Mir after the conclusion of the STS-74 mission. Photo Credit: NASA

Kinetics of DNA-mediated docking reactions between vesicles tethered to supported lipid bilayers

PubMed Central

Chan, Yee-Hung M.; Lenz, Peter; Boxer, Steven G.

2007-01-01

Membrane–membrane recognition and binding are crucial in many biological processes. We report an approach to studying the dynamics of such reactions by using DNA-tethered vesicles as a general scaffold for displaying membrane components. This system was used to characterize the docking reaction between two populations of tethered vesicles that display complementary DNA. Deposition of vesicles onto a supported lipid bilayer was performed by using a microfluidic device to prevent mixing of the vesicles in bulk during sample preparation. Once tethered onto the surface, vesicles mixed via two-dimensional diffusion. DNA-mediated docking of two reacting vesicles results in their colocalization after collision and their subsequent tandem motion. Individual docking events and population kinetics were observed via epifluorescence microscopy. A lattice-diffusion simulation was implemented to extract from experimental data the probability, Pdock, that a collision leads to docking. For individual vesicles displaying small numbers of docking DNA, Pdock shows a first-order relationship with copy number as well as a strong dependence on the DNA sequence. Both trends are explained by a model that includes both tethered vesicle diffusion on the supported bilayer and docking DNA diffusion over each vesicle's surface. These results provide the basis for the application of tethered vesicles to study other membrane reactions including protein-mediated docking and fusion. PMID:18025472

8. CAR FLOAT AND TUG DOCKED AT BRIDGE NO. 11 ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

8. CAR FLOAT AND TUG DOCKED AT BRIDGE NO. 11 FROM BRIDGE NO. 9 APRON. LOOKING SOUTHEAST. - Greenville Yard, Transfer Bridge System, Port of New York/New Jersey, Upper New York Bay, Jersey City, Hudson County, NJ

Knowing when to give up: early-rejection stratagems in ligand docking

NASA Astrophysics Data System (ADS)

Skone, Gwyn; Voiculescu, Irina; Cameron, Stephen

2009-10-01

Virtual screening is an important resource in the drug discovery community, of which protein-ligand docking is a significant part. Much software has been developed for this purpose, largely by biochemists and those in related disciplines, who pursue ever more accurate representations of molecular interactions. The resulting tools, however, are very processor-intensive. This paper describes some initial results from a project to review computational chemistry techniques for docking from a non-chemistry standpoint. An abstract blueprint for protein-ligand docking using empirical scoring functions is suggested, and this is used to discuss potential improvements. By introducing computer science tactics such as lazy function evaluation, dramatic increases to throughput can and have been realized using a real-world docking program. Naturally, they can be extended to any system that approximately corresponds to the architecture outlined.

STS-74 leaves O&C Building for TCDT

NASA Technical Reports Server (NTRS)

1995-01-01

The STS-74 flight crew walks out of the Operations and Checkout Building on their way to conduct Terminal Countdown Demostration Test (TCDT) exercises while aboard the Space Shuttle orbiter Atlantis at Launch Pad 39A. They are (from right): Mission Commander Kenneth Cameron; Pilot James Halsell; and Mission Specialists William McArthur Jr., Chris Hadfield, and Jerry Ross (back). Hadfield is an international mission specialist representing the Canadian Space Agency. This flight will feature the second docking of the Space Shuttle with the Russian Mir space station. Docking operations will be conducted with the Russian-built Docking Module attached to the end of the Orbiter Docking System (ODS) located in Atlantis payload bay. The DM will be left attached to the Mir when Atlantis undocks. This module will serve as a means to improve future Shuttle-Mir docking operations.

Optimization of protein-protein docking for predicting Fc-protein interactions.

PubMed

Agostino, Mark; Mancera, Ricardo L; Ramsland, Paul A; Fernández-Recio, Juan

2016-11-01

The antibody crystallizable fragment (Fc) is recognized by effector proteins as part of the immune system. Pathogens produce proteins that bind Fc in order to subvert or evade the immune response. The structural characterization of the determinants of Fc-protein association is essential to improve our understanding of the immune system at the molecular level and to develop new therapeutic agents. Furthermore, Fc-binding peptides and proteins are frequently used to purify therapeutic antibodies. Although several structures of Fc-protein complexes are available, numerous others have not yet been determined. Protein-protein docking could be used to investigate Fc-protein complexes; however, improved approaches are necessary to efficiently model such cases. In this study, a docking-based structural bioinformatics approach is developed for predicting the structures of Fc-protein complexes. Based on the available set of X-ray structures of Fc-protein complexes, three regions of the Fc, loosely corresponding to three turns within the structure, were defined as containing the essential features for protein recognition and used as restraints to filter the initial docking search. Rescoring the filtered poses with an optimal scoring strategy provided a success rate of approximately 80% of the test cases examined within the top ranked 20 poses, compared to approximately 20% by the initial unrestrained docking. The developed docking protocol provides a significant improvement over the initial unrestrained docking and will be valuable for predicting the structures of currently undetermined Fc-protein complexes, as well as in the design of peptides and proteins that target Fc. Copyright © 2016 John Wiley & Sons, Ltd.

Tail Docking of Canine Puppies: Reassessment of the Tail's Role in Communication, the Acute Pain Caused by Docking and Interpretation of Behavioural Responses.

PubMed

Mellor, David J

2018-05-31

Laws, regulations and professional standards increasingly aim to ban or restrict non-therapeutic tail docking in canine puppies. These constraints have usually been justified by reference to loss of tail participation in communication between dogs, the acute pain presumed to be caused during docking itself, subsequent experiences of chronic pain and heightened pain sensitivity, and the occurrence of other complications. These areas are reconsidered here. First, a scientifically robust examination of the dynamic functional foundations, sensory components and key features of body language that are integral to canine communication shows that the role of the tail has been greatly underestimated. More specifically, it shows that tail behaviour is so embedded in canine communication that docking can markedly impede unambiguous interactions between different dogs and between dogs and people. These interactions include the expression of wide ranges of both negative and positive emotions, moods and intentions that are of daily significance for dog welfare. Moreover, all docked dogs may experience these impediments throughout their lives, which challenges assertions by opponents to such bans or restrictions that the tail is a dispensable appendage. Second, and in contrast, a re-examination of the sensory capacities of canine puppies reveals that they cannot consciously experience acute or chronic pain during at least the first week after birth, which is when they are usually docked. The contrary view is based on questionable between-species extrapolation of information about pain from neurologically mature newborns such as calves, lambs, piglets and human infants, which certainly can consciously experience pain in response to injury, to neurologically immature puppies which remain unconscious and therefore unable to experience pain until about two weeks after birth. Third, underpinned by the incorrect conclusion that puppies are conscious at the usual docking age, it is argued here that the well-validated human emotional drive or desire to care for and protect vulnerable young, leads observers to misread striking docking-induced behaviour as indicating that the puppies consciously experience significant acute pain and distress. Fourth, updated information reaffirms the conclusion that a significant proportion of dogs docked as puppies will subsequently experience persistent and significant chronic pain and heightened pain sensitivity. And fifth, other reported negative consequences of docking should also be considered because, although their prevalence is unclear, when they do occur they would have significant negative welfare impacts. It is argued that the present analysis strengthens the rationale for such bans or restrictions on docking of puppies by clarifying which of several justifications previously used are and are not scientifically supportable. In particular, it highlights the major roles the tail plays in canine communication, as well as the lifetime handicaps to communication caused by docking. Thus, it is concluded that non-therapeutic tail docking of puppies represents an unnecessary removal of a necessary appendage and should therefore be banned or restricted.

Companies hone in on radar-docking technology

NASA Astrophysics Data System (ADS)

Howell, Elizabeth

2009-11-01

As NASA prepares to retire the Space Shuttle next year, two private space firms have tested docking technology that could be used on the next generation of US spacecraft. In September, Canadian firm Neptec tested a new radar system on the Space Shuttle Discovery that allows spacecraft to dock more easily. Meanwhile, Space Exploration Technologies (SpaceX) based in California has revealed that it tested out a new proximity sensor, dubbed "Dragoneye", on an earlier shuttle mission in July.

36 CFR 13.1106 - Pets.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR NATIONAL PARK SYSTEM UNITS IN ALASKA Special Regulations-Glacier Bay National Park and Preserve Administrative... beach between the Bartlett Cove Public Use Dock and the National Park Service Administrative Dock; (c...

36 CFR 13.1106 - Pets.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR NATIONAL PARK SYSTEM UNITS IN ALASKA Special Regulations-Glacier Bay National Park and Preserve Administrative... beach between the Bartlett Cove Public Use Dock and the National Park Service Administrative Dock; (c...

36 CFR 13.1106 - Pets.

Code of Federal Regulations, 2014 CFR

2014-07-01

... Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR NATIONAL PARK SYSTEM UNITS IN ALASKA Special Regulations-Glacier Bay National Park and Preserve Administrative... beach between the Bartlett Cove Public Use Dock and the National Park Service Administrative Dock; (c...

Evaluation of protein docking predictions using Hex 3.1 in CAPRI rounds 1 and 2.

PubMed

Ritchie, David W

2003-07-01

This article describes and reviews our efforts using Hex 3.1 to predict the docking modes of the seven target protein-protein complexes presented in the CAPRI (Critical Assessment of Predicted Interactions) blind docking trial. For each target, the structure of at least one of the docking partners was given in its unbound form, and several of the targets involved large multimeric structures (e.g., Lactobacillus HPr kinase, hemagglutinin, bovine rotavirus VP6). Here we describe several enhancements to our original spherical polar Fourier docking correlation algorithm. For example, a novel surface sphere smothering algorithm is introduced to generate multiple local coordinate systems around the surface of a large receptor molecule, which may be used to define a small number of initial ligand-docking orientations distributed over the receptor surface. High-resolution spherical polar docking correlations are performed over the resulting receptor surface patches, and candidate docking solutions are refined by using a novel soft molecular mechanics energy minimization procedure. Overall, this approach identified two good solutions at rank 5 or less for two of the seven CAPRI complexes. Subsequent analysis of our results shows that Hex 3.1 is able to place good solutions within a list of

Advances in the treatment of explicit water molecules in docking and binding free energy calculations.

PubMed

Hu, Xiao; Maffucci, Irene; Contini, Alessandro

2018-05-13

The inclusion of direct effects mediated by water during the ligand-receptor recognition is a hot-topic of modern computational chemistry applied to drug discovery and development. Docking or virtual screening with explicit hydration is still debatable, despite the successful cases that have been presented in the last years. Indeed, how to select the water molecules that will be included in the docking process or how the included waters should be treated remain open questions. In this review, we will discuss some of the most recent methods that can be used in computational drug discovery and drug development when the effect of a single water, or of a small network of interacting waters, needs to be explicitly considered. Here, we analyse software to aid the selection, or to predict the position, of water molecules that are going to be explicitly considered in later docking studies. We also present software and protocols able to efficiently treat flexible water molecules during docking, including examples of applications. Finally, we discuss methods based on molecular dynamics simulations that can be used to integrate docking studies or to reliably and efficiently compute binding energies of ligands in presence of interfacial or bridging water molecules. Software applications aiding the design of new drugs that exploit water molecules, either as displaceable residues or as bridges to the receptor, are constantly being developed. Although further validation is needed, workflows that explicitly consider water will probably become a standard for computational drug discovery soon. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Implementation of Statistical Process Control: Evaluating the Mechanical Performance of a Candidate Silicone Elastomer Docking Seal

NASA Technical Reports Server (NTRS)

Oravec, Heather Ann; Daniels, Christopher C.

2014-01-01

The National Aeronautics and Space Administration has been developing a novel docking system to meet the requirements of future exploration missions to low-Earth orbit and beyond. A dynamic gas pressure seal is located at the main interface between the active and passive mating components of the new docking system. This seal is designed to operate in the harsh space environment, but is also to perform within strict loading requirements while maintaining an acceptable level of leak rate. In this study, a candidate silicone elastomer seal was designed, and multiple subscale test articles were manufactured for evaluation purposes. The force required to fully compress each test article at room temperature was quantified and found to be below the maximum allowable load for the docking system. However, a significant amount of scatter was observed in the test results. Due to the stochastic nature of the mechanical performance of this candidate docking seal, a statistical process control technique was implemented to isolate unusual compression behavior from typical mechanical performance. The results of this statistical analysis indicated a lack of process control, suggesting a variation in the manufacturing phase of the process. Further investigation revealed that changes in the manufacturing molding process had occurred which may have influenced the mechanical performance of the seal. This knowledge improves the chance of this and future space seals to satisfy or exceed design specifications.

Operator learning effects in teleoperated rendezvous & docking

NASA Astrophysics Data System (ADS)

Wilde, M.; Harder, J.; Purschke, R.

Teleoperation of spacecraft proximity operations and docking requires delicate timing and coordination of spacecraft maneuvers. Experience has shown that human operators show large performance fluctuations in these areas, which are a major factor to be addressed in operator training. In order to allow the quantification of the impact of these human fluctuations on control system performance and the human perception of this performance, a learning curve study was conducted with teleoperated final approach and docking scenarios. Over a period of ten experiment days, three test participants were tasked with repeatedly completing a set of three training scenarios. The scenarios were designed to contain different combinations of the major elements of any final approach and docking situation, and to feature an increasing difficulty level. The individual difficulty levels for the three operators furthermore differed in the level of operator support functions available in their human-machine interfaces. Operator performance in the test scenarios were evaluated in the fields approach success and precision, docking safety, and approach efficiency by a combination of recorded maneuver data and questionnaires. The results show that operator experience and the associated learning curves increase operator performance substantially, regardless of the support system used. The paper also shows that the fluctuations in operator performance and self-perception are substantial between as well as within experiment days, and must be reckoned with in teleoperation system design and mission planning.

Description of the docking module ECS for the Apollo-Soyuz Test Project.

NASA Technical Reports Server (NTRS)

Guy, W. W.; Jaax, J. R.

1973-01-01

The role of the Docking Module ECS (Environmental Control System) to be used on the Apollo-Soyuz Test mission is to provide a means for crewmen to transfer safely between the Apollo and Soyuz vehicles in a shirtsleeve environment. This paper describes the Docking Module ECS and includes the philosophy and rationale used in evaluating and selecting the capabilities that are required to satisfy the Docking Module's airlock function: (1) adjusting the pressure and composition of the atmosphere to effect crew transfer and (2) providing a shirtsleeve environment during transfer operations. An analytical evaluation is given of the environmental parameters (including CO2 level, humidity, and temperature) during a normal transfer timeline.

One Year Crew Docking to the International Space Station

NASA Image and Video Library

2015-05-27

This video was taken by the crew members aboard the Soyuz TMA-16M spacecraft which docked to the International Space Station at 9:33 p.m. EDT March 27, 2015. NASA astronaut Scott Kelly and Russian cosmonauts Mikhail Kornienko and Gennady Padalka arrived just six hours after launching from Baikonur, Kazakhstan, completing four orbits around the Earth before catching up with the orbiting laboratory. The vehicle docked to the Poisk module (also known as the Mini-Research Module 2) on the space-facing side of the Russian Service Module. The spinning object in view is an antenna that is part of the automatic rendezvous and docking system known as KURS.

Efficient Relaxation of Protein-Protein Interfaces by Discrete Molecular Dynamics Simulations.

PubMed

Emperador, Agusti; Solernou, Albert; Sfriso, Pedro; Pons, Carles; Gelpi, Josep Lluis; Fernandez-Recio, Juan; Orozco, Modesto

2013-02-12

Protein-protein interactions are responsible for the transfer of information inside the cell and represent one of the most interesting research fields in structural biology. Unfortunately, after decades of intense research, experimental approaches still have difficulties in providing 3D structures for the hundreds of thousands of interactions formed between the different proteins in a living organism. The use of theoretical approaches like docking aims to complement experimental efforts to represent the structure of the protein interactome. However, we cannot ignore that current methods have limitations due to problems of sampling of the protein-protein conformational space and the lack of accuracy of available force fields. Cases that are especially difficult for prediction are those in which complex formation implies a non-negligible change in the conformation of the interacting proteins, i.e., those cases where protein flexibility plays a key role in protein-protein docking. In this work, we present a new approach to treat flexibility in docking by global structural relaxation based on ultrafast discrete molecular dynamics. On a standard benchmark of protein complexes, the method provides a general improvement over the results obtained by rigid docking. The method is especially efficient in cases with large conformational changes upon binding, in which structure relaxation with discrete molecular dynamics leads to a predictive success rate double that obtained with state-of-the-art rigid-body docking.

Synthesis, stereochemistry, crystal structure, docking study and biological evaluation of some new N-benzylpiperidin-4-ones

NASA Astrophysics Data System (ADS)

Ponnuswamy, S.; Kayalvizhi, R.; Sethuvasan, S.; Sugumar, P.; Ponnuswamy, M. N.

2018-03-01

Two new N-benzylpiperidin-4-ones 3 and 4 have been synthesized and characterized using IR, 1D and 2D NMR spectral studies. The NMR data of N-benzylpiperidin-4-ones 3 and 4 reveal that the compounds prefer to exist in chair conformation with equatorial orientation of the bulky substituents and the single crystal X-ray structure of compound 4 also reveals a similar conformation in solid state. Furthermore, the antimicrobial studies carried out for the compounds 1-4 indicate moderate activities with the selected strains. The antioxidant potency of 3 is superior whereas 4 exhibits moderate activity when compared to that of standard drug. The results of molecular docking studies with the AmpC β-lactamase enzyme indicate that compound 3 shows better docking score and binding energy than the co-crystal ligand.

Saturn Apollo Program

NASA Image and Video Library

1976-06-01

This illustration depicts the launch configuration of the Apollo spacecraft for the Apollo-Soyuz Test Project (ASTP). The ASTP was the first international docking of the U.S.'s Apollo spacecraft and the U.S.S.R.'s Soyuz spacecraft in space. A joint engineering team from the two countries met to develop a docking system that permitted the two spacecraft to link in space and allowed the two crews to travel from one spacecraft to the other. This system entailed developing a large habitable Docking Module (DM) to be carried on the Apollo spacecraft to facilitate the joining of two dissimilar spacecraft. The Marshall Space Flight Center was responsible for development and sustaining engineering of the Saturn IB launch vehicle during the mission.

SPACEHAB module at LC-39B for STS-76

NASA Technical Reports Server (NTRS)

1996-01-01

At Launch Pad 39B, the SPACEHAB module has been installed in the payload bay of the Space Shuttle Atlantis, which was rolled out to the pad a day previously. Already located in the payload bay was the Orbiter Docking System (ODS), to which the SPACEHAB was connected via a tunnel. During the upcoming flight of Atlantis on Mission STS-76, the ODS will be docked to the Docking Module located on the Kristall module docking port on the Russian Space Station Mir. The SPACEHAB will be filled with Russian and U.S. logistics equipment for transfer to Mir. Also located in the mini-research laboratory is the European Space Agency's Biorack, which houses experiments to be conducted by the U.S. astronauts during the nine-day flight. Atlantis is scheduled to lift off on the third Shuttle-Mir docking mission on March 21.

Compodock, a new device for sterile docking.

PubMed

van Der Meer, P F; Biekart, F T; Pietersz, R N; Rebers, S P; Reesink, H W

2000-06-01

A new device for sterile docking, the Compodock (Fresenius NPBI Transfusion Technology), was developed for connecting PVC tubing for medical use while maintaining sterility. Sterility of the connections was assessed by welding tubing with a heavy exterior contamination with Bacillus subtilis spores and also by welding in an environment contaminated with aerosols of B. subtilis. Tubing was either dry or liquid-filled ("wet") and had various diameters. Bacterial culture medium was flushed through the welded area and subsequently cultured. Tensile strength was measured, and, under semi-routine conditions, Compodock was tested for user friendliness and speed. None of the cultures of welded tubing with exterior contamination showed growth, neither the dry-dry (n = 434) nor the wet-wet connections (n = 622). Cultures were also negative for welds made in the contaminated environment (dry-dry, 67; wet-wet, 55). Tensile strength complied fully with ISO 3826 standards (that is, a force of 20 newtons [N] for 15 sec), with a mean maximal strength ranging from 73 to 100 N, depending on diameter and content of the tubing. The semi-routine handling was regarded as good: welds were easily opened; there were clear instructions and error warnings; and the processing time averaged 52 seconds. The Compodock is able to maintain a functionally closed system, with maintenance of sterility, despite heavy exterior bacterial contamination; tensile strength conformed to ISO standards. Compodock is suitable for routine implementation in the blood bank.

Artist concept illustrating key events on day by day basis during Apollo 9

NASA Technical Reports Server (NTRS)

1969-01-01

Artist concept illustrating key events on day by day basis during Apollo 9 mission. First photograph illustrates activities on the first day of the mission, including flight crew preparation, orbital insertion, 103 north mile orbit, separations, docking and docked Service Propulsion System Burn (19792); Second day events include landmark tracking, pitch maneuver, yaw-roll maneuver, and high apogee orbits (19793); Third day events include crew transfer and Lunar Module system evaluation (19794); Fourth day events include use of camera, day-night extravehicular activity, use of golden slippers, and television over Texas and Louisiana (19795); Fifth day events include vehicles undocked, Lunar Module burns for rendezvous, maximum separation, ascent propulsion system burn, formation flying and docking, and Lunar Module jettison ascent burn (19796); Sixth thru ninth day events include service propulsion system burns and landmark sightings, photograph special tests (19797); Tenth day events i

Experimental validation of docking and capture using space robotics testbeds

NASA Technical Reports Server (NTRS)

Spofford, John; Schmitz, Eric; Hoff, William

1991-01-01

This presentation describes the application of robotic and computer vision systems to validate docking and capture operations for space cargo transfer vehicles. Three applications are discussed: (1) air bearing systems in two dimensions that yield high quality free-flying, flexible, and contact dynamics; (2) validation of docking mechanisms with misalignment and target dynamics; and (3) computer vision technology for target location and real-time tracking. All the testbeds are supported by a network of engineering workstations for dynamic and controls analyses. Dynamic simulation of multibody rigid and elastic systems are performed with the TREETOPS code. MATRIXx/System-Build and PRO-MATLAB/Simulab are the tools for control design and analysis using classical and modern techniques such as H-infinity and LQG/LTR. SANDY is a general design tool to optimize numerically a multivariable robust compensator with a user-defined structure. Mathematica and Macsyma are used to derive symbolically dynamic and kinematic equations.

Towards a standardized grasping and refuelling on-orbit servicing for geo spacecraft

NASA Astrophysics Data System (ADS)

Medina, Alberto; Tomassini, Angelo; Suatoni, Matteo; Avilés, Marcos; Solway, Nick; Coxhill, Ian; Paraskevas, Iosif S.; Rekleitis, Georgios; Papadopoulos, Evangelos; Krenn, Rainer; Brito, André; Sabbatinelli, Beatrice; Wollenhaupt, Birk; Vidal, Christian; Aziz, Sarmad; Visentin, Gianfranco

2017-05-01

Exploitation of space must benefit from the latest advances in robotics. On-orbit servicing is a clear candidate for the application of autonomous rendezvous and docking mechanisms. However, during the last three decades most of the trials took place combining extravehicular activities (EVAs) with telemanipulated robotic arms. The European Space Agency (ESA) considers that grasping and refuelling are promising near-mid-term capabilities that could be performed by servicing spacecraft. Minimal add-ons on spacecraft to enhance their serviceability may protect them for a changing future in which satellite servicing may become mainstream. ESA aims to conceive and promote standard refuelling provisions that can be installed in present and future European commercial geostationary orbit (GEO) satellite platforms and scientific spacecraft. For this purpose ESA has started the ASSIST activity addressing the analysis, design and validation of internal provisions (such as modifications to fuel, gas, electrical and data architecture to allow servicing) and external provisions (such as integrated berthing fixtures with peripheral electrical, gas, liquid connectors, leak check systems and corresponding optical and radio markers for cooperative rendezvous and docking). This refuelling approach is being agreed with European industry (OHB, Thales Alenia Space) and expected to be consolidated with European commercial operators as a first step to become an international standard; this approach is also being considered for on-orbit servicing spacecraft, such as the SpaceTug, by Airbus DS. This paper describes in detail the operational means, structure, geometry and accommodation of the system. Internal and external provisions will be designed with the minimum possible impact on the current architecture of GEO satellites without introducing additional risks in the development and commissioning of the satellite. End-effector and berthing fixtures are being designed in the range of few kilos and linear dimensions around 15 cm. A central mechanical part is expected to perform first a soft docking followed by a motorized retraction ending during a hard docking phase using aligning pins. Mating and de-mating will be exhaustively analysed to ensure robustness of operations. Leakage-free valves would allow for the transfer of fuel to the serviced spacecraft. The validation of the ASSIST system through dedicated environmental tests in a vacuum chamber together with dynamic testing using an air-bearing table will allow for the demonstration of concept feasibility and its suitability for becoming a standard of the on-orbit space industry. Failure during the injection of the payload into the nominal target or transfer orbit. In most cases the satellite cannot accomplish this on its own; an orbit transfer vehicle could provide support. Necessity for support unfinished operations during the test and commissioning phase. Typical example can be incomplete deployment mechanism of solar arrays or of antenna dishes. Premature end of life of the satellite due to equipment obsolescence or wear. Extension of the expected duration of the satellite operative life through a refuelling of propellant tanks devoted to attitude/orbit control. This scenario will be the main subject of this ASSIST project and will be fully explored. This activity is led by GMV (coordinator and dynamics simulator) together with MOOG (mechanical design, breadboard manufacturing and environmental testing), NTUA (air-bearing table dynamics and testing), DLR (contact dynamics), OHB (mission requirements and propulsion provisions) and TAS (mission requirements).This paper is organized as follows: Section 1 provides an introduction, Section 2 introduces the ASSIST concept, Section 3 provides a review on servicing/refuelling systems, Section 4 describes the operational scenarios and phases, Section 5 presents the ASSIST design while Section 6 describes the step-by-step refuelling operations, Sections 7 and 8 present the internal and external provisions respectively, Section 9 introduces the Kinematic and Dynamic simulator, Section 10 shows the air-bearing test set-up, Section 11 describes the dynamic test cases and validation results and finally Sections 12 present the conclusions.

Automated docking of ligands to an artificial active site: augmenting crystallographic analysis with computer modeling

NASA Astrophysics Data System (ADS)

Rosenfeld, Robin J.; Goodsell, David S.; Musah, Rabi A.; Morris, Garrett M.; Goodin, David B.; Olson, Arthur J.

2003-08-01

The W191G cavity of cytochrome c peroxidase is useful as a model system for introducing small molecule oxidation in an artificially created cavity. A set of small, cyclic, organic cations was previously shown to bind in the buried, solvent-filled pocket created by the W191G mutation. We docked these ligands and a set of non-binders in the W191G cavity using AutoDock 3.0. For the ligands, we compared docking predictions with experimentally determined binding energies and X-ray crystal structure complexes. For the ligands, predicted binding energies differed from measured values by ± 0.8 kcal/mol. For most ligands, the docking simulation clearly predicted a single binding mode that matched the crystallographic binding mode within 1.0 Å RMSD. For 2 ligands, where the docking procedure yielded an ambiguous result, solutions matching the crystallographic result could be obtained by including an additional crystallographically observed water molecule in the protein model. For the remaining 2 ligands, docking indicated multiple binding modes, consistent with the original electron density, suggesting disordered binding of these ligands. Visual inspection of the atomic affinity grid maps used in docking calculations revealed two patches of high affinity for hydrogen bond donating groups. Multiple solutions are predicted as these two sites compete for polar hydrogens in the ligand during the docking simulation. Ligands could be distinguished, to some extent, from non-binders using a combination of two trends: predicted binding energy and level of clustering. In summary, AutoDock 3.0 appears to be useful in predicting key structural and energetic features of ligand binding in the W191G cavity.

MOLA: a bootable, self-configuring system for virtual screening using AutoDock4/Vina on computer clusters.

PubMed

Abreu, Rui Mv; Froufe, Hugo Jc; Queiroz, Maria João Rp; Ferreira, Isabel Cfr

2010-10-28

Virtual screening of small molecules using molecular docking has become an important tool in drug discovery. However, large scale virtual screening is time demanding and usually requires dedicated computer clusters. There are a number of software tools that perform virtual screening using AutoDock4 but they require access to dedicated Linux computer clusters. Also no software is available for performing virtual screening with Vina using computer clusters. In this paper we present MOLA, an easy-to-use graphical user interface tool that automates parallel virtual screening using AutoDock4 and/or Vina in bootable non-dedicated computer clusters. MOLA automates several tasks including: ligand preparation, parallel AutoDock4/Vina jobs distribution and result analysis. When the virtual screening project finishes, an open-office spreadsheet file opens with the ligands ranked by binding energy and distance to the active site. All results files can automatically be recorded on an USB-flash drive or on the hard-disk drive using VirtualBox. MOLA works inside a customized Live CD GNU/Linux operating system, developed by us, that bypass the original operating system installed on the computers used in the cluster. This operating system boots from a CD on the master node and then clusters other computers as slave nodes via ethernet connections. MOLA is an ideal virtual screening tool for non-experienced users, with a limited number of multi-platform heterogeneous computers available and no access to dedicated Linux computer clusters. When a virtual screening project finishes, the computers can just be restarted to their original operating system. The originality of MOLA lies on the fact that, any platform-independent computer available can he added to the cluster, without ever using the computer hard-disk drive and without interfering with the installed operating system. With a cluster of 10 processors, and a potential maximum speed-up of 10x, the parallel algorithm of MOLA performed with a speed-up of 8,64× using AutoDock4 and 8,60× using Vina.

Synthesis, spectroscopic analyses, chemical reactivity and molecular docking study and anti-tubercular activity of pyrazine and condensed oxadiazole derivatives

NASA Astrophysics Data System (ADS)

Al-Tamimi, Abdul-Malek S.; Mary, Y. Sheena; Miniyar, Pankaj B.; Al-Wahaibi, Lamya H.; El-Emam, Ali A.; Armaković, Stevan; Armaković, Sanja J.

2018-07-01

The FT-IR spectral analysis and theoretical calculations of the wavenumbers of three oxadiazole derivatives, 2-(5-(2-chlorophenyl)-1,3,4-oxadiazol-2-yl)pyrazine (ORTHOPHPZ), 2-(5-(3-chlorophenyl)-1,3,4-oxadiazol-2-yl)pyrazine (METAPHPZ) and 2-(5-(4-chlorophenyl)-1,3,4-oxadiazol-2-yl)pyrazine (PARAPHPZ) were reported in the present work. The theoretically predicted values of polarizability give the nonlinear behaviour of the compounds. The frontier molecular orbital analysis show the chemical stability of the title compounds and the NBO analysis gives the interactions in the molecular systems. Understanding of reactivity of newly synthetiszed oxadiazole derivatives in this study has been achieved thanks to combination of density functional theory (DFT) calculations, molecular dynamics (MD) simulations and molecular docking procedures. New oxadiazole derivatives have also been characterized experimentally through FT-IR and NMR approaches, thanks to which detailed structural properties have been understood. Both global and local reactivity properties have been investigated by calculations of quantum molecular descriptors such as molecular electrostatic potential (MEP), local average ionization energy (ALIE), Fukui functions, bond dissociation energies for hydrogen abstraction (H-BDE), radial distribution functions and binding energies of ligand against selected protein. The first hyperpolarizabilities of ORTHOPHPZ, METAPHPZ and PARAPHPZ are respectively, 84.62, 94.71 and 184.10 times that of urea. The docked ligands form stable complexes with the receptor 1-phosphatidylinositol phosphodiesterase and the results suggest that these compounds can be developed as new anti-cancer drugs. The anti-TB activity of PM series against M. tuberculosis H37RV strain was performed by Middlebrooke 7H-9 method. The compounds, ORTHOPHPZ, METAPHPZ and PARAPHPZ were moderately active between 25 and 50 μg/ml concentration as compared with the standard anti-TB agents and the -log MIC activity was found in the range of 1.011-1.274 as compared with isoniazid (INH) (1.137) and pyrazinamide (PZA) (1.115) standard anti-TB agents.

Supervised autonomous rendezvous and docking system technology evaluation

NASA Technical Reports Server (NTRS)

Marzwell, Neville I.

1991-01-01

Technology for manned space flight is mature and has an extensive history of the use of man-in-the-loop rendezvous and docking, but there is no history of automated rendezvous and docking. Sensors exist that can operate in the space environment. The Shuttle radar can be used for ranges down to 30 meters, Japan and France are developing laser rangers, and considerable work is going on in the U.S. However, there is a need to validate a flight qualified sensor for the range of 30 meters to contact. The number of targets and illumination patterns should be minimized to reduce operation constraints with one or more sensors integrated into a robust system for autonomous operation. To achieve system redundancy, it is worthwhile to follow a parallel development of qualifying and extending the range of the 0-12 meter MSFC sensor and to simultaneously qualify the 0-30(+) meter JPL laser ranging system as an additional sensor with overlapping capabilities. Such an approach offers a redundant sensor suite for autonomous rendezvous and docking. The development should include the optimization of integrated sensory systems, packaging, mission envelopes, and computer image processing to mimic brain perception and real-time response. The benefits of the Global Positioning System in providing real-time positioning data of high accuracy must be incorporated into the design. The use of GPS-derived attitude data should be investigated further and validated.

Apollo-Soyuz Test Project (ASTP)

NASA Technical Reports Server (NTRS)

1974-01-01

This artist's concept depicts the Apollo-Soyuz Test Project (ASTP) with insets of photographs of three U.S. astronauts (Thomas Stafford, Vance Brand, and Donald Slayton) and two U.S.S.R. cosmonauts (Alexei Leonov and Valeri Kubasov). The objective of the ASTP mission was to accomplish the first docking of a standardized international system, the U.S.'s Apollo spacecraft and the U.S.S.R.'s Soyuz spacecraft, in space. The Soyuz spacecraft was launched from the Baikonur Cosmodrome near Tyuratam in the Kazakh, Soviet Socialist Republic, at 8:20 a.m. (EDT) on July 15, 1975. The Apollo spacecraft was launched from Launch Complex 39B, Kennedy Space Center, Florida, at 3:50 p.m. (EDT) on July 15, 1975. The Primary objectives of the ASTP were achieved. They performed spacecraft rendezvous, docking and undocking, conducted intervehicular crew transfer, and demonstrated the interaction of U.S. and U.S.S.R. control centers and spacecraft crews. The mission marked the last use of a Saturn launch vehicle. The Marshall Space Flight Center was responsible for development and sustaining engineering of the Saturn IB launch vehicle during the mission.

GENERAL VIEW OF FLIGHT LINE BUILDINGS. FROM LEFT TO RIGHT, ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

GENERAL VIEW OF FLIGHT LINE BUILDINGS. FROM LEFT TO RIGHT, JET ENGINE TEST CELL BUILDING (BUILDING 2820), MAINTENANCE DOCK, FLIGHT SYSTEM (BUILDING 2818)" AND MAINTENANCE DOCK (BUILDING 2793). VIEW TO SOUTHEAST - Plattsburgh Air Force Base, U.S. Route 9, Plattsburgh, Clinton County, NY

Insight into the da Vinci® Xi - technical notes for single-docking left-sided colorectal procedures.

PubMed

Ngu, James Chi-Yong; Sim, Sarah; Yusof, Sulaiman; Ng, Chee-Yung; Wong, Andrew Siang-Yih

2017-12-01

The adoption of robot-assisted laparoscopic colorectal surgery has been hampered by issues with docking, operative duration, technical difficulties in multi-quadrant access, and cost. The da Vinci® Xi has been designed to overcome some of these limitations. We describe our experience with the system and offer technical insights to its application in left-sided colorectal procedures. Our initial series of left-sided robotic colorectal procedures was evaluated. Patient demographics and operative outcomes were recorded prospectively using a predefined database. Between March 2015 and April 2016, 54 cases of robot-assisted laparoscopic left-sided colorectal procedures were successfully completed with no cases of conversion. The majority were low anterior resections for colorectal malignancies. Using the da Vinci® Xi Surgical System, multi-quadrant surgery involving dissection from the splenic flexure to the pelvis was possible without redocking. The da Vinci® Xi simplifies the docking procedure and makes single-docking feasible for multi-quadrant left-sided colorectal procedures. Copyright © 2016 John Wiley & Sons, Ltd.

Minimizing coal terminal marine structure costs. A case history: Plaquemines Parish terminal. [Dock and piles design to absorb and distribute impact and longitudinal forces

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pardon, D.V.; Faeth, M.T.; Curth, O.

1981-01-01

At International Marine Terminals' Plaquemines Parish Terminal, design optimization was accomplished by optimizing the dock pile bent spacing and designing the superstructure to distribute berthing impact forces and bollard pulls over a large number of pile bents. Also, by resisting all longitudinal forces acting on the dock at a single location near the center of the structure, the number of longitudinal batter piles was minimized and the need for costly expansion joints was eliminated. Computer techniques were utilized to analyze and optimize the design of the new dock. Pile driving procedures were evaluated utilizing a wave equation technique. Tripod dolphinsmore » with a resilient fender system were provided. The resilent fender system, a combination of rubber shear type and wing type fenders, adds only a small percentage to the total cost of the dolphins but greatly increases their energy absorption capability.« less

Influence of protonation, tautomeric, and stereoisomeric states on protein-ligand docking results.

PubMed

ten Brink, Tim; Exner, Thomas E

2009-06-01

In this work, we present a systematical investigation of the influence of ligand protonation states, stereoisomers, and tautomers on results obtained with the two protein-ligand docking programs GOLD and PLANTS. These different states were generated with a fully automated tool, called SPORES (Structure PrOtonation and Recognition System). First, the most probable protonations, as defined by this rule based system, were compared to the ones stored in the well-known, manually revised CCDC/ASTEX data set. Then, to investigate the influence of the ligand protonation state on the docking results, different protonation states were created. Redocking and virtual screening experiments were conducted demonstrating that both docking programs have problems in identifying the correct protomer for each complex. Therefore, a preselection of plausible protomers or the improvement of the scoring functions concerning their ability to rank different molecules/states is needed. Additionally, ligand stereoisomers were tested for a subset of the CCDC/ASTEX set, showing similar problems regarding the ranking of these stereoisomers as the ranking of the protomers.

Molecular Docking and Molecular Dynamics to Identify a Novel Human Immunodeficiency Virus Inhibitor from Alkaloids of Toddalia asiatica.

PubMed

Priya, R; Sumitha, Rajendrarao; Doss, C George Priya; Rajasekaran, C; Babu, S; Seenivasan, R; Siva, R

2015-10-01

Acquired immunodeficiency syndrome caused by human immunodeficiency virus (HIV) is an immunosuppressive disease. Over the past decades, it has plagued human health due to the grave consequences in its harness. For this reason, anti-HIV agents are imperative, and the search for the same from natural resources would assure the safety. In this investigation we have performed molecular docking, molecular property prediction, drug-likeness score, and molecular dynamics (MD) simulation to develop a novel anti-HIV drug. We have screened 12 alkaloids from a medicinal plant Toddalia asiatica for its probabilistic binding with the active site of the HIV-1-reverse transcriptase (HIV-1-RT) domain (the major contributor to the onset of the disease). The docking results were evaluated based on free energies of binding (ΔG), and the results suggested toddanol, toddanone, and toddalenone to be potent inhibitors of HIV-1-RT. In addition, the alkaloids were subjected to molecular property prediction analysis. Toddanol and toddanone with more rotatable bonds were found to have a drug-likeness score of 0.23 and 0.11, respectively. These scores were comparable with the standard anti-HIV drug zidovudine with a model score 0.28. Finally, two characteristic protein-ligand complexes were exposed to MD simulation to determine the stability of the predicted conformations. The toddanol-RT complex showed higher stability and stronger H-bonds than toddanone-RT complex. Based on these observations, we firmly believe that the alkaloid toddanol could aid in efficient HIV-1 drug discovery. In the present study, the molecular docking and MD simulations are performed to explore the possible binding mode of HIV 1 RT with 12 alkaloids of T. asiatica. Molecular docking by AutoDock4 revealed three alkaloids toddanol, toddanone, and toddalenone with highest binding affinity towards HIV 1 RT. The drug likeness model score revealed a positive score for toddanol and toddanone which is comparable to the drug likeness score of the standard anti HIV drug zidovudine. Results from simulation analysis revealed that toddanol RT complex is more stable than toddanone RT complex inferring toddanol as a potential anti HIV drug molecule. Abbreviations used: HIV: Human immunodeficiency virus, HIV 1 RT: HIV 1 reverse transcriptase, RNase H: Ribonuclease H, MD: Molecular dynamics, PDB: Protein databank, RMSD: Root mean square deviation, RMSF: Root mean square fluctuation.

Grid-based Molecular Footprint Comparison Method for Docking and De Novo Design: Application to HIVgp41

PubMed Central

Mukherjee, Sudipto; Rizzo, Robert C.

2014-01-01

Scoring functions are a critically important component of computer-aided screening methods for the identification of lead compounds during early stages of drug discovery. Here, we present a new multi-grid implementation of the footprint similarity (FPS) scoring function that was recently developed in our laboratory which has proven useful for identification of compounds which bind to a protein on a per-residue basis in a way that resembles a known reference. The grid-based FPS method is much faster than its Cartesian-space counterpart which makes it computationally tractable for on-the-fly docking, virtual screening, or de novo design. In this work, we establish that: (i) relatively few grids can be used to accurately approximate Cartesian space footprint similarity, (ii) the method yields improved success over the standard DOCK energy function for pose identification across a large test set of experimental co-crystal structures, for crossdocking, and for database enrichment, and (iii) grid-based FPS scoring can be used to tailor construction of new molecules to have specific properties, as demonstrated in a series of test cases targeting the viral protein HIVgp41. The method will be made available in the program DOCK6. PMID:23436713

Computational Insight into Protein Tyrosine Phosphatase 1B Inhibition: A Case Study of the Combined Ligand- and Structure-Based Approach.

PubMed

Zhang, Xiangyu; Jiang, Hailun; Li, Wei; Wang, Jian; Cheng, Maosheng

2017-01-01

Protein tyrosine phosphatase 1B (PTP1B) is an attractive target for treating cancer, obesity, and type 2 diabetes. In our work, the way of combined ligand- and structure-based approach was applied to analyze the characteristics of PTP1B enzyme and its interaction with competitive inhibitors. Firstly, the pharmacophore model of PTP1B inhibitors was built based on the common feature of sixteen compounds. It was found that the pharmacophore model consisted of five chemical features: one aromatic ring (R) region, two hydrophobic (H) groups, and two hydrogen bond acceptors (A). To further elucidate the binding modes of these inhibitors with PTP1B active sites, four docking programs (AutoDock 4.0, AutoDock Vina 1.0, standard precision (SP) Glide 9.7, and extra precision (XP) Glide 9.7) were used. The characteristics of the active sites were then described by the conformations of the docking results. In conclusion, a combination of various pharmacophore features and the integration information of structure activity relationship (SAR) can be used to design novel potent PTP1B inhibitors.

MEGADOCK: An All-to-All Protein-Protein Interaction Prediction System Using Tertiary Structure Data

PubMed Central

Ohue, Masahito; Matsuzaki, Yuri; Uchikoga, Nobuyuki; Ishida, Takashi; Akiyama, Yutaka

2014-01-01

The elucidation of protein-protein interaction (PPI) networks is important for understanding cellular structure and function and structure-based drug design. However, the development of an effective method to conduct exhaustive PPI screening represents a computational challenge. We have been investigating a protein docking approach based on shape complementarity and physicochemical properties. We describe here the development of the protein-protein docking software package “MEGADOCK” that samples an extremely large number of protein dockings at high speed. MEGADOCK reduces the calculation time required for docking by using several techniques such as a novel scoring function called the real Pairwise Shape Complementarity (rPSC) score. We showed that MEGADOCK is capable of exhaustive PPI screening by completing docking calculations 7.5 times faster than the conventional docking software, ZDOCK, while maintaining an acceptable level of accuracy. When MEGADOCK was applied to a subset of a general benchmark dataset to predict 120 relevant interacting pairs from 120 x 120 = 14,400 combinations of proteins, an F-measure value of 0.231 was obtained. Further, we showed that MEGADOCK can be applied to a large-scale protein-protein interaction-screening problem with accuracy better than random. When our approach is combined with parallel high-performance computing systems, it is now feasible to search and analyze protein-protein interactions while taking into account three-dimensional structures at the interactome scale. MEGADOCK is freely available at http://www.bi.cs.titech.ac.jp/megadock. PMID:23855673

Template-based protein-protein docking exploiting pairwise interfacial residue restraints.

PubMed

Xue, Li C; Rodrigues, João P G L M; Dobbs, Drena; Honavar, Vasant; Bonvin, Alexandre M J J

2017-05-01

Although many advanced and sophisticated ab initio approaches for modeling protein-protein complexes have been proposed in past decades, template-based modeling (TBM) remains the most accurate and widely used approach, given a reliable template is available. However, there are many different ways to exploit template information in the modeling process. Here, we systematically evaluate and benchmark a TBM method that uses conserved interfacial residue pairs as docking distance restraints [referred to as alpha carbon-alpha carbon (CA-CA)-guided docking]. We compare it with two other template-based protein-protein modeling approaches, including a conserved non-pairwise interfacial residue restrained docking approach [referred to as the ambiguous interaction restraint (AIR)-guided docking] and a simple superposition-based modeling approach. Our results show that, for most cases, the CA-CA-guided docking method outperforms both superposition with refinement and the AIR-guided docking method. We emphasize the superiority of the CA-CA-guided docking on cases with medium to large conformational changes, and interactions mediated through loops, tails or disordered regions. Our results also underscore the importance of a proper refinement of superimposition models to reduce steric clashes. In summary, we provide a benchmarked TBM protocol that uses conserved pairwise interface distance as restraints in generating realistic 3D protein-protein interaction models, when reliable templates are available. The described CA-CA-guided docking protocol is based on the HADDOCK platform, which allows users to incorporate additional prior knowledge of the target system to further improve the quality of the resulting models. © The Author 2016. Published by Oxford University Press.

A Design for an Orbital Assembly Facility for Complex Missions

NASA Astrophysics Data System (ADS)

Feast, S.; Bond, A.

A design is presented for an Operations Base Station (OBS) in low earth orbit that will function as an integral part of a space transportation system, enabling assembly and maintenance of a Cis-Lunar transportation infrastructure and integration of vehicles for other high energy space missions to be carried out. Construction of the OBS assumes the use of the SKYLON Single-Stage-to-Orbit (SSTO) spaceplane, which imposes design and assembly constraints due to its payload mass limits and payload bay dimensions. It is assumed that the space transport infrastructure and high mission energy vehicles would also make use of SKYLON to deploy standard transport equipment and stages bound by these same constraints. The OBS is therefore a highly modular arrangement, incorporating some of these other vehicle system elements in its layout design. Architecturally, the facilities of the OBS are centred around the Assembly Dock which is in the form of a large cylindrical spaceframe structure with two large doors on either end incorporating a skin of aluminised Mylar to enclose the dock. Longitudinal rails provide internal tether attachments to anchor vehicles and components while manipulators are used for the handling and assembling of vehicle structures. The exterior of the OBS houses the habitation modules for workforce and vehicle crews along with propellant farms and other operational facilities.

Preliminary GN&C Design for the On-Orbit Autonomous Assembly of Nanosatellite Demonstration Mission

NASA Technical Reports Server (NTRS)

Pei, Jing; Walsh, Matt; Roithmayr, Carlos; Karlgaard, Chris; Peck, Mason; Murchison, Luke

2017-01-01

Small spacecraft autonomous rendezvous and docking (ARD) is an essential technology for future space structure assembly missions. The On-orbit Autonomous Assembly of Nanosatellites (OAAN) team at NASA Langley Research Center (LaRC) intends to demonstrate the technology to autonomously dock two nanosatellites to form an integrated system. The team has developed a novel magnetic capture and latching mechanism that allows for docking of two CubeSats without precise sensors and actuators. The proposed magnetic docking hardware not only provides the means to latch the CubeSats, but it also significantly increases the likelihood of successful docking in the presence of relative attitude and position errors. The simplicity of the design allows it to be implemented on many CubeSat rendezvous missions. Prior to demonstrating the docking subsystem capabilities on orbit, the GN&C subsystem should have a robust design such that it is capable of bringing the CubeSats from an arbitrary initial separation distance of as many as a few thousand kilometers down to a few meters. The main OAAN Mission can be separated into the following phases: 1) Launch, checkout, and drift, 2) Far-Field Rendezvous or Drift Recovery, 3) Proximity Operations, 4) Docking. This paper discusses the preliminary GN&C design and simulation results for each phase of the mission.

Test - Apollo-Soyuz Test Project (ASTP)

NASA Image and Video Library

1974-07-01

S74-24671 (10 July 1974) --- Three Apollo-Soyuz Test Project (ASTP) engineers look over a Soyuz spacecraft docking system prior to an ASTP docking mechanism fitness test conducted in Building 13 at the Johnson Space Center (JSC). They are (left to right) Robert White, Vladimir Syromyatnikov and Yevgeniy Bobrov. White is the American chairman of ASTP Working Group Number 3, and Syromyatnikov is his Soviet counterpart. This working group is concerned with ASTP docking problems and procedures. White is with JSC's Spacecraft Design Division. Syromyatnikov is senior researcher of the Soviet State Research Institute of Machine Building. Bobrov is a junior researcher with the Institute of Machine Building. The joint United States - USSR ASTP docking mission in Earth orbit is scheduled for the summer of 1975.

Space station full-scale docking/berthing mechanisms development

NASA Technical Reports Server (NTRS)

Burns, Gene C.; Price, Harold A.; Buchanan, David B.

1988-01-01

One of the most critical operational functions for the space station is the orbital docking between the station and the STS orbiter. The program to design, fabricate, and test docking/berthing mechanisms for the space station is described. The design reflects space station overall requirements and consists of two mating docking mechanism halves. One half is designed for use on the shuttle orbiter and incorporates capture and energy attenuation systems using computer controlled electromechanical actuators and/or attenuators. The mating half incorporates a flexible feature to allow two degrees of freedom at the module-to-module interface of the space station pressurized habitat volumes. The design concepts developed for the prototype units may be used for the first space station flight hardware.

MMU (Manned Maneuvering Unit) Task Simulator.

DTIC Science & Technology

1986-01-15

motion is obtained by applying the Clohessy - Wiltshire equations for terminal rendezvous/docking with the earth modeled as a uniform sphere " (Aj<endix...quaternions. The Clohessy - Wiltshire equations for terminal rendezvous/docking are used to model orbital drift. These are linearized equations of...system is the Clohessy - Wiltshire system, centered at the target and described in detail in Appendix A. The earth’s vector list is scaled at one distance

Ionic liquid mediated synthesis and molecular docking study of novel aromatic embedded Schiff bases as potent cholinesterase inhibitors.

PubMed

Abd Razik, Basma M; Osman, Hasnah; Basiri, Alireza; Salhin, Abdussalam; Kia, Yalda; Ezzat, Mohammed Oday; Murugaiyah, Vikneswaran

2014-12-01

Novel aromatic embedded Schiff bases have been synthesized in ionic liquid [bmim]Br and evaluated in vitro for their acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes inhibitory activities. Among the newly synthesized compounds, 5f, 5h and 7j displayed higher AChE enzyme inhibitory activities than standard drug, galanthamine, with IC50 values of 1.88, 2.05 and 2.03μM, respectively. Interestingly, all the compounds except for compound 5c displayed higher BChE inhibitories than standard with IC50 values ranging from 3.49 to 19.86μM. Molecular docking analysis for 5f and 7j possessing the most potent AChE and BChE inhibitory activities, disclosed their binding interaction templates to the active site of AChE and BChE enzymes, respectively. Copyright © 2014 Elsevier Inc. All rights reserved.

Novel, customizable scoring functions, parameterized using N-PLS, for structure-based drug discovery.

PubMed

Catana, Cornel; Stouten, Pieter F W

2007-01-01

The ability to accurately predict biological affinity on the basis of in silico docking to a protein target remains a challenging goal in the CADD arena. Typically, "standard" scoring functions have been employed that use the calculated docking result and a set of empirical parameters to calculate a predicted binding affinity. To improve on this, we are exploring novel strategies for rapidly developing and tuning "customized" scoring functions tailored to a specific need. In the present work, three such customized scoring functions were developed using a set of 129 high-resolution protein-ligand crystal structures with measured Ki values. The functions were parametrized using N-PLS (N-way partial least squares), a multivariate technique well-known in the 3D quantitative structure-activity relationship field. A modest correlation between observed and calculated pKi values using a standard scoring function (r2 = 0.5) could be improved to 0.8 when a customized scoring function was applied. To mimic a more realistic scenario, a second scoring function was developed, not based on crystal structures but exclusively on several binding poses generated with the Flo+ docking program. Finally, a validation study was conducted by generating a third scoring function with 99 randomly selected complexes from the 129 as a training set and predicting pKi values for a test set that comprised the remaining 30 complexes. Training and test set r2 values were 0.77 and 0.78, respectively. These results indicate that, even without direct structural information, predictive customized scoring functions can be developed using N-PLS, and this approach holds significant potential as a general procedure for predicting binding affinity on the basis of in silico docking.

Distinguishing Binders from False Positives by Free Energy Calculations: Fragment Screening Against the Flap Site of HIV Protease

PubMed Central

2015-01-01

Molecular docking is a powerful tool used in drug discovery and structural biology for predicting the structures of ligand–receptor complexes. However, the accuracy of docking calculations can be limited by factors such as the neglect of protein reorganization in the scoring function; as a result, ligand screening can produce a high rate of false positive hits. Although absolute binding free energy methods still have difficulty in accurately rank-ordering binders, we believe that they can be fruitfully employed to distinguish binders from nonbinders and reduce the false positive rate. Here we study a set of ligands that dock favorably to a newly discovered, potentially allosteric site on the flap of HIV-1 protease. Fragment binding to this site stabilizes a closed form of protease, which could be exploited for the design of allosteric inhibitors. Twenty-three top-ranked protein–ligand complexes from AutoDock were subject to the free energy screening using two methods, the recently developed binding energy analysis method (BEDAM) and the standard double decoupling method (DDM). Free energy calculations correctly identified most of the false positives (≥83%) and recovered all the confirmed binders. The results show a gap averaging ≥3.7 kcal/mol, separating the binders and the false positives. We present a formula that decomposes the binding free energy into contributions from the receptor conformational macrostates, which provides insights into the roles of different binding modes. Our binding free energy component analysis further suggests that improving the treatment for the desolvation penalty associated with the unfulfilled polar groups could reduce the rate of false positive hits in docking. The current study demonstrates that the combination of docking with free energy methods can be very useful for more accurate ligand screening against valuable drug targets. PMID:25189630

Dynamic Inversion based Control of a Docking Mechanism

NASA Technical Reports Server (NTRS)

Kulkarni, Nilesh V.; Ippolito, Corey; Krishnakumar, Kalmanje

2006-01-01

The problem of position and attitude control of the Stewart platform based docking mechanism is considered motivated by its future application in space missions requiring the autonomous docking capability. The control design is initiated based on the framework of the intelligent flight control architecture being developed at NASA Ames Research Center. In this paper, the baseline position and attitude control system is designed using dynamic inversion with proportional-integral augmentation. The inverse dynamics uses a Newton-Euler formulation that includes the platform dynamics, the dynamics of the individual legs along with viscous friction in the joints. Simulation results are presented using forward dynamics simulated by a commercial physics engine that builds the system as individual elements with appropriate joints and uses constrained numerical integration,

STS-71 Shuttle/Mir mission report

NASA Technical Reports Server (NTRS)

Zimpfer, Douglas J.

1995-01-01

The performance measurements of the space shuttle on-orbit flight control system from the STS-71 mission is presented in this post-flight analysis report. This system is crucial to the stabilization of large space structures and will be needed during the assembly of the International Space Station A mission overview is presented, including the in-orbit flight tests (pre-docking with Mir) and the systems analysis during the docking and undocking operations. Systems errors and lessons learned are discussed, with possible corrective procedures presented for the upcoming Mir flight tests.

Precision in robotic rectal surgery using the da Vinci Xi system and integrated table motion, a technical note.

PubMed

Panteleimonitis, Sofoklis; Harper, Mick; Hall, Stuart; Figueiredo, Nuno; Qureshi, Tahseen; Parvaiz, Amjad

2017-09-15

Robotic rectal surgery is becoming increasingly more popular among colorectal surgeons. However, time spent on robotic platform docking, arm clashing and undocking of the platform during the procedure are factors that surgeons often find cumbersome and time consuming. The newest surgical platform, the da Vinci Xi, coupled with integrated table motion can help to overcome these problems. This technical note aims to describe a standardised operative technique of single docking robotic rectal surgery using the da Vinci Xi system and integrated table motion. A stepwise approach of the da Vinci docking process and surgical technique is described accompanied by an intra-operative video that demonstrates this technique. We also present data collected from a prospectively maintained database. 33 consecutive rectal cancer patients (24 male, 9 female) received robotic rectal surgery with the da Vinci Xi during the preparation of this technical note. 29 (88%) patients had anterior resections, and four (12%) had abdominoperineal excisions. There were no conversions, no anastomotic leaks and no mortality. Median operation time was 331 (249-372) min, blood loss 20 (20-45) mls and length of stay 6.5 (4-8) days. 30-day readmission rate and re-operation rates were 3% (n = 1). This standardised technique of single docking robotic rectal surgery with the da Vinci Xi is safe, feasible and reproducible. The technological advances of the new robotic system facilitate the totally robotic single docking approach.

ARCADE-R2 experiment on board BEXUS 17 stratospheric balloon

NASA Astrophysics Data System (ADS)

Barbetta, Marco; Boesso, Alessandro; Branz, Francesco; Carron, Andrea; Olivieri, Lorenzo; Prendin, Jacopo; Rodeghiero, Gabriele; Sansone, Francesco; Savioli, Livia; Spinello, Fabio; Francesconi, Alessandro

2015-09-01

This paper provides an overview of the ARCADE-R2 experiment, a technology demonstrator that aimed to prove the feasibility of small-scale satellite and/or aircraft systems with automatic (a) attitude determination, (b) control and (c) docking capabilities. The experiment embodies a simplified scenario in which an unmanned vehicle mock-up performs rendezvous and docking operations with a fixed complementary unit. The experiment is composed by a supporting structure, which holds a small vehicle with one translational and one rotational degree of freedom, and its fixed target. The dual system features three main custom subsystems: a relative infrared navigation sensor, an attitude control system based on a reaction wheel and a small-scale docking mechanism. The experiment bus is equipped with pressure and temperature sensors, and wind probes to monitor the external environmental conditions. The experiment flew on board the BEXUS 17 stratospheric balloon on October 10, 2013, where several navigation-control-docking sequences were executed and data on the external pressure, temperature, wind speed and direction were collected, characterizing the atmospheric loads applied to the vehicle. This paper describes the critical components of ARCADE-R2 as well as the main results obtained from the balloon flight.

Fuzzy logic techniques for rendezvous and docking of two geostationary satellites

NASA Technical Reports Server (NTRS)

Ortega, Guillermo

1995-01-01

Large assemblings in space require the ability to manage rendezvous and docking operations. In future these techniques will be required for the gradual build up of big telecommunication platforms in the geostationary orbit. The paper discusses the use of fuzzy logic to model and implement a control system for the docking/berthing of two satellites in geostationary orbit. The system mounted in a chaser vehicle determines the actual state of both satellites and generates torques to execute maneuvers to establish the structural latching. The paper describes the proximity operations to collocate the two satellites in the same orbital window, the fuzzy guidance and navigation of the chaser approaching the target and the final Fuzzy berthing. The fuzzy logic system represents a knowledge based controller that realizes the close loop operations autonomously replacing the conventional control algorithms. The goal is to produce smooth control actions in the proximity of the target and during the docking to avoid disturbance torques in the final assembly orbit. The knowledge of the fuzzy controller consists of a data base of rules and the definitions of the fuzzy sets. The knowledge of an experienced spacecraft controller is captured into a set of rules forming the Rules Data Base.

Import of honeybee prepromelittin into the endoplasmic reticulum: structural basis for independence of SRP and docking protein.

PubMed Central

Müller, G; Zimmermann, R

1987-01-01

Honeybee prepromelittin is correctly processed and imported by dog pancreas microsomes. Insertion of prepromelittin into microsomal membranes, as assayed by signal sequence removal, does not depend on signal recognition particle (SRP) and docking protein. We addressed the question as to how prepromelittin bypasses the SRP/docking protein system. Hybrid proteins between prepromelittin, or carboxy-terminally truncated derivatives, and the cytoplasmic protein dihydrofolate reductase from mouse were constructed. These hybrid proteins were analysed for membrane insertion and sequestration into microsomes. The results suggest the following: (i) The signal sequence of prepromelittin is capable of interacting with the SRP/docking protein system, but this interaction is not mandatory for membrane insertion; this is related to the small size of prepromelittin. (ii) In prepromelittin a cluster of negatively charged amino acids must be balanced by a cluster of positively charged amino acids in order to allow membrane insertion. (iii) In general, a signal sequence can be sufficient to mediate membrane insertion independently of SRP and docking protein in the case of short precursor proteins; however, the presence and distribution of charged amino acids within the mature part of these precursors can play distinct roles. Images Fig. 3. Fig. 4. Fig. 5. Fig. 6. Fig. 7. Fig. 8. Fig. 9. PMID:2820722

Automated Rendezvous and Capture System Development and Simulation for NASA

NASA Technical Reports Server (NTRS)

Roe, Fred D.; Howard, Richard T.; Murphy, Leslie

2004-01-01

The United States does not have an Automated Rendezvous and Capture Docking (AR&C) capability and is reliant on manned control for rendezvous and docking of orbiting spacecraft. T h i s reliance on the labor intensive manned interface for control of rendezvous and docking vehicles has a significant impact on the cost of the operation of the International Space Station (ISS) and precludes the use of any U.S. expendable launch capabilities for Space Station resupply. The Marshall Space Flight Center (MSFC) has conducted pioneering research in the development of an automated rendezvous and capture (or docking) (AR&C) system for U.S. space vehicles. This A M C system was tested extensively using hardware-in-the-loop simulations in the Flight Robotics Laboratory, and a rendezvous sensor, the Video Guidance Sensor was developed and successfully flown on the Space Shuttle on flights STS-87 and STS-95, proving the concept of a video- based sensor. Further developments in sensor technology and vehicle and target configuration have lead to continued improvements and changes in AR&C system development and simulation. A new Advanced Video Guidance Sensor (AVGS) with target will be utilized as the primary navigation sensor on the Demonstration of Autonomous Rendezvous Technologies (DART) flight experiment in 2004. Realtime closed-loop simulations will be performed to validate the improved AR&C systems prior to flight.

36 CFR 13.1122 - Bartlett Cove Public Use Dock.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 36 Parks, Forests, and Public Property 1 2014-07-01 2014-07-01 false Bartlett Cove Public Use Dock. 13.1122 Section 13.1122 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR NATIONAL PARK SYSTEM UNITS IN ALASKA Special Regulations-Glacier Bay National Park and Preserve...

36 CFR 13.1122 - Bartlett Cove Public Use Dock.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 36 Parks, Forests, and Public Property 1 2013-07-01 2013-07-01 false Bartlett Cove Public Use Dock. 13.1122 Section 13.1122 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR NATIONAL PARK SYSTEM UNITS IN ALASKA Special Regulations-Glacier Bay National Park and Preserve...

36 CFR 13.1122 - Bartlett Cove Public Use Dock.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 36 Parks, Forests, and Public Property 1 2010-07-01 2010-07-01 false Bartlett Cove Public Use Dock. 13.1122 Section 13.1122 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR NATIONAL PARK SYSTEM UNITS IN ALASKA Special Regulations-Glacier Bay National Park and Preserve...

36 CFR 13.1122 - Bartlett Cove Public Use Dock.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 36 Parks, Forests, and Public Property 1 2011-07-01 2011-07-01 false Bartlett Cove Public Use Dock. 13.1122 Section 13.1122 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR NATIONAL PARK SYSTEM UNITS IN ALASKA Special Regulations-Glacier Bay National Park and Preserve...

36 CFR 13.1122 - Bartlett Cove Public Use Dock.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 36 Parks, Forests, and Public Property 1 2012-07-01 2012-07-01 false Bartlett Cove Public Use Dock. 13.1122 Section 13.1122 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR NATIONAL PARK SYSTEM UNITS IN ALASKA Special Regulations-Glacier Bay National Park and Preserve...

An integrated autonomous rendezvous and docking system architecture using Centaur modern avionics

NASA Technical Reports Server (NTRS)

Nelson, Kurt

1991-01-01

The avionics system for the Centaur upper stage is in the process of being modernized with the current state-of-the-art in strapdown inertial guidance equipment. This equipment includes an integrated flight control processor with a ring laser gyro based inertial guidance system. This inertial navigation unit (INU) uses two MIL-STD-1750A processors and communicates over the MIL-STD-1553B data bus. Commands are translated into load activation through a Remote Control Unit (RCU) which incorporates the use of solid state relays. Also, a programmable data acquisition system replaces separate multiplexer and signal conditioning units. This modern avionics suite is currently being enhanced through independent research and development programs to provide autonomous rendezvous and docking capability using advanced cruise missile image processing technology and integrated GPS navigational aids. A system concept was developed to combine these technologies in order to achieve a fully autonomous rendezvous, docking, and autoland capability. The current system architecture and the evolution of this architecture using advanced modular avionics concepts being pursued for the National Launch System are discussed.

Evaluation of the novel algorithm of flexible ligand docking with moveable target-protein atoms.

PubMed

Sulimov, Alexey V; Zheltkov, Dmitry A; Oferkin, Igor V; Kutov, Danil C; Katkova, Ekaterina V; Tyrtyshnikov, Eugene E; Sulimov, Vladimir B

2017-01-01

We present the novel docking algorithm based on the Tensor Train decomposition and the TT-Cross global optimization. The algorithm is applied to the docking problem with flexible ligand and moveable protein atoms. The energy of the protein-ligand complex is calculated in the frame of the MMFF94 force field in vacuum. The grid of precalculated energy potentials of probe ligand atoms in the field of the target protein atoms is not used. The energy of the protein-ligand complex for any given configuration is computed directly with the MMFF94 force field without any fitting parameters. The conformation space of the system coordinates is formed by translations and rotations of the ligand as a whole, by the ligand torsions and also by Cartesian coordinates of the selected target protein atoms. Mobility of protein and ligand atoms is taken into account in the docking process simultaneously and equally. The algorithm is realized in the novel parallel docking SOL-P program and results of its performance for a set of 30 protein-ligand complexes are presented. Dependence of the docking positioning accuracy is investigated as a function of parameters of the docking algorithm and the number of protein moveable atoms. It is shown that mobility of the protein atoms improves docking positioning accuracy. The SOL-P program is able to perform docking of a flexible ligand into the active site of the target protein with several dozens of protein moveable atoms: the native crystallized ligand pose is correctly found as the global energy minimum in the search space with 157 dimensions using 4700 CPU ∗ h at the Lomonosov supercomputer.

Currie at RMS controls on the aft flight deck

NASA Image and Video Library

1998-12-05

S88-E-5010 (12-05-98) --- Operating at a control panel on Endeavour's aft flight deck, astronaut Nancy J. Currie works with the robot arm prior to mating the 12.8-ton Unity connecting module to Endeavour's docking system. The mating took place on late afternoon of Dec. 5. A nearby monitor provides a view of the remote manipulator system's (RMS) movements in the cargo bay. The feat marked an important step in assembling the new International Space Station. Manipulating the shuttle's 50-foot-long robot arm, Currie placed Unity just inches above the extended outer ring on Endeavour's docking mechanism, enabling Robert D. Cabana, mission commander to fire downward maneuvering jets, locking the shuttle's docking system to one of two Pressurized Mating Adapters (PMA) attached to Unity. The mating occurred at 5:45 p.m. Central time, as Endeavour sailed over eastern China.

Synthesis of 2-acylated and sulfonated 4-hydroxycoumarins: In vitro urease inhibition and molecular docking studies.

PubMed

Rashid, Umer; Rahim, Fazal; Taha, Muhammad; Arshad, Muhammad; Ullah, Hayat; Mahmood, Tariq; Ali, Muhammad

2016-06-01

Sixteen 4-hydroxycoumarin derivatives were synthesized, characterized through EI-MS and (1)H NMR and screened for urease inhibitory potential. Three compounds exhibited better urease inhibition than the standard inhibitor thiourea (IC50=21±0.11μM) while other four compounds exhibited good to moderate inhibition with IC50 values between 29.45±1.1μM and 69.53±0.9μM. Structure activity relationship was established on the basis of molecular docking studies, which helped to predict the binding interactions of the most active compounds. Copyright © 2016 Elsevier Inc. All rights reserved.

The Advanced Video Guidance Sensor: Orbital Express and the Next Generation

NASA Technical Reports Server (NTRS)

Howard, Richard T.; Heaton, Andrew F.; Pinson, Robin M.; Carrington, Connie L.; Lee, James E.; Bryan, Thomas C.; Robertson, Bryan A.; Spencer, Susan H.; Johnson, Jimmie E.

2008-01-01

The Orbital Express (OE) mission performed the first autonomous rendezvous and docking in the history of the United States on May 5-6, 2007 with the Advanced Video Guidance Sensor (AVGS) acting as one of the primary docking sensors. Since that event, the OE spacecraft performed four more rendezvous and docking maneuvers, each time using the AVGS as one of the docking sensors. The Marshall Space Flight Center's (MSFC's) AVGS is a nearfield proximity operations sensor that was integrated into the Autonomous Rendezvous and Capture Sensor System (ARCSS) on OE. The ARCSS provided the relative state knowledge to allow the OE spacecraft to rendezvous and dock. The AVGS is a mature sensor technology designed to support Automated Rendezvous and Docking (AR&D) operations. It is a video-based laser-illuminated sensor that can determine the relative position and attitude between itself and its target. Due to parts obsolescence, the AVGS that was flown on OE can no longer be manufactured. MSFC has been working on the next generation of AVGS for application to future Constellation missions. This paper provides an overview of the performance of the AVGS on Orbital Express and discusses the work on the Next Generation AVGS (NGAVGS).

Currie at RMS controls on the aft flight deck

NASA Image and Video Library

1998-12-05

S88-E-5030 (12-05-98) --- Astronaut Nancy J. Currie gently mated the 12.8-ton Unity connecting module to Endeavour's docking system late afternoon of Dec. 5, successfully completing the first task in assembling the new International Space Station. Deftly manipulating the shuttle's 50-foot-long robot arm, Currie placed Unity just inches above the extended outer ring on Endeavour's docking mechanism, enabling astronaut Robert D. Cabana, mission commander, to fire downward maneuvering jets, locking the shuttle's docking system to one of two Pressurized Mating Adapters (PMA) attached to Unity. Turning her head to her right, Currie is using one of the TV monitors on the aft flight deck to assist in the precise maneuver. The photo was taken with an electronic still camera (ESC) at 22:31:08 GMT, Dec. 5.

Saturn Apollo Program

NASA Image and Video Library

1974-01-01

This illustration depicts a comparison of two space vehicles, the U.S.'s Saturn IB launch vehicle and the U.S.S.R.'s Soyuz launch vehicle, for the Apollo-Soyuz Test Project. The ASTP was the first international docking of the U.S.'s Apollo spacecraft and the U.S.S.R.'s Soyuz spacecraft in space. A joint engineering team from the two countries met to develop a docking system that permitted the two spacecraft to link in space and allowed the two crews to travel from one spacecraft to the other. This system entailed developing a large habitable Docking Module (DM) to be carried on the Apollo spacecraft to facilitate the joining of two dissimilar spacecraft. The Marshall Space Flight Center was responsible for development and sustaining engineering of the Saturn IB launch vehicle during the mission.

Space tug automatic docking control study. LOCDOK users manual

NASA Technical Reports Server (NTRS)

1974-01-01

A users's manual for the computer programs involved in a study of the space tug docking simulation is presented. The following subjects are considered: (1) subroutine narratives, (2) program elements, (3) system subroutines, and (4) Univac 1108 cross reference listing. The functional and operational requirements for the computer programming are explained.

Investigation of Control System and Display Variations on Spacecraft Handling Qualities for Docking with Stationary and Rotating Targets

NASA Technical Reports Server (NTRS)

Jackson, E. Bruce; Goodrich, Kenneth H.; Bailey, Randall E.; Barnes, James R.; Ragsdale, William A.; Neuhaus, Jason R.

2010-01-01

This paper documents the investigation into the manual docking of a preliminary version of the Crew Exploration Vehicle with stationary and rotating targets in Low Earth Orbit. The investigation was conducted at NASA Langley Research Center in the summer of 2008 in a repurposed fixed-base transport aircraft cockpit and involved nine evaluation astronauts and research pilots. The investigation quantified the benefits of a feed-forward reaction control system thruster mixing scheme to reduce translation-into-rotation coupling, despite unmodeled variations in individual thruster force levels and off-axis center of mass locations up to 12 inches. A reduced rate dead-band in the phase-plane attitude controller also showed some promise. Candidate predictive symbology overlaid on a docking ring centerline camera image did not improve handling qualities, but an innovative attitude status indicator symbol was beneficial. The investigation also showed high workload and handling quality problems when manual dockings were performed with a rotating target. These concerns indicate achieving satisfactory handling quality ratings with a vehicle configuration similar to the nominal Crew Exploration Vehicle may require additional automation.

Applying Pose Clustering and MD Simulations To Eliminate False Positives in Molecular Docking.

PubMed

Makeneni, Spandana; Thieker, David F; Woods, Robert J

2018-03-26

In this work, we developed a computational protocol that employs multiple molecular docking experiments, followed by pose clustering, molecular dynamic simulations (10 ns), and energy rescoring to produce reliable 3D models of antibody-carbohydrate complexes. The protocol was applied to 10 antibody-carbohydrate co-complexes and three unliganded (apo) antibodies. Pose clustering significantly reduced the number of potential poses. For each system, 15 or fewer clusters out of 100 initial poses were generated and chosen for further analysis. Molecular dynamics (MD) simulations allowed the docked poses to either converge or disperse, and rescoring increased the likelihood that the best-ranked pose was an acceptable pose. This approach is amenable to automation and can be a valuable aid in determining the structure of antibody-carbohydrate complexes provided there is no major side chain rearrangement or backbone conformational change in the H3 loop of the CDR regions. Further, the basic protocol of docking a small ligand to a known binding site, clustering the results, and performing MD with a suitable force field is applicable to any protein ligand system.

Enhanced fluorescence norfloxacin substituted naphthalimide derivatives: Molecular docking and antibacterial activity

NASA Astrophysics Data System (ADS)

Kumar, Santosh; Kumar, Gaurav; Tripathi, Amit Kumar; Seena, Sahadevan; Koh, Joonseok

2018-04-01

Hybrid derivatives are a fascinating and challenging process in the area of drug discovery. Naphthalimide derivatives with modified norfloxacin moiety were designed and synthesized. Docking simulations were done to assess the interactions of the derivatives with the E. coli type II topoisomerases Gyrase B and ParE ATP-binding pocket by taking novobiocin as a standard molecule. Results suggested that the norfloxacin substituted naphthalimide derivatives indicate red-shift emission maxima when compared to 4-bromo 1,8-naphthalic anhydride. The molecular docking simulation study revealed that the derivatives have similar interaction but a different mode of binding with the gyrase B ATP-binding pocket as compare to novobiocin. However, they bound to ParE ATP-binding pocket similarly to novobiocin. The antibacterial property was confirmed with disc diffusion method. Our study indicated that the norfloxacin substituted naphthalimide novel derivatives have pronounced fluorescence, anti-topoisomerase activity, and antibacterial properties; therefore, they could be developed into new drug candidates.

Computational Exploration of a Protein Receptor Binding Space with Student Proposed Peptide Ligands

PubMed Central

King, Matthew D.; Phillips, Paul; Turner, Matthew W.; Katz, Michael; Lew, Sarah; Bradburn, Sarah; Andersen, Tim; Mcdougal, Owen M.

2017-01-01

Computational molecular docking is a fast and effective in silico method for the analysis of binding between a protein receptor model and a ligand. The visualization and manipulation of protein to ligand binding in three-dimensional space represents a powerful tool in the biochemistry curriculum to enhance student learning. The DockoMatic tutorial described herein provides a framework by which instructors can guide students through a drug screening exercise. Using receptor models derived from readily available protein crystal structures, docking programs have the ability to predict ligand binding properties, such as preferential binding orientations and binding affinities. The use of computational studies can significantly enhance complimentary wet chemical experimentation by providing insight into the important molecular interactions within the system of interest, as well as guide the design of new candidate ligands based on observed binding motifs and energetics. In this laboratory tutorial, the graphical user interface, DockoMatic, facilitates docking job submissions to the docking engine, AutoDock 4.2. The purpose of this exercise is to successfully dock a 17-amino acid peptide, α-conotoxin TxIA, to the acetylcholine binding protein from Aplysia californica-AChBP to determine the most stable binding configuration. Each student will then propose two specific amino acid substitutions of α-conotoxin TxIA to enhance peptide binding affinity, create the mutant in DockoMatic, and perform docking calculations to compare their results with the class. Students will also compare intermolecular forces, binding energy, and geometric orientation of their prepared analog to their initial α-conotoxin TxIA docking results. PMID:26537635

Space Operations Center System Analysis: Requirements for a Space Operations Center, revision A

NASA Technical Reports Server (NTRS)

Woodcock, G. R.

1982-01-01

The system and program requirements for a space operations center as defined by systems analysis studies are presented as a guide for future study and systems definition. Topics covered include general requirements for safety, maintainability, and reliability, service and habitat modules, the health maintenance facility; logistics modules; the docking tunnel; and subsystem requirements (structures, electrical power, environmental control/life support; extravehicular activity; data management; communications and tracking; docking/berthing; flight control/propulsion; and crew support). Facilities for flight support, construction, satellite and mission servicing, and fluid storage are included as well as general purpose support equipment.

Automatic Docking System Sensor Design, Test, and Mission Performance

NASA Technical Reports Server (NTRS)

Jackson, John L.; Howard, Richard T.; Cole, Helen J.

1998-01-01

The Video Guidance Sensor is a key element of an automatic rendezvous and docking program administered by NASA that was flown on STS-87 in November of 1997. The system used laser illumination of a passive target in the field of view of an on-board camera and processed the video image to determine the relative position and attitude between the target and the sensor. Comparisons of mission results with theoretical models and laboratory measurements will be discussed.

Rendezvous and Docking Strategy for Crewed Segment of the Asteroid Redirect Mission

NASA Technical Reports Server (NTRS)

Hinkel, Heather D.; Cryan, Scott P.; D'Souza, Christopher; Dannemiller, David P.; Brazzel, Jack P.; Condon, Gerald L.; Othon, William L.; Williams, Jacob

2014-01-01

This paper will describe the overall rendezvous, proximity operations and docking (RPOD) strategy in support of the Asteroid Redirect Crewed Mission (ARCM), as part of the Asteroid Redirect Mission (ARM). The focus of the paper is on the crewed mission phase of ARM, starting with the establishment of Orion in the Distant Retrograde Orbit (DRO) and ending with docking to the Asteroid Redirect Vechicle (ARV). The paper will detail the sequence of maneuvers required to execute the rendezvous and proximity operations mission phases along with the on-board navigation strategies, including the final approach phase. The trajectories to be considered will include target vehicles in a DRO. The paper will also discuss the sensor requirements for rendezvous and docking and the various trade studies associated with the final sensor selection. Building on the sensor requirements and trade studies, the paper will include a candidate sensor concept of operations, which will drive the selection of the sensor suite; concurrently, it will be driven by higher level requirements on the system, such as crew timeline constraints and vehicle consummables. This paper will address how many of the seemingly competing requirements will have to be addressed to create a complete system and system design. The objective is to determine a sensor suite and trajectories that enable Orion to successfully rendezvous and dock with a target vehicle in trans lunar space. Finally, the paper will report on the status of a NASA action to look for synergy within RPOD, across the crewed and robotic asteroid missions.

Concurrent-scene/alternate-pattern analysis for robust video-based docking systems

NASA Technical Reports Server (NTRS)

Udomkesmalee, Suraphol

1991-01-01

A typical docking target employs a three-point design of retroreflective tape, one at each endpoint of the center-line, and one on the tip of the central post. Scenes, sensed via laser diode illumination, produce pictures with spots corresponding to desired reflection from the retroreflectors and other reflections. Control corrections for each axis of the vehicle can then be properly applied if the desired spots are accurately tracked. However, initial acquisition of these three spots (detection and identification problem) are non-trivial under a severe noise environment. Signal-to-noise enhancement, accomplished by subtracting the non-illuminated scene from the target scene illuminated by laser diodes, can not eliminate every false spot. Hence, minimization of docking failures due to target mistracking would suggest needed inclusion of added processing features pertaining to target locations. In this paper, we present a concurrent processing scheme for a modified docking target scene which could lead to a perfect docking system. Since the non-illuminated target scene is already available, adding another feature to the three-point design by marking two non-reflective lines, one between the two end-points and one from the tip of the central post to the center-line, would allow this line feature to be picked-up only when capturing the background scene (sensor data without laser illumination). Therefore, instead of performing the image subtraction to generate a picture with a high signal-to-noise ratio, a processed line-image based on the robust line detection technique (Hough transform) can be used to fuse with the actively sensed three-point target image to deduce the true locations of the docking target. This dual-channel confirmation scheme is necessary if a fail-safe system is to be realized from both the sensing and processing point-of-views. Detailed algorithms and preliminary results are presented.

Docking Mechanism on Progress 52

NASA Image and Video Library

2014-02-03

ISS038-E-041175 (3 Feb. 2014) --- This close-up view shows the docking mechanism of the unpiloted Russian ISS Progress 52 resupply ship as it undocks from the International Space Station's Pirs Docking Compartment at 11:21 a.m. (EST) on Feb. 3, 2014. The Progress backed away to a safe distance from the orbital complex to begin several days of tests to study thermal effects of space on its attitude control system. Filled with trash and other unneeded items, the Russian resupply ship will be commanded to re-enter Earth's atmosphere Feb. 11 and disintegrate harmlessly over the Pacific Ocean.

Optoelectronic Sensor System for Guidance in Docking

NASA Technical Reports Server (NTRS)

Howard, Richard T.; Bryan, Thomas C.; Book, Michael L.; Jackson, John L.

2004-01-01

The Video Guidance Sensor (VGS) system is an optoelectronic sensor that provides automated guidance between two vehicles. In the original intended application, the two vehicles would be spacecraft docking together, but the basic principles of design and operation of the sensor are applicable to aircraft, robots, vehicles, or other objects that may be required to be aligned for docking, assembly, resupply, or precise separation. The system includes a sensor head containing a monochrome charge-coupled- device video camera and pulsed laser diodes mounted on the tracking vehicle, and passive reflective targets on the tracked vehicle. The lasers illuminate the targets, and the resulting video images of the targets are digitized. Then, from the positions of the digitized target images and known geometric relationships among the targets, the relative position and orientation of the vehicles are computed. As described thus far, the VGS system is based on the same principles as those of the system described in "Improved Video Sensor System for Guidance in Docking" (MFS-31150), NASA Tech Briefs, Vol. 21, No. 4 (April 1997), page 9a. However, the two systems differ in the details of design and operation. The VGS system is designed to operate with the target completely visible within a relative-azimuth range of +/-10.5deg and a relative-elevation range of +/-8deg. The VGS acquires and tracks the target within that field of view at any distance from 1.0 to 110 m and at any relative roll, pitch, and/or yaw angle within +/-10deg. The VGS produces sets of distance and relative-orientation data at a repetition rate of 5 Hz. The software of this system also accommodates the simultaneous operation of two sensors for redundancy

Robotic fish tracking method based on suboptimal interval Kalman filter

NASA Astrophysics Data System (ADS)

Tong, Xiaohong; Tang, Chao

2017-11-01

Autonomous Underwater Vehicle (AUV) research focused on tracking and positioning, precise guidance and return to dock and other fields. The robotic fish of AUV has become a hot application in intelligent education, civil and military etc. In nonlinear tracking analysis of robotic fish, which was found that the interval Kalman filter algorithm contains all possible filter results, but the range is wide, relatively conservative, and the interval data vector is uncertain before implementation. This paper proposes a ptimization algorithm of suboptimal interval Kalman filter. Suboptimal interval Kalman filter scheme used the interval inverse matrix with its worst inverse instead, is more approximate nonlinear state equation and measurement equation than the standard interval Kalman filter, increases the accuracy of the nominal dynamic system model, improves the speed and precision of tracking system. Monte-Carlo simulation results show that the optimal trajectory of sub optimal interval Kalman filter algorithm is better than that of the interval Kalman filter method and the standard method of the filter.

Correlation of cholinergic drug induced quenching of acetylcholinesterase bound thioflavin-T fluorescence with their inhibition activity

NASA Astrophysics Data System (ADS)

Islam, Mullah Muhaiminul; Rohman, Mostofa Ataur; Gurung, Arun Bahadur; Bhattacharjee, Atanu; Aguan, Kripamoy; Mitra, Sivaprasad

2018-01-01

The development of new acetylcholinesterase inhibitors (AChEIs) and subsequent assay of their inhibition efficiency is considered to be a key step for AD treatment. The fluorescence intensity of thioflavin-T (ThT) bound in the active site of acetylcholinesterase (AChE) quenches substantially in presence of standard AChEI drugs due to the dynamic replacement of the fluorophore from the AChE active site as confirmed from steady state emission as well as time-resolved fluorescence anisotropy measurement and molecular dynamics simulation in conjunction with docking calculation. The parametrized % quenching data for individual system shows excellent correlation with enzyme inhibition activity measured independently by standard Ellman AChE assay method in a high throughput plate reader system. The results are encouraging towards design of a fluorescence intensity based AChE inhibition assay method and may provide a better toolset to rapidly evaluate as well as develop newer AChE-inhibitors for AD treatment.

Using the fast fourier transform in binding free energy calculations.

PubMed

Nguyen, Trung Hai; Zhou, Huan-Xiang; Minh, David D L

2018-04-30

According to implicit ligand theory, the standard binding free energy is an exponential average of the binding potential of mean force (BPMF), an exponential average of the interaction energy between the unbound ligand ensemble and a rigid receptor. Here, we use the fast Fourier transform (FFT) to efficiently evaluate BPMFs by calculating interaction energies when rigid ligand configurations from the unbound ensemble are discretely translated across rigid receptor conformations. Results for standard binding free energies between T4 lysozyme and 141 small organic molecules are in good agreement with previous alchemical calculations based on (1) a flexible complex ( R≈0.9 for 24 systems) and (2) flexible ligand with multiple rigid receptor configurations ( R≈0.8 for 141 systems). While the FFT is routinely used for molecular docking, to our knowledge this is the first time that the algorithm has been used for rigorous binding free energy calculations. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

STS-114 Flight Day 3 Highlights

NASA Technical Reports Server (NTRS)

2005-01-01

Video coverage of Day 3 includes highlights of STS-114 during the approach and docking of Discovery with the International Space Station (ISS). The Return to Flight continues with space shuttle crew members (Commander Eileen Collins, Pilot James Kelly, Mission Specialists Soichi Noguchi, Stephen Robinson, Andrew Thomas, Wendy Lawrence, and Charles Camarda) seen in onboard activities on the fore and aft portions of the flight deck during the orbiter's approach. Camarda sends a greeting to his family, and Collins maneuvers Discovery as the ISS appears steadily closer in sequential still video from the centerline camera of the Orbiter Docking System. The approach includes video of Discovery from the ISS during the orbiter's Rendezvous Pitch Maneuver, giving the ISS a clear view of the thermal protection systems underneath the orbiter. Discovery docks with the Destiny Laboratory of the ISS, and the shuttle crew greets the Expedition 11 crew (Commander Sergei Krikalev and NASA ISS Science Officer and Flight Engineer John Phillips) of the ISS onboard the station. Finally, the Space Station Remote Manipulator System hands the Orbiter Boom Sensor System to its counterpart, the Shuttle Remote Manipulator System.

Molecular Docking and Molecular Dynamics to Identify a Novel Human Immunodeficiency Virus Inhibitor from Alkaloids of Toddalia asiatica

PubMed Central

Priya, R.; Sumitha, Rajendrarao; Doss, C. George Priya; Rajasekaran, C.; Babu, S.; Seenivasan, R.; Siva, R.

2015-01-01

Background: Acquired immunodeficiency syndrome caused by human immunodeficiency virus (HIV) is an immunosuppressive disease. Over the past decades, it has plagued human health due to the grave consequences in its harness. Objective: For this reason, anti-HIV agents are imperative, and the search for the same from natural resources would assure the safety. Materials and Methods: In this investigation we have performed molecular docking, molecular property prediction, drug-likeness score, and molecular dynamics (MD) simulation to develop a novel anti-HIV drug. We have screened 12 alkaloids from a medicinal plant Toddalia asiatica for its probabilistic binding with the active site of the HIV-1-reverse transcriptase (HIV-1-RT) domain (the major contributor to the onset of the disease). Results: The docking results were evaluated based on free energies of binding (ΔG), and the results suggested toddanol, toddanone, and toddalenone to be potent inhibitors of HIV-1-RT. In addition, the alkaloids were subjected to molecular property prediction analysis. Toddanol and toddanone with more rotatable bonds were found to have a drug-likeness score of 0.23 and 0.11, respectively. These scores were comparable with the standard anti-HIV drug zidovudine with a model score 0.28. Finally, two characteristic protein-ligand complexes were exposed to MD simulation to determine the stability of the predicted conformations. Conclusion: The toddanol-RT complex showed higher stability and stronger H-bonds than toddanone-RT complex. Based on these observations, we firmly believe that the alkaloid toddanol could aid in efficient HIV-1 drug discovery. SUMMARY In the present study, the molecular docking and MD simulations are performed to explore the possible binding mode of HIV 1 RT with 12 alkaloids of T. asiatica. Molecular docking by AutoDock4 revealed three alkaloids toddanol, toddanone, and toddalenone with highest binding affinity towards HIV 1 RT. The drug likeness model score revealed a positive score for toddanol and toddanone which is comparable to the drug likeness score of the standard anti HIV drug zidovudine. Results from simulation analysis revealed that toddanol RT complex is more stable than toddanone RT complex inferring toddanol as a potential anti HIV drug molecule. Abbreviations used: HIV: Human immunodeficiency virus, HIV 1 RT: HIV 1 reverse transcriptase, RNase H: Ribonuclease H, MD: Molecular dynamics, PDB: Protein databank, RMSD: Root mean square deviation, RMSF: Root mean square fluctuation. PMID:26929575

Molecular docking studies to map the binding site of squalene synthase inhibitors on dehydrosqualene synthase of Staphylococcus aureus.

PubMed

Kahlon, Amandeep Kaur; Roy, Sudeep; Sharma, Ashok

2010-10-01

Dehydrosqualene synthase of Staphylococcus aureus is involved in the synthesis of golden carotenoid pigment staphyloxanthin. This pigment of S. aureus provides the antioxidant property to this bacterium to survive inside the host cell. Dehydrosqualene synthase (CrtM) is having structural similarity with the human squalene synthase enzyme which is involved in the cholesterol synthesis pathway in humans (Liu et al., 2008). Cholesterol lowering drugs were found to have inhibitory effect on dehydrosqualene synthase enzyme of S. aureus. The present study attempts to focus on squalene synthase inhibitors, lapaquistat acetate and squalestatins reported as cholesterol lowering agents in vitro and in vivo but not studied in context to dehydrosqualene synthase of S. aureus. Mode of binding of lapaquistat acetate and squalestatin analogs on dehydrosqualene synthase (CrtM) enzyme of S. aureus was identified by performing docking analysis with Scigress Explorer Ultra 7.7 docking software. Based on the molecular docking analysis, it was found that the His18, Arg45, Asp48, Asp52, Tyr129, Gln165, Asn168 and Asp172 residues interacted with comparatively high frequency with the inhibitors studied. Comparative docking study with Discovery studio 2.0 also confirmed the involvement of these residues of dehydrosqualene synthase enzyme with the inhibitors studied. This further confirms the importance of these residues in the enzyme function. In silico ADMET analysis was done to predict the ADMET properties of the standard drugs and test compounds. This might provide insights to develop new drugs to target the virulence factor, dehydrosqualene synthase of S. aureus.

Modification of S-Adenosyl-l-Homocysteine as Inhibitor of Nonstructural Protein 5 Methyltransferase Dengue Virus Through Molecular Docking and Molecular Dynamics Simulation

PubMed Central

Tambunan, Usman Sumo Friend; Nasution, Mochammad Arfin Fardiansyah; Azhima, Fauziah; Parikesit, Arli Aditya; Toepak, Erwin Prasetya; Idrus, Syarifuddin; Kerami, Djati

2017-01-01

Dengue fever is still a major threat worldwide, approximately threatening two-fifths of the world’s population in tropical and subtropical countries. Nonstructural protein 5 (NS5) methyltransferase enzyme plays a vital role in the process of messenger RNA capping of dengue by transferring methyl groups from S-adenosyl-l-methionine to N7 atom of the guanine bases of RNA and the RNA ribose group of 2′OH, resulting in S-adenosyl-l-homocysteine (SAH). The modification of SAH compound was screened using molecular docking and molecular dynamics simulation, along with computational ADME-Tox (absorption, distribution, metabolism, excretion, and toxicity) test. The 2 simulations were performed using Molecular Operating Environment (MOE) 2008.10 software, whereas the ADME-Tox test was performed using various software. The modification of SAH compound was done using several functional groups that possess different polarities and properties, resulting in 3460 ligands to be docked. After conducting docking simulation, we earned 3 best ligands (SAH-M331, SAH-M2696, and SAH-M1356) based on ΔGbinding and molecular interactions, which show better results than the standard ligands. Moreover, the results of molecular dynamics simulation show that the best ligands are still able to maintain the active site residue interaction with the binding site until the end of the simulation. After a series of molecular docking and molecular dynamics simulation were performed, we concluded that SAH-M1356 ligand is the most potential SAH-based compound to inhibit NS5 methyltransferase enzyme for treating dengue fever. PMID:28469408

Molecular Docking, Synthesis And Biological Evaluation Of Sulphonylureas/Guanidine Derivatives As Promising Antidiabetics Agent.

PubMed

Panchal, Ishan; Sen, Dhrubo Jyoti; Patel, Ashish D; Shah, Umang; Patel, Mehul; Navle, Archana; Bhavsar, Vashisth

2017-10-02

A series of novel sulphonylureas/guanidine derivatives were designed, synthesized, and evaluated for the treatment of diabetes mellitus. In this study, the designed compounds were docked with AKR1C1 complexes by using glide docking program and docking calculations were performed to predict the binding affinity of the designed compounds with the binding pocket of protein 4YVP and QikProp program was used to predict the ADME/T properties of the analogues. All the targeted derivatives were synthesized and purified by recrystallization. Synthesize compounds were characterized by various physicochemical and various spectroscopic techniques like melting point, thin layer chromatography, infrared spectroscopy (KBr pellets), mass spectroscopy(m/z), 1H NMR (DMSO-d6), and 13C NMR. The synthesized compounds were further studied for biological evolution by alloxan (150 mg/dl, intraperitonial) induced diabetic rat model for in-vivo studies. Among all the synthesized derivatives, 5c and 5d were most potent as per binding energy. Compound 5i have shown a better plasma glucose reduction compared to glibenclamide. Hence, it will further use as a lead compound to develop a more such kind of agent. The docking study revealed that in all designed sulphonylureas/guanidine series of compounds 5c and 5d were found to be most potent compounds as per the binding energy compared to glibenclamide. With the help of details study of in vivo biological activity we observed that compound 5i gives better result compared to glibenclamide as standard. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Improving binding mode and binding affinity predictions of docking by ligand-based search of protein conformations: evaluation in D3R grand challenge 2015

NASA Astrophysics Data System (ADS)

Xu, Xianjin; Yan, Chengfei; Zou, Xiaoqin

2017-08-01

The growing number of protein-ligand complex structures, particularly the structures of proteins co-bound with different ligands, in the Protein Data Bank helps us tackle two major challenges in molecular docking studies: the protein flexibility and the scoring function. Here, we introduced a systematic strategy by using the information embedded in the known protein-ligand complex structures to improve both binding mode and binding affinity predictions. Specifically, a ligand similarity calculation method was employed to search a receptor structure with a bound ligand sharing high similarity with the query ligand for the docking use. The strategy was applied to the two datasets (HSP90 and MAP4K4) in recent D3R Grand Challenge 2015. In addition, for the HSP90 dataset, a system-specific scoring function (ITScore2_hsp90) was generated by recalibrating our statistical potential-based scoring function (ITScore2) using the known protein-ligand complex structures and the statistical mechanics-based iterative method. For the HSP90 dataset, better performances were achieved for both binding mode and binding affinity predictions comparing with the original ITScore2 and with ensemble docking. For the MAP4K4 dataset, although there were only eight known protein-ligand complex structures, our docking strategy achieved a comparable performance with ensemble docking. Our method for receptor conformational selection and iterative method for the development of system-specific statistical potential-based scoring functions can be easily applied to other protein targets that have a number of protein-ligand complex structures available to improve predictions on binding.

Analytical stability and simulation response study for a coupled two-body system

NASA Technical Reports Server (NTRS)

Tao, K. M.; Roberts, J. R.

1975-01-01

An analytical stability study and a digital simulation response study of two connected rigid bodies are documented. Relative rotation of the bodies at the connection is allowed, thereby providing a model suitable for studying system stability and response during a soft-dock regime. Provisions are made of a docking port axes alignment torque and a despin torque capability for encountering spinning payloads. Although the stability analysis is based on linearized equations, the digital simulation is based on nonlinear models.

Shared control on lunar spacecraft teleoperation rendezvous operations with large time delay

NASA Astrophysics Data System (ADS)

Ya-kun, Zhang; Hai-yang, Li; Rui-xue, Huang; Jiang-hui, Liu

2017-08-01

Teleoperation could be used in space on-orbit serving missions, such as object deorbits, spacecraft approaches, and automatic rendezvous and docking back-up systems. Teleoperation rendezvous and docking in lunar orbit may encounter bottlenecks for the inherent time delay in the communication link and the limited measurement accuracy of sensors. Moreover, human intervention is unsuitable in view of the partial communication coverage problem. To solve these problems, a shared control strategy for teleoperation rendezvous and docking is detailed. The control authority in lunar orbital maneuvers that involves two spacecraft as rendezvous and docking in the final phase was discussed in this paper. The predictive display model based on the relative dynamic equations is established to overcome the influence of the large time delay in communication link. We discuss and attempt to prove via consistent, ground-based simulations the relative merits of fully autonomous control mode (i.e., onboard computer-based), fully manual control (i.e., human-driven at the ground station) and shared control mode. The simulation experiments were conducted on the nine-degrees-of-freedom teleoperation rendezvous and docking simulation platform. Simulation results indicated that the shared control methods can overcome the influence of time delay effects. In addition, the docking success probability of shared control method was enhanced compared with automatic and manual modes.

An Experimental Investigation of Leak Rate Performance of a Subscale Candidate Elastomer Docking Space Seal

NASA Technical Reports Server (NTRS)

Garafolo, Nicholas G.; Daniels, Christopher C.

2011-01-01

A novel docking seal was developed for the main interface seal of NASA s Low Impact Docking System (LIDS). This interface seal was designed to maintain acceptable leak rates while being exposed to the harsh environmental conditions of outer space. In this experimental evaluation, a candidate docking seal assembly called Engineering Development Unit (EDU58) was characterized and evaluated against the Constellation Project leak rate requirement. The EDU58 candidate seal assembly was manufactured from silicone elastomer S0383-70 vacuum molded in a metal retainer ring. Four seal designs were considered with unique characteristic heights. The leak rate performance was characterized through a mass point leak rate method by monitoring gas properties within an internal control volume. The leakage performance of the seals were described herein at representative docking temperatures of -50, +23, and +50 C for all four seal designs. Leak performance was also characterized at 100, 74, and 48 percent of full closure. For all conditions considered, the candidate seal assemblies met the Constellation Project leak rate requirement.

Overview of Carbon Dioxide Control Issues During International Space Station/Space Shuttle Joint Docked Operations

NASA Technical Reports Server (NTRS)

Matty, Christopher M.; Hayley, Elizabeth P.

2009-01-01

Manned space vehicles have a common requirement to remove the Carbon Dioxide (CO2) created by the metabolic processes of the crew. The Space Shuttle and International Space Station (ISS) each have systems in place to allow control and removal of CO2 from the habitable cabin environment. During periods where the Space Shuttle is docked to ISS, known as joint docked operations, the Space Shuttle and ISS share a common atmosphere environment. During this period there is an elevated production of CO2 caused by the combined metabolic activity of the Space Shuttle and ISS crew. This elevated CO2 production, combined with the large effective atmosphere created by the collective volumes of the docked vehicles, creates a unique set of requirements for CO2 removal. This paper will describe the individual CO2 control plans implemented by the Space Shuttle and ISS engineering teams, as well as the integrated plans used when both vehicles are docked. In addition, the paper will discuss some of the issues and anomalies experienced by both engineering teams.

A Unified Conformational Selection and Induced Fit Approach to Protein-Peptide Docking

PubMed Central

Trellet, Mikael; Melquiond, Adrien S. J.; Bonvin, Alexandre M. J. J.

2013-01-01

Protein-peptide interactions are vital for the cell. They mediate, inhibit or serve as structural components in nearly 40% of all macromolecular interactions, and are often associated with diseases, making them interesting leads for protein drug design. In recent years, large-scale technologies have enabled exhaustive studies on the peptide recognition preferences for a number of peptide-binding domain families. Yet, the paucity of data regarding their molecular binding mechanisms together with their inherent flexibility makes the structural prediction of protein-peptide interactions very challenging. This leaves flexible docking as one of the few amenable computational techniques to model these complexes. We present here an ensemble, flexible protein-peptide docking protocol that combines conformational selection and induced fit mechanisms. Starting from an ensemble of three peptide conformations (extended, a-helix, polyproline-II), flexible docking with HADDOCK generates 79.4% of high quality models for bound/unbound and 69.4% for unbound/unbound docking when tested against the largest protein-peptide complexes benchmark dataset available to date. Conformational selection at the rigid-body docking stage successfully recovers the most relevant conformation for a given protein-peptide complex and the subsequent flexible refinement further improves the interface by up to 4.5 Å interface RMSD. Cluster-based scoring of the models results in a selection of near-native solutions in the top three for ∼75% of the successfully predicted cases. This unified conformational selection and induced fit approach to protein-peptide docking should open the route to the modeling of challenging systems such as disorder-order transitions taking place upon binding, significantly expanding the applicability limit of biomolecular interaction modeling by docking. PMID:23516555

A unified conformational selection and induced fit approach to protein-peptide docking.

PubMed

Trellet, Mikael; Melquiond, Adrien S J; Bonvin, Alexandre M J J

2013-01-01

Protein-peptide interactions are vital for the cell. They mediate, inhibit or serve as structural components in nearly 40% of all macromolecular interactions, and are often associated with diseases, making them interesting leads for protein drug design. In recent years, large-scale technologies have enabled exhaustive studies on the peptide recognition preferences for a number of peptide-binding domain families. Yet, the paucity of data regarding their molecular binding mechanisms together with their inherent flexibility makes the structural prediction of protein-peptide interactions very challenging. This leaves flexible docking as one of the few amenable computational techniques to model these complexes. We present here an ensemble, flexible protein-peptide docking protocol that combines conformational selection and induced fit mechanisms. Starting from an ensemble of three peptide conformations (extended, a-helix, polyproline-II), flexible docking with HADDOCK generates 79.4% of high quality models for bound/unbound and 69.4% for unbound/unbound docking when tested against the largest protein-peptide complexes benchmark dataset available to date. Conformational selection at the rigid-body docking stage successfully recovers the most relevant conformation for a given protein-peptide complex and the subsequent flexible refinement further improves the interface by up to 4.5 Å interface RMSD. Cluster-based scoring of the models results in a selection of near-native solutions in the top three for ∼75% of the successfully predicted cases. This unified conformational selection and induced fit approach to protein-peptide docking should open the route to the modeling of challenging systems such as disorder-order transitions taking place upon binding, significantly expanding the applicability limit of biomolecular interaction modeling by docking.

Comparing sixteen scoring functions for predicting biological activities of ligands for protein targets.

PubMed

Xu, Weijun; Lucke, Andrew J; Fairlie, David P

2015-04-01

Accurately predicting relative binding affinities and biological potencies for ligands that interact with proteins remains a significant challenge for computational chemists. Most evaluations of docking and scoring algorithms have focused on enhancing ligand affinity for a protein by optimizing docking poses and enrichment factors during virtual screening. However, there is still relatively limited information on the accuracy of commercially available docking and scoring software programs for correctly predicting binding affinities and biological activities of structurally related inhibitors of different enzyme classes. Presented here is a comparative evaluation of eight molecular docking programs (Autodock Vina, Fitted, FlexX, Fred, Glide, GOLD, LibDock, MolDock) using sixteen docking and scoring functions to predict the rank-order activity of different ligand series for six pharmacologically important protein and enzyme targets (Factor Xa, Cdk2 kinase, Aurora A kinase, COX-2, pla2g2a, β Estrogen receptor). Use of Fitted gave an excellent correlation (Pearson 0.86, Spearman 0.91) between predicted and experimental binding only for Cdk2 kinase inhibitors. FlexX and GOLDScore produced good correlations (Pearson>0.6) for hydrophilic targets such as Factor Xa, Cdk2 kinase and Aurora A kinase. By contrast, pla2g2a and COX-2 emerged as difficult targets for scoring functions to predict ligand activities. Although possessing a high hydrophobicity in its binding site, β Estrogen receptor produced reasonable correlations using LibDock (Pearson 0.75, Spearman 0.68). These findings can assist medicinal chemists to better match scoring functions with ligand-target systems for hit-to-lead optimization using computer-aided drug design approaches. Copyright © 2015 Elsevier Inc. All rights reserved.

Computational exploration of a protein receptor binding space with student proposed peptide ligands.

PubMed

King, Matthew D; Phillips, Paul; Turner, Matthew W; Katz, Michael; Lew, Sarah; Bradburn, Sarah; Andersen, Tim; McDougal, Owen M

2016-01-01

Computational molecular docking is a fast and effective in silico method for the analysis of binding between a protein receptor model and a ligand. The visualization and manipulation of protein to ligand binding in three-dimensional space represents a powerful tool in the biochemistry curriculum to enhance student learning. The DockoMatic tutorial described herein provides a framework by which instructors can guide students through a drug screening exercise. Using receptor models derived from readily available protein crystal structures, docking programs have the ability to predict ligand binding properties, such as preferential binding orientations and binding affinities. The use of computational studies can significantly enhance complimentary wet chemical experimentation by providing insight into the important molecular interactions within the system of interest, as well as guide the design of new candidate ligands based on observed binding motifs and energetics. In this laboratory tutorial, the graphical user interface, DockoMatic, facilitates docking job submissions to the docking engine, AutoDock 4.2. The purpose of this exercise is to successfully dock a 17-amino acid peptide, α-conotoxin TxIA, to the acetylcholine binding protein from Aplysia californica-AChBP to determine the most stable binding configuration. Each student will then propose two specific amino acid substitutions of α-conotoxin TxIA to enhance peptide binding affinity, create the mutant in DockoMatic, and perform docking calculations to compare their results with the class. Students will also compare intermolecular forces, binding energy, and geometric orientation of their prepared analog to their initial α-conotoxin TxIA docking results. © 2015 The International Union of Biochemistry and Molecular Biology.

Synthesis, β-glucuronidase inhibition and molecular docking studies of hybrid bisindole-thiosemicarbazides analogs.

PubMed

Taha, Muhammad; Ismail, Nor Hadiani; Imran, Syahrul; Rahim, Fazal; Wadood, Abdul; Khan, Huma; Ullah, Hayat; Salar, Uzma; Khan, Khalid Mohammed

2016-10-01

Hybrid bisindole-thiosemicarbazides analogs (1-18) were synthesized and screened for β-glucuronidase activity. All compounds showed varied degree of β-glucuronidase inhibitory potential when compared with standard d-saccharic acid 1,4-lactone (IC50=48.4±1.25μM). Compounds 4, 7, 9, 6, 5, 12, 17 and 18 showed exceptional β-glucuronidase inhibition with IC50 values ranging from 0.1 to 5.7μM. Compounds 1, 3, 8, 16, 13, 2 and 14 also showed better activities than standard with IC50 values ranging from 7.12 to 15.0μM. The remaining compounds 10, 11, and 15 showed good inhibitory potential with IC50 values 33.2±0.75, 21.4±0.30 and 28.12±0.25μM respectively. Molecular docking studies were carried out to confirm the binding interaction of the compounds. Copyright © 2016 Elsevier Inc. All rights reserved.

Isatin based Schiff bases as inhibitors of α-glucosidase: Synthesis, characterization, in vitro evaluation and molecular docking studies.

PubMed

Rahim, Fazal; Malik, Fazal; Ullah, Hayat; Wadood, Abdul; Khan, Fahad; Javid, Muhammad Tariq; Taha, Muhammad; Rehman, Wajid; Ur Rehman, Ashfaq; Khan, Khalid Mohammed

2015-06-01

Isatin base Schiff bases (1-20) were synthesized, characterized by (1)H NMR and EI/MS and evaluated for α-glucosidase inhibitory potential. Out of these twenty (20) compounds only six analogs showed potent α-glucosidase inhibitory potential with IC50 value ranging in between 2.2±0.25 and 83.5±1.0μM when compared with the standard acarbose (IC50=840±1.73μM). Among the series compound 2 having IC50 value (18.3±0.56μM), 9 (83.5±1.0μM), 11 (3.3±0.25μM), 12 (2.2±0.25μM), 14 (11.8±0.15μM), and 20 (3.0±0.15μM) showed excellent inhibitory potential many fold better than the standard acarbose. The binding interactions of these active analogs were confirmed through molecular docking. Copyright © 2015 Elsevier Inc. All rights reserved.

Gemini rendezvous docking simulator

NASA Image and Video Library

1963-11-04

Multiple exposure of Gemini rendezvous docking simulator. Francis B. Smith wrote in his paper "Simulators for Manned Space Research," "The rendezvous and docking operation of the Gemini spacecraft with the Agena and of the Apollo Command Module with the Lunar Excursion Module have been the subject of simulator studies for several years. [This figure] illustrates the Gemini-Agena rendezvous docking simulator at Langley. The Gemini spacecraft was supported in a gimbal system by an overhead crane and gantry arrangement which provided 6 degrees of freedom - roll, pitch, yaw, and translation in any direction - all controllable by the astronaut in the spacecraft. Here again the controls fed into a computer which in turn provided an input to the servos driving the spacecraft so that it responded to control motions in a manner which accurately simulated the Gemini spacecraft." A.W. Vogeley further described the simulator in his paper "Discussion of Existing and Planned Simulators For Space Research," "Docking operations are considered to start when the pilot first can discern vehicle target size and aspect and terminate, of course, when soft contact is made. ... This facility enables simulation of the docking operation from a distance of 200 feet to actual contact with the target. A full-scale mock-up of the target vehicle is suspended near one end of the track. ... On [the Agena target] we have mounted the actual Agena docking mechanism and also various types of visual aids. We have been able to devise visual aids which have made it possible to accomplish nighttime docking with as much success as daytime docking." -- Published in Barton C. Hacker and James M. Grimwood, On the Shoulders of Titans: A History of Project Gemini, NASA SP-4203; Francis B. Smith, "Simulators for Manned Space Research," Paper presented at the 1966 IEEE International convention, March 21-25, 1966; A.W. Vogeley, "Discussion of Existing and Planned Simulators For Space Research," Paper presented at the Conference on the Role of Simulation in Space Technology, August 17-21, 1964.

On-Orbit Autonomous Assembly from Nanosatellites

NASA Technical Reports Server (NTRS)

Murchison, Luke S.; Martinez, Andres; Petro, Andrew

2015-01-01

The On-Orbit Autonomous Assembly from Nanosatellites (OAAN) project will demonstrate autonomous control algorithms for rendezvous and docking maneuvers; low-power reconfigurable magnetic docking technology; and compact, lightweight and inexpensive precision relative navigation using carrier-phase differential (CD) GPS with a three-degree of freedom ground demonstration. CDGPS is a specific relative position determination method that measures the phase of the GPS carrier wave to yield relative position data accurate to.4 inch (1 centimeter). CDGPS is a technology commonly found in the surveying industry. The development and demonstration of these technologies will fill a current gap in the availability of proven autonomous rendezvous and docking systems for small satellites.

American-built hardware for ASPT undergoes pre-delivery preparations

NASA Image and Video Library

1974-09-11

S74-28295 (September 1974) --- American-built hardware for the joint U.S.-USSR Apollo-Soyuz Test Project mission undergoes pre-delivery preparations in the giant clean room at Rockwell International Corporation?s Space Division at Downey, California. The U.S. portion of the ASTP docking system is in the right foreground. In the right background is the cylindrical-shaped docking module, which is designed to link the Apollo and Soyuz spacecraft when they dock in Earth orbit next summer. In the left background is the Apollo Command Module which they will carry the three American astronauts into Earth orbit. Photo credit: NASA

Space shuttle Atlantis preparing to dock with Mir space station

NASA Image and Video Library

1995-06-28

NM18-309-018 (28 June 1995) --- The Space Shuttle Atlantis orbits Earth at a point above Iraq as photographed by one of the Mir-18 crew members aboard Russia's Mir Space Station. The image was photographed prior to rendezvous and docking of the two spacecraft. The Spacelab science module and the tunnel connecting it to the crew cabin, as well as the added mechanism for interface with the Mir's docking system can be easily seen. The geography pictured is 60 miles northwest of Baghdad. The Buhayrat Ath Tharthar (reservoir) is the widest body of water visible. Also seen are the Tigris and Euphrates Rivers.

Inter-Module Ventilation Changes to the International Space Station Vehicle to Support Integration of the International Docking Adapter and Commercial Crew Vehicles

NASA Technical Reports Server (NTRS)

Link, Dwight E., Jr.; Balistreri, Steven F., Jr.

2015-01-01

The International Space Station (ISS) Environmental Control and Life Support System (ECLSS) is continuing to evolve in the post-Space Shuttle era. The ISS vehicle configuration that is in operation was designed for docking of a Space Shuttle vehicle, and designs currently under development for commercial crew vehicles require different interfaces. The ECLSS Temperature and Humidity Control Subsystem (THC) Inter-Module Ventilation (IMV) must be modified in order to support two docking interfaces at the forward end of ISS, to provide the required air exchange. Development of a new higher-speed IMV fan and extensive ducting modifications are underway to support the new Commercial Crew Vehicle interfaces. This paper will review the new ECLSS IMV development requirements, component design and hardware status, subsystem analysis and testing performed to date, and implementation plan to support Commercial Crew Vehicle docking.

DOT2: Macromolecular Docking With Improved Biophysical Models

PubMed Central

Roberts, Victoria A.; Thompson, Elaine E.; Pique, Michael E.; Perez, Martin S.; Eyck, Lynn Ten

2015-01-01

Computational docking is a useful tool for predicting macromolecular complexes, which are often difficult to determine experimentally. Here we present the DOT2 software suite, an updated version of the DOT intermolecular docking program. DOT2 provides straightforward, automated construction of improved biophysical models based on molecular coordinates, offering checkpoints that guide the user to include critical features. DOT has been updated to run more quickly, allow flexibility in grid size and spacing, and generate a complete list of favorable candidate configu-rations. Output can be filtered by experimental data and rescored by the sum of electrostatic and atomic desolvation energies. We show that this rescoring method improves the ranking of correct complexes for a wide range of macromolecular interactions, and demonstrate that biologically relevant models are essential for biologically relevant results. The flexibility and versatility of DOT2 accommodate realistic models of complex biological systems, improving the likelihood of a successful docking outcome. PMID:23695987

Rigid-Docking Approaches to Explore Protein-Protein Interaction Space.

PubMed

Matsuzaki, Yuri; Uchikoga, Nobuyuki; Ohue, Masahito; Akiyama, Yutaka

Protein-protein interactions play core roles in living cells, especially in the regulatory systems. As information on proteins has rapidly accumulated on publicly available databases, much effort has been made to obtain a better picture of protein-protein interaction networks using protein tertiary structure data. Predicting relevant interacting partners from their tertiary structure is a challenging task and computer science methods have the potential to assist with this. Protein-protein rigid docking has been utilized by several projects, docking-based approaches having the advantages that they can suggest binding poses of predicted binding partners which would help in understanding the interaction mechanisms and that comparing docking results of both non-binders and binders can lead to understanding the specificity of protein-protein interactions from structural viewpoints. In this review we focus on explaining current computational prediction methods to predict pairwise direct protein-protein interactions that form protein complexes.

Molecular docking and simulation studies of gustatory receptor of Aedes aegypti: A potent drug target to distract host-seeking behaviour in mosquitoes.

PubMed

Gupta, Krishna Kant; Sethi, Guneswar; Jayaraman, Manikandan

2016-01-01

It is well reported that exhaled CO 2 and skin odour from human being assist female mosquitoes to locate human host. Basically, the receptors for this activity are expressed in cpA neurons. In both Aedes aegypti and Anopheles gambiae, this CO 2-sensitive olfactory neuron detects myriad number of chemicals present in human skin. Therefore, manipulation of gustatory receptors housing these neurons may serve as important targets for behavioural intervention. The study was aimed towards virtual screening of small molecules in the analyzed conserved active site residues of gustatory receptor and molecular dynamics simulation study of optimum protein-ligand complex to identify a suitable lead molecule for distracting host-seeking behaviour of mosquitoes. The conserved residue analysis of gustatory receptor (GR) of Ae. aegypti and An. gambiae was performed. The structure of GR protein from Ae. aegypti was modeled and validated, and then molecular docking was performed to screen 2903 small molecules against the predicted active residues of GR. Further, simulation studies were also carried out to prove protein-ligand stability. The glutamine 154 residue of GR was found to be highly conserved in Ae. aegypti and An. gambiae. Docking results indicated that the dodecanoic acid, 1,2,3-propanetriyl ester (dynasan 112) was interacting with this residue, as it showed better LibDock score than previously reported ethyl acetate used as mosquito repellant. Simulation studies indicated the structural instability of GR protein in docked form with dynasan 112 suggesting its involvement in structural changes. Based on the interaction energies and stability, this compound has been proposed to be used in mosquitoes' repellant. A novel effective odorant acting as inhibitor of GR is proposed based on its stability, docking score, interactions and RMSD, considering ethyl pyruvate as a standard inhibitor. Host preference and host-seeking ability of mosquito vectors play key roles in disease transmission, a clear understanding of these aspects is essential for preventing the spread of the disease.

Recent progress and future directions in protein-protein docking.

PubMed

Ritchie, David W

2008-02-01

This article gives an overview of recent progress in protein-protein docking and it identifies several directions for future research. Recent results from the CAPRI blind docking experiments show that docking algorithms are steadily improving in both reliability and accuracy. Current docking algorithms employ a range of efficient search and scoring strategies, including e.g. fast Fourier transform correlations, geometric hashing, and Monte Carlo techniques. These approaches can often produce a relatively small list of up to a few thousand orientations, amongst which a near-native binding mode is often observed. However, despite the use of improved scoring functions which typically include models of desolvation, hydrophobicity, and electrostatics, current algorithms still have difficulty in identifying the correct solution from the list of false positives, or decoys. Nonetheless, significant progress is being made through better use of bioinformatics, biochemical, and biophysical information such as e.g. sequence conservation analysis, protein interaction databases, alanine scanning, and NMR residual dipolar coupling restraints to help identify key binding residues. Promising new approaches to incorporate models of protein flexibility during docking are being developed, including the use of molecular dynamics snapshots, rotameric and off-rotamer searches, internal coordinate mechanics, and principal component analysis based techniques. Some investigators now use explicit solvent models in their docking protocols. Many of these approaches can be computationally intensive, although new silicon chip technologies such as programmable graphics processor units are beginning to offer competitive alternatives to conventional high performance computer systems. As cryo-EM techniques improve apace, docking NMR and X-ray protein structures into low resolution EM density maps is helping to bridge the resolution gap between these complementary techniques. The use of symmetry and fragment assembly constraints are also helping to make possible docking-based predictions of large multimeric protein complexes. In the near future, the closer integration of docking algorithms with protein interface prediction software, structural databases, and sequence analysis techniques should help produce better predictions of protein interaction networks and more accurate structural models of the fundamental molecular interactions within the cell.

78 FR 30298 - Alabama Power Company; Notice of Application Accepted for Filing and Soliciting Comments, Motions...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-22

... the eComment system at http://www.ferc.gov/docs-filing/ecomment.asp . You must include your name and..., and three multi-slip boat docks to accommodate 42 watercraft. Approximately 290 feet of riprap and 158... is owned by the permittee and located outside of the project boundary. The proposed boat docks would...

Chemical system biology based molecular interactions to identify inhibitors against Q151M mutant of HIV-1 reverse transcriptase.

PubMed

Pandey, Rajan Kumar; Sharma, Drista; Ojha, Rupal; Bhatt, Tarun Kumar; Prajapati, Vijay Kumar

2018-05-09

The emergence of mutations leading to drug resistance is the main cause of therapeutic failure in the human HIV infection. Chemical system biology approach has drawn great attention to discover new antiretroviral hits with high efficacy and negligible toxicity, which can be used as a prerequisite for HIV drug resistance global action plan 2017-21. To discover potential hits, we docked 49 antiretroviral analogs (n = 6294) against HIV-1 reverse transcriptase Q151M mutant & its wild-type form and narrow downed their number in three sequential modes of docking using Schrödinger suite. Later on, 80 ligands having better docking score than reference ligands (tenofovir and lamivudine) were screened for ADME, toxicity prediction, and binding energy estimation. Simultaneously, the area under the curve (AUC) was estimated using receiver operating characteristics (ROC) curve analysis to validate docking protocols. Finally, single point energy and molecular dynamics simulation approaches were performed for best two ligands (L3 and L14). This study reveals the antiretroviral efficacy of obtained two best ligands and delivers the hits against HIV-1 reverse transcriptase Q151M mutant. Copyright © 2018 Elsevier B.V. All rights reserved.

A open loop guidance architecture for navigationally robust on-orbit docking

NASA Technical Reports Server (NTRS)

Chern, Hung-Sheng

1995-01-01

The development of an open-hop guidance architecture is outlined for autonomous rendezvous and docking (AR&D) missions to determine whether the Global Positioning System (GPS) can be used in place of optical sensors for relative initial position determination of the chase vehicle. Feasible command trajectories for one, two, and three impulse AR&D maneuvers are determined using constrained trajectory optimization. Early AR&D command trajectory results suggest that docking accuracies are most sensitive to vertical position errors at the initial conduction of the chase vehicle. Thus, a feasible command trajectory is based on maximizing the size of the locus of initial vertical positions for which a fixed sequence of impulses will translate the chase vehicle into the target while satisfying docking accuracy requirements. Documented accuracies are used to determine whether relative GPS can achieve the vertical position error requirements of the impulsive command trajectories. Preliminary development of a thruster management system for the Cargo Transfer Vehicle (CTV) based on optimal throttle settings is presented to complete the guidance architecture. Results show that a guidance architecture based on a two impulse maneuvers generated the best performance in terms of initial position error and total velocity change for the chase vehicle.

Initial Investigation of Reaction Control System Design on Spacecraft Handling Qualities for Earth Orbit Docking

NASA Technical Reports Server (NTRS)

Bailey, Randall E.; Jackson, E. Bruce; Goodrich, Kenneth H.; Ragsdale, W. Al; Neuhaus, Jason; Barnes, Jim

2008-01-01

A program of research, development, test, and evaluation is planned for the development of Spacecraft Handling Qualities guidelines. In this first experiment, the effects of Reaction Control System design characteristics and rotational control laws were evaluated during simulated proximity operations and docking. Also, the influence of piloting demands resulting from varying closure rates was assessed. The pilot-in-the-loop simulation results showed that significantly different spacecraft handling qualities result from the design of the Reaction Control System. In particular, cross-coupling between translational and rotational motions significantly affected handling qualities as reflected by Cooper-Harper pilot ratings and pilot workload, as reflected by Task-Load Index ratings. This influence is masked but only slightly by the rotational control system mode. While rotational control augmentation using Rate Command Attitude Hold can reduce the workload (principally, physical workload) created by cross-coupling, the handling qualities are not significantly improved. The attitude and rate deadbands of the RCAH introduced significant mental workload and control compensation to evaluate when deadband firings would occur, assess their impact on docking performance, and apply control inputs to mitigate that impact.

KENNEDY SPACE CENTER, FLA. - The orbiter Ku-band antenna looms large in this view of the Space Shuttle Atlantis' payload bay. Visible just past the antenna system - stowed on the starboard side of the payload bay wall - is the Orbiter Docking System (ODS), and connected to the ODS via a tunnel is the Spacehab Double Module in the aft area of the payload bay. This photograph was taken from the starboard wing platform on the fifth level of the Payload Changeout Room (PCR) at Launch Pad 39A. Work is under way in the PCR to close Atlantis' payload bay doors for flight. Atlantis currently is being targeted for liftoff on Mission STS-79, the fourth docking of the U.S. Shuttle to the Russian Space Station Mir, around Sept. 12.

NASA Image and Video Library

1996-08-22

KENNEDY SPACE CENTER, FLA. - The orbiter Ku-band antenna looms large in this view of the Space Shuttle Atlantis' payload bay. Visible just past the antenna system - stowed on the starboard side of the payload bay wall - is the Orbiter Docking System (ODS), and connected to the ODS via a tunnel is the Spacehab Double Module in the aft area of the payload bay. This photograph was taken from the starboard wing platform on the fifth level of the Payload Changeout Room (PCR) at Launch Pad 39A. Work is under way in the PCR to close Atlantis' payload bay doors for flight. Atlantis currently is being targeted for liftoff on Mission STS-79, the fourth docking of the U.S. Shuttle to the Russian Space Station Mir, around Sept. 12.

Adhesion of Silicone Elastomer Seals for NASA's Crew Exploration Vehicle

NASA Technical Reports Server (NTRS)

deGroh, Henry C., III; Miller, Sharon K. R.; Smith, Ian M.; Daniels, Christopher C.; Steinetz, Bruce M

2008-01-01

Silicone rubber seals are being considered for a number of interfaces on NASA's Crew Exploration Vehicle (CEV). Some of these joints include the docking system, hatches, and heat shield-to-back shell interface. A large diameter molded silicone seal is being developed for the Low Impact Docking System (LIDS) that forms an effective seal between the CEV and International Space Station (ISS) and other future Constellation Program spacecraft. Seals between the heat shield and back shell prevent high temperature reentry gases from leaking into the interface. Silicone rubber seals being considered for these locations have inherent adhesive tendencies that would result in excessive forces required to separate the joints if left unchecked. This paper summarizes adhesion assessments for both as-received and adhesion-mitigated seals for the docking system and the heat shield interface location. Three silicone elastomers were examined: Parker Hannifin S0899-50 and S0383-70 compounds, and Esterline ELA-SA-401 compound. For the docking system application various levels of exposure to atomic oxygen (AO) were evaluated. Moderate AO treatments did not lower the adhesive properties of S0899-50 sufficiently. However, AO pretreatments of approximately 10(exp 20) atoms/sq cm did lower the adhesion of S0383-70 and ELA-SA-401 to acceptable levels. For the heat shield-to-back shell interface application, a fabric covering was also considered. Molding Nomex fabric into the heat shield pressure seal appreciably reduced seal adhesion for the heat shield-to-back shell interface application.

Automated space vehicle control for rendezvous proximity operations

NASA Technical Reports Server (NTRS)

Lea, Robert N.

1988-01-01

Rendezvous during the unmanned space exploration missions, such as a Mars Rover/Sample Return will require a completely automatic system from liftoff to docking. A conceptual design of an automated rendezvous, proximity operations, and docking system is being implemented and validated at the Johnson Space Center (JSC). The emphasis is on the progress of the development and testing of a prototype system for control of the rendezvous vehicle during proximity operations that is currently being developed at JSC. Fuzzy sets are used to model the human capability of common sense reasoning in decision making tasks and such models are integrated with the expert systems and engineering control system technology to create a system that performs comparably to a manned system.

Automated space vehicle control for rendezvous proximity operations

NASA Technical Reports Server (NTRS)

Lea, Robert N.

1988-01-01

Rendezvous during the unmanned space exploration missions, such as a Mars Rover/Sample Return will require a completely automatic system from liftoff to docking. A conceptual design of an automated rendezvous, proximity operations, and docking system is being implemented and validated at the Johnson Space Center (JSC). The emphasis is on the progress of the development and testing of a prototype system for control of the rendezvous vehicle during proximity operations that is currently being developed at JSC. Fuzzy sets are used to model the human capability of common sense reasoning in decision-making tasks and such models are integrated with the expert systems and engineering control system technology to create a system that performs comparably to a manned system.

A python-based docking program utilizing a receptor bound ligand shape: PythDock.

PubMed

Chung, Jae Yoon; Cho, Seung Joo; Hah, Jung-Mi

2011-09-01

PythDock is a heuristic docking program that uses Python programming language with a simple scoring function and a population based search engine. The scoring function considers electrostatic and dispersion/repulsion terms. The search engine utilizes a particle swarm optimization algorithm. A grid potential map is generated using the shape information of a bound ligand within the active site. Therefore, the searching area is more relevant to the ligand binding. To evaluate the docking performance of PythDock, two well-known docking programs (AutoDock and DOCK) were also used with the same data. The accuracy of docked results were measured by the difference of the ligand structure between x-ray structure, and docked pose, i.e., average root mean squared deviation values of the bound ligand were compared for fourteen protein-ligand complexes. Since the number of ligands' rotational flexibility is an important factor affecting the accuracy of a docking, the data set was chosen to have various degrees of flexibility. Although PythDock has a scoring function simpler than those of other programs (AutoDock and DOCK), our results showed that PythDock predicted more accurate poses than both AutoDock4.2 and DOCK6.2. This indicates that PythDock could be a useful tool to study ligand-receptor interactions and could also be beneficial in structure based drug design.

Isolation, characterization and in silico docking studies of synergistic estrogen receptor a anticancer polyphenols from Syzygium alternifolium (Wt.) Walp.

PubMed Central

Yugandhar, Pulicherla; Kumar, Konidala Kranthi; Neeraja, Pabbaraju; Savithramma, Nataru

2017-01-01

Aim: This study aims to isolate, characterize, and in silico evaluate of anticancer polyphenols from different parts of Syzygium alternifolium. Materials and Methods: The polyphenols were isolated by standard protocol and characterized using Fourier-transform infrared (FT-IR), High performance liquid chromatography - Photodiode array detector coupled with Electrospray ionization - mass spectrometry (MS/MS). The compounds were elucidated based on retention time and molecular ions (m/z) either by [M+H]+/[M-H]− with the comparison of standard phenols as well as ReSpect software tool. Furthermore, absorption, distribution, metabolism, and excretion (ADME)/toxicity properties of selected phenolic scaffolds were screened using OSIRIS and SwissADME programs, which incorporate toxicity risk assessments, pharmacokinetics, and rule of five principles. Molecular docking studies were carried out for selected toxicity filtered compounds against breast cancer estrogen receptor a (ERa) structure (protein data bank-ID: 1A52) through AutoDock scoring functions by PyRx virtual screening program. Results: The obtained results showed two intensive peaks in each polyphenol fraction analyzed with FT-IR, confirms O-H/C-O stretch of the phenolic functional group. A total of 40 compounds were obtained, which categorized as 9 different classes. Among them, flavonol group represents more number of polyphenols. In silico studies suggest seven compounds have the possibility to use as future nontoxic inhibitors. Molecular docking studies with ERa revealed the lead molecules unequivocally interact with Leu346, Glu353, Leu391, Arg394, Gly521, Leu525 residues, and Phe404 formed atomic π-stacking with dihydrochromen-4-one ring of ligands as like estrodial, which stabilizes the receptor structure and complicated to generate a single mutation for drug resistance. Conclusion: Overall, these results significantly proposed that isolated phenolics could be served as potential ER mitigators for breast cancer therapy. PMID:28894629

An electromechanical attenuator/actuator for Space Station docking

NASA Technical Reports Server (NTRS)

Stokes, Lebarian; Glenn, Dean; Carroll, Monty B.

1987-01-01

The development of a docking system for aerospace vehicles has identified the need for reusable and variably controlled attenuators/actuators for energy absorption and compliance. One approach to providing both the attenuator and the actuator functions is by way of an electromechanical attenuator/actuator (EMAA) as opposed to a hydraulic system. The use of the electromechanical devices is considered to be more suitable for a space environment because of the absence of contamination from hydraulic fluid leaks and because of the cost effectiveness of maintenance. A smart EMAA that uses range/rate/attitude sensor information to preadjust a docking interface to eliminate misalignments and to minimize contact and stroking forces is described. A prototype EMAA was fabricated and is being tested and evaluated. Results of preliminary testing and analysis already performed have established confidence that this concept is feasible and will provide the desired reliability and low maintenance for repetitive long term operation typical of Space Station requirements.

A Computational Approach to Finding Novel Targets for Existing Drugs

PubMed Central

Li, Yvonne Y.; An, Jianghong; Jones, Steven J. M.

2011-01-01

Repositioning existing drugs for new therapeutic uses is an efficient approach to drug discovery. We have developed a computational drug repositioning pipeline to perform large-scale molecular docking of small molecule drugs against protein drug targets, in order to map the drug-target interaction space and find novel interactions. Our method emphasizes removing false positive interaction predictions using criteria from known interaction docking, consensus scoring, and specificity. In all, our database contains 252 human protein drug targets that we classify as reliable-for-docking as well as 4621 approved and experimental small molecule drugs from DrugBank. These were cross-docked, then filtered through stringent scoring criteria to select top drug-target interactions. In particular, we used MAPK14 and the kinase inhibitor BIM-8 as examples where our stringent thresholds enriched the predicted drug-target interactions with known interactions up to 20 times compared to standard score thresholds. We validated nilotinib as a potent MAPK14 inhibitor in vitro (IC50 40 nM), suggesting a potential use for this drug in treating inflammatory diseases. The published literature indicated experimental evidence for 31 of the top predicted interactions, highlighting the promising nature of our approach. Novel interactions discovered may lead to the drug being repositioned as a therapeutic treatment for its off-target's associated disease, added insight into the drug's mechanism of action, and added insight into the drug's side effects. PMID:21909252

Fast Approximations of the Rotational Diffusion Tensor and their Application to Structural Assembly of Molecular Complexes

PubMed Central

Berlin, Konstantin; O’Leary, Dianne P.; Fushman, David

2011-01-01

We present and evaluate a rigid-body, deterministic, molecular docking method, called ELMDOCK, that relies solely on the three-dimensional structure of the individual components and the overall rotational diffusion tensor of the complex, obtained from nuclear spin-relaxation measurements. We also introduce a docking method, called ELMPATIDOCK, derived from ELMDOCK and based on the new concept of combining the shape-related restraints from rotational diffusion with those from residual dipolar couplings, along with ambiguous contact/interface-related restraints obtained from chemical shift perturbations. ELMDOCK and ELMPATIDOCK use two novel approximations of the molecular rotational diffusion tensor that allow computationally efficient docking. We show that these approximations are accurate enough to properly dock the two components of a complex without the need to recompute the diffusion tensor at each iteration step. We analyze the accuracy, robustness, and efficiency of these methods using synthetic relaxation data for a large variety of protein-protein complexes. We also test our method on three protein systems for which the structure of the complex and experimental relaxation data are available, and analyze the effect of flexible unstructured tails on the outcome of docking. Additionally, we describe a method for integrating the new approximation methods into the existing docking approaches that use the rotational diffusion tensor as a restraint. The results show that the proposed docking method is robust against experimental errors in the relaxation data or structural rearrangements upon complex formation and is computationally more efficient than current methods. The developed approximations are accurate enough to be used in structure refinement protocols. PMID:21604302

Fast approximations of the rotational diffusion tensor and their application to structural assembly of molecular complexes.

PubMed

Berlin, Konstantin; O'Leary, Dianne P; Fushman, David

2011-07-01

We present and evaluate a rigid-body, deterministic, molecular docking method, called ELMDOCK, that relies solely on the three-dimensional structure of the individual components and the overall rotational diffusion tensor of the complex, obtained from nuclear spin-relaxation measurements. We also introduce a docking method, called ELMPATIDOCK, derived from ELMDOCK and based on the new concept of combining the shape-related restraints from rotational diffusion with those from residual dipolar couplings, along with ambiguous contact/interface-related restraints obtained from chemical shift perturbations. ELMDOCK and ELMPATIDOCK use two novel approximations of the molecular rotational diffusion tensor that allow computationally efficient docking. We show that these approximations are accurate enough to properly dock the two components of a complex without the need to recompute the diffusion tensor at each iteration step. We analyze the accuracy, robustness, and efficiency of these methods using synthetic relaxation data for a large variety of protein-protein complexes. We also test our method on three protein systems for which the structure of the complex and experimental relaxation data are available, and analyze the effect of flexible unstructured tails on the outcome of docking. Additionally, we describe a method for integrating the new approximation methods into the existing docking approaches that use the rotational diffusion tensor as a restraint. The results show that the proposed docking method is robust against experimental errors in the relaxation data or structural rearrangements upon complex formation and is computationally more efficient than current methods. The developed approximations are accurate enough to be used in structure refinement protocols. Copyright © 2011 Wiley-Liss, Inc.

SRMS Assisted Docking and Undocking for the Orbiter Repair Maneuver

NASA Technical Reports Server (NTRS)

Quiocho, Leslie J.; Briscoe, Timothy J.; Schliesing, John A.; Braman, Julia M.

2005-01-01

As part of the Orbiter Repair Maneuver (ORM) planned for Return to Flight (RTF) operations, the Shuttle Remote Manipulator System (SRMS) must undock the Orbiter, maneuver it through a complex trajectory at extremely low rates, present it to an EVA crewman at the end of the Space Station Remote Manipulator System to perform the Thermal Protection System (TPS) repair, and then retrace back through the trajectory to dock the Orbiter with the Orbiter Docking System (ODs). The initial and final segments of this operation involve the interaction between the SRMS, ISS, Orbiter and ODs. This paper first provides an overview of the Monte-Carlo screening analysis for the installation (both nominal and contingency), including the variation of separation distance, misalignment conditions, SRMS joint/brake parameter characteristics, and PRCS jet combinations and corresponding thrust durations. The resulting 'optimum' solution is presented based on trade studies between predicted capture success and integrated system loads. This paper then discusses the upgrades to the APAS math model associated with the new SRMS assisted undocking technique and reviews simulation results for various options investigated for either the active and passive separation of the ISS from the Orbiter.

Predicting bioactive conformations and binding modes of macrocycles

NASA Astrophysics Data System (ADS)

Anighoro, Andrew; de la Vega de León, Antonio; Bajorath, Jürgen

2016-10-01

Macrocyclic compounds experience increasing interest in drug discovery. It is often thought that these large and chemically complex molecules provide promising candidates to address difficult targets and interfere with protein-protein interactions. From a computational viewpoint, these molecules are difficult to treat. For example, flexible docking of macrocyclic compounds is hindered by the limited ability of current docking approaches to optimize conformations of extended ring systems for pose prediction. Herein, we report predictions of bioactive conformations of macrocycles using conformational search and binding modes using docking. Conformational ensembles generated using specialized search technique of about 70 % of the tested macrocycles contained accurate bioactive conformations. However, these conformations were difficult to identify on the basis of conformational energies. Moreover, docking calculations with limited ligand flexibility starting from individual low energy conformations rarely yielded highly accurate binding modes. In about 40 % of the test cases, binding modes were approximated with reasonable accuracy. However, when conformational ensembles were subjected to rigid body docking, an increase in meaningful binding mode predictions to more than 50 % of the test cases was observed. Electrostatic effects did not contribute to these predictions in a positive or negative manner. Rather, achieving shape complementarity at macrocycle-target interfaces was a decisive factor. In summary, a combined computational protocol using pre-computed conformational ensembles of macrocycles as a starting point for docking shows promise in modeling binding modes of macrocyclic compounds.

Smart tunnel: Docking mechanism

NASA Technical Reports Server (NTRS)

Schliesing, John A. (Inventor); Edenborough, Kevin L. (Inventor)

1989-01-01

A docking mechanism is presented for the docking of a space vehicle to a space station comprising a flexible tunnel frame structure which is deployable from the space station. The tunnel structure comprises a plurality of series connected frame sections, one end section of which is attached to the space station and the other end attached to a docking module of a configuration adapted for docking in the payload bay of the space vehicle. The docking module is provided with trunnions, adapted for latching engagement with latches installed in the vehicle payload bay and with hatch means connectable to a hatch of the crew cabin of the space vehicle. Each frame section comprises a pair of spaced ring members, interconnected by actuator-attenuator devices which are individually controllable by an automatic control means to impart relative movement of one ring member to the other in six degrees of freedom of motion. The control means includes computer logic responsive to sensor signals of range and attitude information, capture latch condition, structural loads, and actuator stroke for generating commands to the onboard flight control system and the individual actuator-attenuators to deploy the tunnel to effect a coupling with the space vehicle and space station after coupling. A tubular fluid-impervious liner, preferably fabric, is disposed through the frame sections of a size sufficient to accommodate the passage of personnel and cargo.

Dynamic analysis of Apollo-Salyut/Soyuz docking

NASA Technical Reports Server (NTRS)

Schliesing, J. A.

1972-01-01

The use of a docking-system computer program in analyzing the dynamic environment produced by two impacting spacecraft and the attitude control systems is discussed. Performance studies were conducted to determine the mechanism load and capture sensitivity to parametric changes in the initial impact conditions. As indicated by the studies, capture latching is most sensitive to vehicle angular-alinement errors and is least sensitive to lateral-miss error. As proved by load-sensitivity studies, peak loads acting on the Apollo spacecraft are considerably lower than the Apollo design-limit loads.

In Silico Exploration of 1,7-Diazacarbazole Analogs as Checkpoint Kinase 1 Inhibitors by Using 3D QSAR, Molecular Docking Study, and Molecular Dynamics Simulations.

PubMed

Gao, Xiaodong; Han, Liping; Ren, Yujie

2016-05-05

Checkpoint kinase 1 (Chk1) is an important serine/threonine kinase with a self-protection function. The combination of Chk1 inhibitors and anti-cancer drugs can enhance the selectivity of tumor therapy. In this work, a set of 1,7-diazacarbazole analogs were identified as potent Chk1 inhibitors through a series of computer-aided drug design processes, including three-dimensional quantitative structure-activity relationship (3D-QSAR) modeling, molecular docking, and molecular dynamics simulations. The optimal QSAR models showed significant cross-validated correlation q² values (0.531, 0.726), fitted correlation r² coefficients (higher than 0.90), and standard error of prediction (less than 0.250). These results suggested that the developed models possess good predictive ability. Moreover, molecular docking and molecular dynamics simulations were applied to highlight the important interactions between the ligand and the Chk1 receptor protein. This study shows that hydrogen bonding and electrostatic forces are key interactions that confer bioactivity.

Prediction of homoprotein and heteroprotein complexes by protein docking and template‐based modeling: A CASP‐CAPRI experiment

PubMed Central

Velankar, Sameer; Kryshtafovych, Andriy; Huang, Shen‐You; Schneidman‐Duhovny, Dina; Sali, Andrej; Segura, Joan; Fernandez‐Fuentes, Narcis; Viswanath, Shruthi; Elber, Ron; Grudinin, Sergei; Popov, Petr; Neveu, Emilie; Lee, Hasup; Baek, Minkyung; Park, Sangwoo; Heo, Lim; Rie Lee, Gyu; Seok, Chaok; Qin, Sanbo; Zhou, Huan‐Xiang; Ritchie, David W.; Maigret, Bernard; Devignes, Marie‐Dominique; Ghoorah, Anisah; Torchala, Mieczyslaw; Chaleil, Raphaël A.G.; Bates, Paul A.; Ben‐Zeev, Efrat; Eisenstein, Miriam; Negi, Surendra S.; Weng, Zhiping; Vreven, Thom; Pierce, Brian G.; Borrman, Tyler M.; Yu, Jinchao; Ochsenbein, Françoise; Guerois, Raphaël; Vangone, Anna; Rodrigues, João P.G.L.M.; van Zundert, Gydo; Nellen, Mehdi; Xue, Li; Karaca, Ezgi; Melquiond, Adrien S.J.; Visscher, Koen; Kastritis, Panagiotis L.; Bonvin, Alexandre M.J.J.; Xu, Xianjin; Qiu, Liming; Yan, Chengfei; Li, Jilong; Ma, Zhiwei; Cheng, Jianlin; Zou, Xiaoqin; Shen, Yang; Peterson, Lenna X.; Kim, Hyung‐Rae; Roy, Amit; Han, Xusi; Esquivel‐Rodriguez, Juan; Kihara, Daisuke; Yu, Xiaofeng; Bruce, Neil J.; Fuller, Jonathan C.; Wade, Rebecca C.; Anishchenko, Ivan; Kundrotas, Petras J.; Vakser, Ilya A.; Imai, Kenichiro; Yamada, Kazunori; Oda, Toshiyuki; Nakamura, Tsukasa; Tomii, Kentaro; Pallara, Chiara; Romero‐Durana, Miguel; Jiménez‐García, Brian; Moal, Iain H.; Férnandez‐Recio, Juan; Joung, Jong Young; Kim, Jong Yun; Joo, Keehyoung; Lee, Jooyoung; Kozakov, Dima; Vajda, Sandor; Mottarella, Scott; Hall, David R.; Beglov, Dmitri; Mamonov, Artem; Xia, Bing; Bohnuud, Tanggis; Del Carpio, Carlos A.; Ichiishi, Eichiro; Marze, Nicholas; Kuroda, Daisuke; Roy Burman, Shourya S.; Gray, Jeffrey J.; Chermak, Edrisse; Cavallo, Luigi; Oliva, Romina; Tovchigrechko, Andrey

2016-01-01

ABSTRACT We present the results for CAPRI Round 30, the first joint CASP‐CAPRI experiment, which brought together experts from the protein structure prediction and protein–protein docking communities. The Round comprised 25 targets from amongst those submitted for the CASP11 prediction experiment of 2014. The targets included mostly homodimers, a few homotetramers, and two heterodimers, and comprised protein chains that could readily be modeled using templates from the Protein Data Bank. On average 24 CAPRI groups and 7 CASP groups submitted docking predictions for each target, and 12 CAPRI groups per target participated in the CAPRI scoring experiment. In total more than 9500 models were assessed against the 3D structures of the corresponding target complexes. Results show that the prediction of homodimer assemblies by homology modeling techniques and docking calculations is quite successful for targets featuring large enough subunit interfaces to represent stable associations. Targets with ambiguous or inaccurate oligomeric state assignments, often featuring crystal contact‐sized interfaces, represented a confounding factor. For those, a much poorer prediction performance was achieved, while nonetheless often providing helpful clues on the correct oligomeric state of the protein. The prediction performance was very poor for genuine tetrameric targets, where the inaccuracy of the homology‐built subunit models and the smaller pair‐wise interfaces severely limited the ability to derive the correct assembly mode. Our analysis also shows that docking procedures tend to perform better than standard homology modeling techniques and that highly accurate models of the protein components are not always required to identify their association modes with acceptable accuracy. Proteins 2016; 84(Suppl 1):323–348. © 2016 The Authors Proteins: Structure, Function, and Bioinformatics Published by Wiley Periodicals, Inc. PMID:27122118

Enhancing AUV Operational Capabilities: Hovering, Rendezvous, and Docking

DTIC Science & Technology

1997-09-30

ton on the dock that plunges into the bottom of the puck. A rubber sheath insulates the end of the button from the seawater and the exposed current...AUV Navigation and Self -Motion in Shallow Water, ONR. Autonomous Oceanographic Sampling Network Development, ONR. Enhancing AUV Operational...and Failure Recovery, ONR. Dependable Network Topologies with Network Fragment Healing for Component Level Intelli- gent Distributed Control Systems for

ODS alignment ring at soft-dock with ISS

NASA Image and Video Library

2001-08-12

STS105-E-5067 (12 August 2001) --- One of the STS-105 crew members on the aft flight deck of the Space Shuttle Discovery used a digital still camera to record this close-up view of the docking process between the shuttle and the International Space Station (ISS). The shuttle’s Canadarm or Remote Manipulator System (RMS) arm is in its stowed position at right.

New Labour's Policies for Schools: Raising the Standard?

ERIC Educational Resources Information Center

Docking, Jim, Ed.

This book, which is designed primarily for undergraduate and graduate students of education, contains 12 papers devoted the New Labour's policies for schools in the United Kingdom. "Introduction" (Jim Docking) presents an overview of the book's contents and lists questions to help evaluate the effectiveness of New Labour's educational…

I-AUV Docking and Panel Intervention at Sea

PubMed Central

Palomeras, Narcís; Peñalver, Antonio; Massot-Campos, Miquel; Negre, Pep Lluís; Fernández, José Javier; Ridao, Pere; Sanz, Pedro J.; Oliver-Codina, Gabriel

2016-01-01

The use of commercially available autonomous underwater vehicles (AUVs) has increased during the last fifteen years. While they are mainly used for routine survey missions, there is a set of applications that nowadays can be only addressed by manned submersibles or work-class remotely operated vehicles (ROVs) equipped with teleoperated arms: the intervention applications. To allow these heavy vehicles controlled by human operators to perform intervention tasks, underwater structures like observatory facilities, subsea panels or oil-well Christmas trees have been adapted, making them more robust and easier to operate. The TRITON Spanish founded project proposes the use of a light-weight intervention AUV (I-AUV) to carry out intervention applications simplifying the adaptation of these underwater structures and drastically reducing the operational cost. To prove this concept, the Girona 500 I-AUV is used to autonomously dock into an adapted subsea panel and once docked perform an intervention composed of turning a valve and plugging in/unplugging a connector. The techniques used for the autonomous docking and manipulation as well as the design of an adapted subsea panel with a funnel-based docking system are presented in this article together with the results achieved in a water tank and at sea. PMID:27754348

I-AUV Docking and Panel Intervention at Sea.

PubMed

Palomeras, Narcís; Peñalver, Antonio; Massot-Campos, Miquel; Negre, Pep Lluís; Fernández, José Javier; Ridao, Pere; Sanz, Pedro J; Oliver-Codina, Gabriel

2016-10-12

The use of commercially available autonomous underwater vehicles (AUVs) has increased during the last fifteen years. While they are mainly used for routine survey missions, there is a set of applications that nowadays can be only addressed by manned submersibles or work-class remotely operated vehicles (ROVs) equipped with teleoperated arms: the intervention applications. To allow these heavy vehicles controlled by human operators to perform intervention tasks, underwater structures like observatory facilities, subsea panels or oil-well Christmas trees have been adapted, making them more robust and easier to operate. The TRITON Spanish founded project proposes the use of a light-weight intervention AUV (I-AUV) to carry out intervention applications simplifying the adaptation of these underwater structures and drastically reducing the operational cost. To prove this concept, the Girona 500 I-AUV is used to autonomously dock into an adapted subsea panel and once docked perform an intervention composed of turning a valve and plugging in/unplugging a connector. The techniques used for the autonomous docking and manipulation as well as the design of an adapted subsea panel with a funnel-based docking system are presented in this article together with the results achieved in a water tank and at sea.

ATV GNC flight performance and lessons learned

NASA Astrophysics Data System (ADS)

Mongrard, O.; Cavrois, B.; Ankersen, F.; Dubois-Matra, O.; Zink, M.; Vergnol, A.; Piquemal, E.; Pionnier, G.; Southivong, U.

2018-06-01

ESA's fifth and final Automated Transfer Vehicle (ATV), Georges Lemaître, performed its fully automated rendezvous and docking with the International Space Station (ISS) on August 12, 2014. The ATV's navigation sensors have shown their worth docking the 20-ton vehicles with aft port of the Space Station, manoeuvring into position and docking with an excellent accuracy. For the second consecutive time after ATV-4, the accuracy at docking was such that the ATV probe head was directly captured inside the Zvezda docking mechanism without contact with the receiving cone. From 30 km and down to a distance of 250 m, ATV uses GPS (Global Positioning System) information from its own receiver and the Station's that is transmitted over a radiofrequency link. As it moves closer, ATV switches to laser navigation, using the reflection of laser pulses on reflectors mounted on the Space Station. This paper presents the achievements and performance of ATV GNC (Guidance, Navigation, and Control) across the 5 missions for both types of navigation. It will also discuss the observations made during the various flights regarding unforeseen conditions such as space environment or target pattern contamination having a potential impact on performance and how they were resolved.

Homology modeling, active site prediction, and targeting the anti hypertension activity through molecular docking on endothelin – B receptor domain

PubMed Central

Rayalu, Daddam Jayasimha; Selvaraj, Chandrabose; Singh, Sanjeev Kumar; Ganeshan, Ramakrishan; Kumar, Nagapatla Udaya; Seshapani, Panthangi

2012-01-01

In cardiovascular system, activation of Endothelin receptors causes vasoconstriction which leads to Pulmonary Arterial Hypertension (PAH). Endothelin receptor antagonism has emerged as an important therapeutic strategy in pulmonary arterial hypertension. Bosentan is intended to affect vasoconstriction, hypertrophic and fibrotic effects by blocking the actions of receptors ETA and ETB. In this study we identified the action of Bosentan on endothelin B receptor using docking studies with homology modeled endothelin B receptor. Through the modeled protein, the flexible Docking study was performed with Bosentan and its derivatives with theoretically predicted active sites. The results indicated that amino acid ARG82, ARG84 and HIS197 present in endothelin B receptor are core important for binding activities and these residues are having strong hydrogen bond interactions with Bosentan. We have investigated the Bosentan and its derivatives interactions and scoring parameters using gold docking package. Among the docked compounds, one of the Bosentan derivatives BD6 shows better interaction than Bosentan with endothelin B receptor. Our results may be helpful for further investigations in both in vivo and in vitro conditions. PMID:22359440

Protein docking prediction using predicted protein-protein interface.

PubMed

Li, Bin; Kihara, Daisuke

2012-01-10

Many important cellular processes are carried out by protein complexes. To provide physical pictures of interacting proteins, many computational protein-protein prediction methods have been developed in the past. However, it is still difficult to identify the correct docking complex structure within top ranks among alternative conformations. We present a novel protein docking algorithm that utilizes imperfect protein-protein binding interface prediction for guiding protein docking. Since the accuracy of protein binding site prediction varies depending on cases, the challenge is to develop a method which does not deteriorate but improves docking results by using a binding site prediction which may not be 100% accurate. The algorithm, named PI-LZerD (using Predicted Interface with Local 3D Zernike descriptor-based Docking algorithm), is based on a pair wise protein docking prediction algorithm, LZerD, which we have developed earlier. PI-LZerD starts from performing docking prediction using the provided protein-protein binding interface prediction as constraints, which is followed by the second round of docking with updated docking interface information to further improve docking conformation. Benchmark results on bound and unbound cases show that PI-LZerD consistently improves the docking prediction accuracy as compared with docking without using binding site prediction or using the binding site prediction as post-filtering. We have developed PI-LZerD, a pairwise docking algorithm, which uses imperfect protein-protein binding interface prediction to improve docking accuracy. PI-LZerD consistently showed better prediction accuracy over alternative methods in the series of benchmark experiments including docking using actual docking interface site predictions as well as unbound docking cases.

New Standard Weir Design for Dredged Material Management Area, Jacksonville District

DTIC Science & Technology

2014-08-01

dock access, Bartram Island Cell B2, Jacksonville, Florida. Report Documentation Page Form ApprovedOMB No. 0704-0188 Public reporting burden for...Standard Form 298 (Rev. 8-98) Prescribed by ANSI Std Z39-18 ERDC/TN DOTS-14-01 August 2014 2 US Army Corps of Engineers • Engineer Research...and through the riser stack of weir boards. This requires secondary sealing measures in the form of plastic sheeting, geotextiles, and/or burlap

Lessons in molecular recognition. 2. Assessing and improving cross-docking accuracy.

PubMed

Sutherland, Jeffrey J; Nandigam, Ravi K; Erickson, Jon A; Vieth, Michal

2007-01-01

Docking methods are used to predict the manner in which a ligand binds to a protein receptor. Many studies have assessed the success rate of programs in self-docking tests, whereby a ligand is docked into the protein structure from which it was extracted. Cross-docking, or using a protein structure from a complex containing a different ligand, provides a more realistic assessment of a docking program's ability to reproduce X-ray results. In this work, cross-docking was performed with CDocker, Fred, and Rocs using multiple X-ray structures for eight proteins (two kinases, one nuclear hormone receptor, one serine protease, two metalloproteases, and two phosphodiesterases). While average cross-docking accuracy is not encouraging, it is shown that using the protein structure from the complex that contains the bound ligand most similar to the docked ligand increases docking accuracy for all methods ("similarity selection"). Identifying the most successful protein conformer ("best selection") and similarity selection substantially reduce the difference between self-docking and average cross-docking accuracy. We identify universal predictors of docking accuracy (i.e., showing consistent behavior across most protein-method combinations), and show that models for predicting docking accuracy built using these parameters can be used to select the most appropriate docking method.

Docking Offset Between the Space Shuttle and the International Space Station and Resulting Impacts to the Transfer of Attitude Reference and Control

NASA Technical Reports Server (NTRS)

Helms, W. Jason; Pohlkamp, Kara M.

2011-01-01

The Space Shuttle does not dock at an exact 90 degrees to the International Space Station (ISS) x-body axis. This offset from 90 degrees, along with error sources within their respective attitude knowledge, causes the two vehicles to never completely agree on their attitude, even though they operate as a single, mated stack while docked. The docking offset can be measured in flight when both vehicles have good attitude reference and is a critical component in calculations to transfer attitude reference from one vehicle to another. This paper will describe how the docking offset and attitude reference errors between both vehicles are measured and how this information would be used to recover Shuttle attitude reference from ISS in the event of multiple failures. During STS-117, ISS on-board Guidance, Navigation and Control (GNC) computers began having problems and after several continuous restarts, the systems failed. The failure took the ability for ISS to maintain attitude knowledge. This paper will also demonstrate how with knowledge of the docking offset, the contingency procedure to recover Shuttle attitude reference from ISS was reversed in order to provide ISS an attitude reference from Shuttle. Finally, this paper will show how knowledge of the docking offset can be used to speed up attitude control handovers from Shuttle to ISS momentum management. By taking into account the docking offset, Shuttle can be commanded to hold a more precise attitude which better agrees with the ISS commanded attitude such that start up transients with the ISS momentum management controllers are reduced. By reducing start-up transients, attitude control can be transferred from Shuttle to ISS without the use of ISS thrusters saving precious on-board propellant, crew time and minimizing loads placed upon the mated stack.

Development and Control of the Naval Postgraduate School Planar Autonomous Docking Simulator (NPADS)

NASA Astrophysics Data System (ADS)

Porter, Robert D.

2002-09-01

The objective of this thesis was to design, construct and develop the initial autonomous control algorithm for the NPS Planar Autonomous Docking Simulator (NPADS) The effort included hardware design, fabrication, installation and integration; mass property determination; and the development and testing of control laws utilizing MATLAB and Simulink for modeling and LabView for NPADS control, The NPADS vehicle uses air pads and a granite table to simulate a 2-D, drag-free, zero-g space environment, It is a completely self-contained vehicle equipped with eight cold-gas, bang-bang type thrusters and a reaction wheel for motion control, A 'star sensor' CCD camera locates the vehicle on the table while a color CCD docking camera and two robotic arms will locate and dock with a target vehicle, The on-board computer system leverages PXI technology and a single source, simplifying systems integration, The vehicle is powered by two lead-acid batteries for completely autonomous operation, A graphical user interface and wireless Ethernet enable the user to command and monitor the vehicle from a remote command and data acquisition computer. Two control algorithms were developed and allow the user to either control the thrusters and reaction wheel manually or simply specify a desired location and rotation angle,

PharmDock: a pharmacophore-based docking program

PubMed Central

2014-01-01

Background Protein-based pharmacophore models are enriched with the information of potential interactions between ligands and the protein target. We have shown in a previous study that protein-based pharmacophore models can be applied for ligand pose prediction and pose ranking. In this publication, we present a new pharmacophore-based docking program PharmDock that combines pose sampling and ranking based on optimized protein-based pharmacophore models with local optimization using an empirical scoring function. Results Tests of PharmDock on ligand pose prediction, binding affinity estimation, compound ranking and virtual screening yielded comparable or better performance to existing and widely used docking programs. The docking program comes with an easy-to-use GUI within PyMOL. Two features have been incorporated in the program suite that allow for user-defined guidance of the docking process based on previous experimental data. Docking with those features demonstrated superior performance compared to unbiased docking. Conclusion A protein pharmacophore-based docking program, PharmDock, has been made available with a PyMOL plugin. PharmDock and the PyMOL plugin are freely available from http://people.pharmacy.purdue.edu/~mlill/software/pharmdock. PMID:24739488

Inverse simulation system for evaluating handling qualities during rendezvous and docking

NASA Astrophysics Data System (ADS)

Zhou, Wanmeng; Wang, Hua; Thomson, Douglas; Tang, Guojin; Zhang, Fan

2017-08-01

The traditional method used for handling qualities assessment of manned space vehicles is too time-consuming to meet the requirements of an increasingly fast design process. In this study, a rendezvous and docking inverse simulation system to assess the handling qualities of spacecraft is proposed using a previously developed model-predictive-control architecture. By considering the fixed discrete force of the thrusters of the system, the inverse model is constructed using the least squares estimation method with a hyper-ellipsoidal restriction, the continuous control outputs of which are subsequently dispersed by pulse width modulation with sensitivity factors introduced. The inputs in every step are deemed constant parameters, and the method could be considered as a general method for solving nominal, redundant, and insufficient inverse problems. The rendezvous and docking inverse simulation is applied to a nine-degrees-of-freedom platform, and a novel handling qualities evaluation scheme is established according to the operation precision and astronauts' workload. Finally, different nominal trajectories are scored by the inverse simulation and an established evaluation scheme. The scores can offer theoretical guidance for astronaut training and more complex operation missions.

The Drosophila DOCK family protein Sponge is required for development of the air sac primordium

DOE Office of Scientific and Technical Information (OSTI.GOV)

Morishita, Kazushge; Anh Suong, Dang Ngoc; Yoshida, Hideki

Dedicator of cytokinesis (DOCK) family genes are known as DOCK1-DOCK11 in mammals. DOCK family proteins mainly regulate actin filament polymerization and/or depolymerization and are GEF proteins, which contribute to cellular signaling events by activating small G proteins. Sponge (Spg) is a Drosophila counterpart to mammalian DOCK3/DOCK4, and plays a role in embryonic central nervous system development, R7 photoreceptor cell differentiation, and adult thorax development. In order to conduct further functional analyses on Spg in vivo, we examined its localization in third instar larval wing imaginal discs. Immunostaining with purified anti-Spg IgG revealed that Spg mainly localized in the air sacmore » primordium (ASP) in wing imaginal discs. Spg is therefore predicted to play an important role in the ASP. The specific knockdown of Spg by the breathless-GAL4 driver in tracheal cells induced lethality accompanied with a defect in ASP development and the induction of apoptosis. The monitoring of ERK signaling activity in wing imaginal discs by immunostaining with anti-diphospho-ERK IgG revealed reductions in the ERK signal cascade in Spg knockdown clones. Furthermore, the overexpression of D-raf suppressed defects in survival and the proliferation of cells in the ASP induced by the knockdown of Spg. Collectively, these results indicate that Spg plays a critical role in ASP development and tracheal cell viability that is mediated by the ERK signaling pathway. - Highlights: • Spg mainly localizes in the air sac primordium in wing imaginal discs. • Spg plays a critical role in air sac primordium development. • Spg positively regulates the ERK signal cascade.« less

Shipbuilding Docks as Experimental Systems for Realistic Assessments of Anthropogenic Stressors on Marine Organisms

PubMed Central

Harding, Harry R.; Bunce, Tom; Birch, Fiona; Lister, Jessica; Spiga, Ilaria; Benson, Tom; Rossington, Kate; Jones, Diane; Tyler, Charles R.; Simpson, Stephen D.

2017-01-01

Abstract Empirical investigations of the impacts of anthropogenic stressors on marine organisms are typically performed under controlled laboratory conditions, onshore mesocosms, or via offshore experiments with realistic (but uncontrolled) environmental variation. These approaches have merits, but onshore setups are generally small sized and fail to recreate natural stressor fields, whereas offshore studies are often compromised by confounding factors. We suggest the use of flooded shipbuilding docks to allow studying realistic exposure to stressors and their impacts on the intra- and interspecific responses of animals. Shipbuilding docks permit the careful study of groups of known animals, including the evaluation of their behavioral interactions, while enabling full control of the stressor and many environmental conditions. We propose that this approach could be used for assessing the impacts of prominent anthropogenic stressors, including chemicals, ocean warming, and sound. Results from shipbuilding-dock studies could allow improved parameterization of predictive models relating to the environmental risks and population consequences of anthropogenic stressors. PMID:29599545

Multiple Exposure of Rendezvous Docking Simulator - Gemini Program

NASA Image and Video Library

1964-02-07

Multiple exposure of Rendezvous Docking Simulator. Francis B. Smith, described the simulator as follows: The rendezvous and docking operation of the Gemini spacecraft with the Agena and of the Apollo Command Module with the Lunar Excursion Module have been the subject of simulator studies for several years. This figure illustrates the Gemini-Agena rendezvous docking simulator at Langley. The Gemini spacecraft was supported in a gimbal system by an overhead crane and gantry arrangement which provided 6 degrees of freedom - roll, pitch, yaw, and translation in any direction - all controllable by the astronaut in the spacecraft. Here again the controls fed into a computer which in turn provided an input to the servos driving the spacecraft so that it responded to control motions in a manner which accurately simulated the Gemini spacecraft. -- Published in Barton C. Hacker and James M. Grimwood, On the Shoulders of Titans: A History of Project Gemini, NASA SP-4203 Francis B. Smith, Simulators for Manned Space Research, Paper presented at the 1966 IEEE International convention, March 21-25, 1966.

Shipbuilding Docks as Experimental Systems for Realistic Assessments of Anthropogenic Stressors on Marine Organisms.

PubMed

Bruintjes, Rick; Harding, Harry R; Bunce, Tom; Birch, Fiona; Lister, Jessica; Spiga, Ilaria; Benson, Tom; Rossington, Kate; Jones, Diane; Tyler, Charles R; Radford, Andrew N; Simpson, Stephen D

2017-09-01

Empirical investigations of the impacts of anthropogenic stressors on marine organisms are typically performed under controlled laboratory conditions, onshore mesocosms, or via offshore experiments with realistic (but uncontrolled) environmental variation. These approaches have merits, but onshore setups are generally small sized and fail to recreate natural stressor fields, whereas offshore studies are often compromised by confounding factors. We suggest the use of flooded shipbuilding docks to allow studying realistic exposure to stressors and their impacts on the intra- and interspecific responses of animals. Shipbuilding docks permit the careful study of groups of known animals, including the evaluation of their behavioral interactions, while enabling full control of the stressor and many environmental conditions. We propose that this approach could be used for assessing the impacts of prominent anthropogenic stressors, including chemicals, ocean warming, and sound. Results from shipbuilding-dock studies could allow improved parameterization of predictive models relating to the environmental risks and population consequences of anthropogenic stressors.

Neural networks: Alternatives to conventional techniques for automatic docking

NASA Technical Reports Server (NTRS)

Vinz, Bradley L.

1994-01-01

Automatic docking of orbiting spacecraft is a crucial operation involving the identification of vehicle orientation as well as complex approach dynamics. The chaser spacecraft must be able to recognize the target spacecraft within a scene and achieve accurate closing maneuvers. In a video-based system, a target scene must be captured and transformed into a pattern of pixels. Successful recognition lies in the interpretation of this pattern. Due to their powerful pattern recognition capabilities, artificial neural networks offer a potential role in interpretation and automatic docking processes. Neural networks can reduce the computational time required by existing image processing and control software. In addition, neural networks are capable of recognizing and adapting to changes in their dynamic environment, enabling enhanced performance, redundancy, and fault tolerance. Most neural networks are robust to failure, capable of continued operation with a slight degradation in performance after minor failures. This paper discusses the particular automatic docking tasks neural networks can perform as viable alternatives to conventional techniques.

InterEvDock2: an expanded server for protein docking using evolutionary and biological information from homology models and multimeric inputs.

PubMed

Quignot, Chloé; Rey, Julien; Yu, Jinchao; Tufféry, Pierre; Guerois, Raphaël; Andreani, Jessica

2018-05-08

Computational protein docking is a powerful strategy to predict structures of protein-protein interactions and provides crucial insights for the functional characterization of macromolecular cross-talks. We previously developed InterEvDock, a server for ab initio protein docking based on rigid-body sampling followed by consensus scoring using physics-based and statistical potentials, including the InterEvScore function specifically developed to incorporate co-evolutionary information in docking. InterEvDock2 is a major evolution of InterEvDock which allows users to submit input sequences - not only structures - and multimeric inputs and to specify constraints for the pairwise docking process based on previous knowledge about the interaction. For this purpose, we added modules in InterEvDock2 for automatic template search and comparative modeling of the input proteins. The InterEvDock2 pipeline was benchmarked on 812 complexes for which unbound homology models of the two partners and co-evolutionary information are available in the PPI4DOCK database. InterEvDock2 identified a correct model among the top 10 consensus in 29% of these cases (compared to 15-24% for individual scoring functions) and at least one correct interface residue among 10 predicted in 91% of these cases. InterEvDock2 is thus a unique protein docking server, designed to be useful for the experimental biology community. The InterEvDock2 web interface is available at http://bioserv.rpbs.univ-paris-diderot.fr/services/InterEvDock2/.

Image dissector camera system study

NASA Technical Reports Server (NTRS)

Howell, L.

1984-01-01

Various aspects of a rendezvous and docking system using an image dissector detector as compared to a GaAs detector were discussed. Investigation into a gimbled scanning system is also covered and the measured video response curves from the image dissector camera are presented. Rendezvous will occur at ranges greater than 100 meters. The maximum range considered was 1000 meters. During docking, the range, range-rate, angle, and angle-rate to each reflector on the satellite must be measured. Docking range will be from 3 to 100 meters. The system consists of a CW laser diode transmitter and an image dissector receiver. The transmitter beam is amplitude modulated with three sine wave tones for ranging. The beam is coaxially combined with the receiver beam. Mechanical deflection of the transmitter beam, + or - 10 degrees in both X and Y, can be accomplished before or after it is combined with the receiver beam. The receiver will have a field-of-view (FOV) of 20 degrees and an instantaneous field-of-view (IFOV) of two milliradians (mrad) and will be electronically scanned in the image dissector. The increase in performance obtained from the GaAs photocathode is not needed to meet the present performance requirements.

Imaging Flash Lidar for Safe Landing on Solar System Bodies and Spacecraft Rendezvous and Docking

NASA Technical Reports Server (NTRS)

Amzajerdian, Farzin; Roback, Vincent E.; Bulyshev, Alexander E.; Brewster, Paul F.; Carrion, William A; Pierrottet, Diego F.; Hines, Glenn D.; Petway, Larry B.; Barnes, Bruce W.; Noe, Anna M.

2015-01-01

NASA has been pursuing flash lidar technology for autonomous, safe landing on solar system bodies and for automated rendezvous and docking. During the final stages of the landing from about 1 kilometer to 500 meters above the ground, the flash lidar can generate 3-Dimensional images of the terrain to identify hazardous features such as craters, rocks, and steep slopes. The onboard flight computer can then use the 3-D map of terrain to guide the vehicle to a safe location. As an automated rendezvous and docking sensor, the flash lidar can provide relative range, velocity, and bearing from an approaching spacecraft to another spacecraft or a space station. NASA Langley Research Center has developed and demonstrated a flash lidar sensor system capable of generating 16,000 pixels range images with 7 centimeters precision, at 20 Hertz frame rate, from a maximum slant range of 1800 m from the target area. This paper describes the lidar instrument and presents the results of recent flight tests onboard a rocket-propelled free-flyer vehicle (Morpheus) built by NASA Johnson Space Center. The flights were conducted at a simulated lunar terrain site, consisting of realistic hazard features and designated landing areas, built at NASA Kennedy Space Center specifically for this demonstration test. This paper also provides an overview of the plan for continued advancement of the flash lidar technology aimed at enhancing its performance to meet both landing and automated rendezvous and docking applications.

A relative navigation sensor for CubeSats based on LED fiducial markers

NASA Astrophysics Data System (ADS)

Sansone, Francesco; Branz, Francesco; Francesconi, Alessandro

2018-05-01

Small satellite platforms are becoming very appealing both for scientific and commercial applications, thanks to their low cost, short development times and availability of standard components and subsystems. The main disadvantage with such vehicles is the limitation of available resources to perform mission tasks. To overcome this drawback, mission concepts are under study that foresee cooperation between autonomous small satellites to accomplish complex tasks; among these, on-orbit servicing and on-orbit assembly of large structures are of particular interest and the global scientific community is putting a significant effort in the miniaturization of critical technologies that are required for such innovative mission scenarios. In this work, the development and the laboratory testing of an accurate relative navigation package for nanosatellites compliant to the CubeSat standard is presented. The system features a small camera and two sets of LED fiducial markers, and is conceived as a standard package that allows small spacecraft to perform mutual tracking during rendezvous and docking maneuvers. The hardware is based on off-the-shelf components assembled in a compact configuration that is compatible with the CubeSat standard. The image processing and pose estimation software was custom developed. The experimental evaluation of the system allowed to determine both the static and dynamic performances. The system is capable to determine the close range relative position and attitude faster than 10 S/s, with errors always below 10 mm and 2 deg.

77 FR 23480 - Massachusetts Marine Sanitation Device Standard-Receipt of Petition

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-19

.... S. Environmental Protection Agency, that adequate facilities for the safe and sanitary removal and... amended by Public Law 95-217 and Public Law 100-4, that adequate facilities for the safe and sanitary... and dock space for the recreational and commercial vessels. Mount Hope Bay is a shared waterbody...

Synthesis of bis-indolylmethanes as new potential inhibitors of β-glucuronidase and their molecular docking studies.

PubMed

Taha, Muhammad; Ullah, Hayat; Al Muqarrabun, Laode Muhammad Ramadhan; Khan, Muhammad Naseem; Rahim, Fazal; Ahmat, Norizan; Ali, Muhammad; Perveen, Shahnaz

2018-01-01

Thirty-two (32) bis-indolylmethane-hydrazone hybrids 1-32 were synthesized and characterized by 1 HNMR, 13 CNNMR and HREI-MS. All compounds were evaluated in vitro for β-glucuronidase inhibitory potential. All analogs showed varying degree of β-glucuronidase inhibitory potential ranging from 0.10 ± 0.01 to 48.50 ± 1.10 μM when compared with the standard drug d-saccharic acid-1,4-lactone (IC 50 value 48.30 ± 1.20 μM). Derivatives 1-32 showed the highest β-glucuronidase inhibitory potentials which is many folds better than the standard drug d-saccharic acid-1,4-lactone. Further molecular docking study validated the experimental results. It was proposed that bis-indolylmethane may interact with some amino acid residues located within the active site of β-glucuronidase enzyme. This study has culminated in the identification of a new class of potent β-glucuronidase inhibitors. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

EMI from Spacecraft Docking Systems Spacecraft Charging - Plasma Contact Potentials

NASA Technical Reports Server (NTRS)

Norgard, John D.; Scully, Robert; Musselman, Randall

2012-01-01

The plasma contact potential of a visiting vehicle (VV), such as the Orion Service Module (SM), is determined while docking at the Orion Crew Exploration Vehicle (CEV). Due to spacecraft charging effects on-orbit, the potential difference between the CEV and the VV can be large at docking, and an electrostatic discharge (ESD) could occur at capture, which could degrade, disrupt, damage, or destroy sensitive electronic equipment on the CEV and/or VV. Analytical and numerical models of the CEV are simulated to predict the worst-case potential difference between the CEV and the VV when the CEV is unbiased (solar panels unlit: eclipsed in the dark and inactive) or biased (solar panels sunlit: in the light and active).

Hydra Rendezvous and Docking Sensor

NASA Technical Reports Server (NTRS)

Roe, Fred; Carrington, Connie

2007-01-01

The U.S. technology to support a CEV AR&D activity is mature and was developed by NASA and supporting industry during an extensive research and development program conducted during the 1990's and early 2000 time frame at the Marshall Space Flight Center. Development and demonstration of a rendezvous/docking sensor was identified early in the AR&D Program as the critical enabling technology that allows automated proxinity operations and docking. A first generation rendezvous/docking sensor, the Video Guidance Sensor (VGS) was developed and successfully flown on STS 87 and again on STS 95, proving the concept of a video-based sensor. Advances in both video and signal processing technologies and the lessons learned from the two successful flight experiments provided a baseline for the development of a new generation of video based rendezvous/docking sensor. The Advanced Video Guidance Sensor (AVGS) has greatly increased performance and additional capability for longer-range operation. A Demonstration Automatic Rendezvous Technology (DART) flight experiment was flown in April 2005 using AVGS as the primary proximity operations sensor. Because of the absence of a docking mechanism on the target satellite, this mission did not demonstrate the ability of the sensor to coltrold ocking. Mission results indicate that the rendezvous sensor operated successfully in "spot mode" (2 km acquisition of the target, bearing data only) but was never commanded to "acquire and track" the docking target. Parts obsolescence issues prevent the construction of current design AVGS units to support the NASA Exploration initiative. This flight proven AR&D technology is being modularized and upgraded with additional capabilities through the Hydra project at the Marshall Space Flight Center. Hydra brings a unique engineering approach and sensor architecture to the table, to solve the continuing issues of parts obsolescence and multiple sensor integration. This paper presents an approach to sensor hardware trades, to address the needs of future vehicles that may rendezvous and dock with the International Space Station (ISS). It will also discuss approaches for upgrading AVGS to address parts obsolescence, and concepts for modularizing the sensor to provide configuration flexibility for multiple vehicle applications. Options for complementary sensors to be integrated into the multi-head Hydra system will also be presented. Complementary sensor options include ULTOR, a digital image correlator system that could provide relative six-degree-of-freedom information independently from AVGS, and time-of-flight sensors, which determine the range between vehicles by timing pulses that travel from the sensor to the target and back. Common targets and integrated targets, suitable for use with the multi-sensor options in Hydra, will also be addressed.

Comparative molecular field analysis and molecular docking studies on novel aryl chalcone derivatives against an important drug target cysteine protease in Plasmodium falciparum.

PubMed

Thillainayagam, Mahalakshmi; Anbarasu, Anand; Ramaiah, Sudha

2016-08-21

The computational studies namely molecular docking simulations and Comparative Molecular Field Analysis (CoMFA) are executed on series of 52 novel aryl chalcones derivatives using Plasmodium falciparum cysteine proteases (falcipain - 2) as vital target. In the present study, the correlation between different molecular field effects namely steric and electrostatic interactions and chemical structures to the inhibitory activities of novel aryl chalcone derivatives is inferred to perceive the major structural prerequisites for the rational design and development of potent and novel lead anti-malarial compound. The apparent binding conformations of all the compounds at the active site of falcipain - 2 and the hydrogen-bond interactions which could be used to modify the inhibitory activities are identified by using Surflex-dock study. Statistically significant CoMFA model has been developed with the cross-validated correlation coefficient (q(2)) of 0.912 and the non-cross-validated correlation coefficient (r(2)) of 0.901. Standard error of estimation (SEE) of 0.210, with the optimum number of components is ten. The predictability of the derived model is examined with a test set consists of sixteen compounds and the predicted r(2) value is found to be 0.924. The docking and QSAR study results confer crucial suggestions for the optimization of novel 1,3-diphenyl-2-propen-1-one derivatives and synthesis of effective anti- malarial compounds. Copyright © 2016 Elsevier Ltd. All rights reserved.

Synthesis, docking and ADMET studies of novel chalcone triazoles for anti-cancer and anti-diabetic activity.

PubMed

Chinthala, Yakaiah; Thakur, Sneha; Tirunagari, Shalini; Chinde, Srinivas; Domatti, Anand Kumar; Arigari, Niranjana Kumar; K V N S, Srinivas; Alam, Sarfaraz; Jonnala, Kotesh Kumar; Khan, Feroz; Tiwari, Ashok; Grover, Paramjit

2015-03-26

A series of novel chalcone-triazole derivatives were synthesized and screened for in vitro anticancer activity on the human cancer cell lines IMR32 (neuroblastoma), HepG2 (hepatoma) and MCF-7 (breast adenocarcinoma), DU-145 (prostate carcinoma), and A549 (lung adenocarcinoma). Among the tested compounds, 4r showed the most promising anticancer activity in all the cell lines whereas, compounds 4c (IC50 65.86 μM), 4e (IC50 66.28 μM), 4o (IC50 35.81 μM), 4q (IC50 50.82 μM) and 4s (IC50 48.63 μM) showed better activity than the standard doxorubicin (IC50 69.33 μM) in A549 cell line alone. Rat intestinal α-glucosidase inhibitory activity of the synthesized derivatives showed 4m (IC50 67.77 μM), 4p (IC50 74.94 in μM) and 4s (IC50 102.10 μM) as most active compared to others. The in silico docking of synthesized derivatives 4a-4t with DNA topoisomerase IIα revealed the LibDock score in the range of 71.2623-118.29 whereas, compounds 4h, 4m, 4p and 4s with docking target α-glucosidase were in the range of 100.372-107.784. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Identification of potential herbal inhibitor of acetylcholinesterase associated Alzheimer's disorders using molecular docking and molecular dynamics simulation.

PubMed

Seniya, Chandrabhan; Khan, Ghulam Jilani; Uchadia, Kuldeep

2014-01-01

Cholinesterase inhibitors (ChE-Is) are the standard for the therapy of AD associated disorders and are the only class of approved drugs by the Food and Drug Administration (FDA). Additionally, acetylcholinesterase (AChE) is the target for many Alzheimer's dementia drugs which block the function of AChE but have some side effects. Therefore, in this paper, an attempt was made to elucidate cholinesterase inhibition potential of secondary metabolite from Cannabis plant which has negligible or no side effect. Molecular docking of 500 herbal compounds, against AChE, was performed using Autodock 4.2 as per the standard protocols. Molecular dynamics simulations have also been carried out to check stability of binding complex in water for 1000 ps. Our molecular docking and simulation have predicted high binding affinity of secondary metabolite (C28H34N2O6) to AChE. Further, molecular dynamics simulations for 1000 ps suggest that ligand interaction with the residues Asp72, Tyr70-121-334, and Phe288 of AChE, all of which fall under active site/subsite or binding pocket, might be critical for the inhibitory activity of AChE. This approach might be helpful to understand the selectivity of the given drug molecule in the treatment of Alzheimer's disease. The study provides evidence for consideration of C28H34N2O6 as a valuable small ligand molecule in treatment and prevention of AD associated disorders and further in vitro and in vivo investigations may prove its therapeutic potential.

Identification of Potential Herbal Inhibitor of Acetylcholinesterase Associated Alzheimer's Disorders Using Molecular Docking and Molecular Dynamics Simulation

PubMed Central

Seniya, Chandrabhan; Khan, Ghulam Jilani; Uchadia, Kuldeep

2014-01-01

Cholinesterase inhibitors (ChE-Is) are the standard for the therapy of AD associated disorders and are the only class of approved drugs by the Food and Drug Administration (FDA). Additionally, acetylcholinesterase (AChE) is the target for many Alzheimer's dementia drugs which block the function of AChE but have some side effects. Therefore, in this paper, an attempt was made to elucidate cholinesterase inhibition potential of secondary metabolite from Cannabis plant which has negligible or no side effect. Molecular docking of 500 herbal compounds, against AChE, was performed using Autodock 4.2 as per the standard protocols. Molecular dynamics simulations have also been carried out to check stability of binding complex in water for 1000 ps. Our molecular docking and simulation have predicted high binding affinity of secondary metabolite (C28H34N2O6) to AChE. Further, molecular dynamics simulations for 1000 ps suggest that ligand interaction with the residues Asp72, Tyr70-121-334, and Phe288 of AChE, all of which fall under active site/subsite or binding pocket, might be critical for the inhibitory activity of AChE. This approach might be helpful to understand the selectivity of the given drug molecule in the treatment of Alzheimer's disease. The study provides evidence for consideration of C28H34N2O6 as a valuable small ligand molecule in treatment and prevention of AD associated disorders and further in vitro and in vivo investigations may prove its therapeutic potential. PMID:25054066

F2Dock: Fast Fourier Protein-Protein Docking

PubMed Central

Bajaj, Chandrajit; Chowdhury, Rezaul; Siddavanahalli, Vinay

2009-01-01

The functions of proteins is often realized through their mutual interactions. Determining a relative transformation for a pair of proteins and their conformations which form a stable complex, reproducible in nature, is known as docking. It is an important step in drug design, structure determination and understanding function and structure relationships. In this paper we extend our non-uniform fast Fourier transform docking algorithm to include an adaptive search phase (both translational and rotational) and thereby speed up its execution. We have also implemented a multithreaded version of the adaptive docking algorithm for even faster execution on multicore machines. We call this protein-protein docking code F2Dock (F2 = Fast Fourier). We have calibrated F2Dock based on an extensive experimental study on a list of benchmark complexes and conclude that F2Dock works very well in practice. Though all docking results reported in this paper use shape complementarity and Coulombic potential based scores only, F2Dock is structured to incorporate Lennard-Jones potential and re-ranking docking solutions based on desolvation energy. PMID:21071796

Ligand-biased ensemble receptor docking (LigBEnD): a hybrid ligand/receptor structure-based approach

NASA Astrophysics Data System (ADS)

Lam, Polo C.-H.; Abagyan, Ruben; Totrov, Maxim

2018-01-01

Ligand docking to flexible protein molecules can be efficiently carried out through ensemble docking to multiple protein conformations, either from experimental X-ray structures or from in silico simulations. The success of ensemble docking often requires the careful selection of complementary protein conformations, through docking and scoring of known co-crystallized ligands. False positives, in which a ligand in a wrong pose achieves a better docking score than that of native pose, arise as additional protein conformations are added. In the current study, we developed a new ligand-biased ensemble receptor docking method and composite scoring function which combine the use of ligand-based atomic property field (APF) method with receptor structure-based docking. This method helps us to correctly dock 30 out of 36 ligands presented by the D3R docking challenge. For the six mis-docked ligands, the cognate receptor structures prove to be too different from the 40 available experimental Pocketome conformations used for docking and could be identified only by receptor sampling beyond experimentally explored conformational subspace.

Molecular docking.

PubMed

Morris, Garrett M; Lim-Wilby, Marguerita

2008-01-01

Molecular docking is a key tool in structural molecular biology and computer-assisted drug design. The goal of ligand-protein docking is to predict the predominant binding mode(s) of a ligand with a protein of known three-dimensional structure. Successful docking methods search high-dimensional spaces effectively and use a scoring function that correctly ranks candidate dockings. Docking can be used to perform virtual screening on large libraries of compounds, rank the results, and propose structural hypotheses of how the ligands inhibit the target, which is invaluable in lead optimization. The setting up of the input structures for the docking is just as important as the docking itself, and analyzing the results of stochastic search methods can sometimes be unclear. This chapter discusses the background and theory of molecular docking software, and covers the usage of some of the most-cited docking software.

α-Cyclodextrin dimer complexes of dopamine and levodopa derivatives to assess drug delivery to the central nervous system: ADME and molecular docking studies

PubMed Central

Shityakov, Sergey; Broscheit, Jens; Förster, Carola

2012-01-01

This paper attempts to predict and emphasize molecular interactions of dopamine, levodopa, and their derivatives (Dopimid compounds) containing 2-phenyl-imidazopyridine moiety with the α-cyclodextrin dimer in order to assess and improve drug delivery to the central nervous system. The molecular docking method is used to determine the energetic profiles, hydrogen bond formation, and hydrophobic effect of 14 host–guest complexes. The results show that the “chemical branching” represented by additional ethyl-acetate residue is energetically unfavorable and promotes a conformational shift due to the high root mean square deviation levels. This phenomenon is characterized by a low number of H-bonds and a significant decrease of the host–guest hydrophobic potential surface. Finally, the overall docking procedure presents a powerful rationale for screening and analyzing various sets of promising drug-like chemical compounds in the fields of supramolecular chemistry, molecular sensing, synthetic receptors, and nanobiotechnology. PMID:22811606

Chemical Analysis and Water Recovery Testing of Shuttle-Mir Humidity Condensate

NASA Technical Reports Server (NTRS)

Mudgett, Paul D.; Straub, John E., II; Schultz, John R.; Sauer, Richard L.; Williams, David E.; Bobe, L. S.; Novikov, V. M.; Andreichouk, P. O.; Protasov, N. N.

1999-01-01

Humidity condensate collected and processed in-flight is an important component of a space station drinking water supply. Water recovery systems in general are designed to handle finite concentrations of specific chemical components. Previous analyses of condensate derived from spacecraft and ground sources showed considerable variation in composition. Consequently, an investigation was conducted to collect condensate on the Shuttle while the vehicle was docked to Mir, and return the condensate to Earth for testing. This scenario emulates an early ISS configuration during a Shuttle docking, because the atmospheres intermix during docking and the condensate composition should reflect that. During the STS-89 and STS-91 flights, a total volume of 50 liters of condensate was collected and returned. Inorganic and organic chemical analyses were performed on aliquots of the fluid. Tests using the actual condensate were then conducted with scaled-down elements of the Russian condensate recovery system to determine the quality of water produced. The composition and test results are described, and implications for ISS are discussed.

Application of fuzzy logic-neural network based reinforcement learning to proximity and docking operations

NASA Technical Reports Server (NTRS)

Jani, Yashvant

1992-01-01

As part of the Research Institute for Computing and Information Systems (RICIS) activity, the reinforcement learning techniques developed at Ames Research Center are being applied to proximity and docking operations using the Shuttle and Solar Max satellite simulation. This activity is carried out in the software technology laboratory utilizing the Orbital Operations Simulator (OOS). This interim report provides the status of the project and outlines the future plans.

View of STS-100 orbiter Endeavour approaching for docking

NASA Image and Video Library

2001-04-21

ISS002-E-5876 (21 April 2001) --- A distant view of the Space Shuttle Endeavour preparing to dock with the International Space Station (ISS) during the STS-100 mission. The STS-100 crewmembers are delivering the Canadarm2, Space Station Remote Manipulator System (SSRMS), and equipment stowed in the Multipurpose Logistics Module (MPLM) Raphaello to the ISS which are visible in Endeavour's payload bay. The image was taken with a digital still camera.

View of STS-100 orbiter Endeavour approaching for docking

NASA Image and Video Library

2001-04-21

ISS002-E-5887 (21 April 2001) --- A view of the Space Shuttle Endeavour preparing to dock with the International Space Station (ISS) during the STS-100 mission. The STS-100 crewmembers are delivering the Canadarm2, Space Station Remote Manipulator System (SSRMS), and equipment stowed in the Multipurpose Logistics Module (MPLM) Raphaello to the ISS which are visible in Endeavour's payload bay. The image was taken with a digital still camera.

Is It Reliable to Take the Molecular Docking Top Scoring Position as the Best Solution without Considering Available Structural Data?

PubMed

Ramírez, David; Caballero, Julio

2018-04-28

Molecular docking is the most frequently used computational method for studying the interactions between organic molecules and biological macromolecules. In this context, docking allows predicting the preferred pose of a ligand inside a receptor binding site. However, the selection of the “best” solution is not a trivial task, despite the widely accepted selection criterion that the best pose corresponds to the best energy score. Here, several rigid-target docking methods were evaluated on the same dataset with respect to their ability to reproduce crystallographic binding orientations, to test if the best energy score is a reliable criterion for selecting the best solution. For this, two experiments were performed: (A) to reconstruct the ligand-receptor complex by performing docking of the ligand in its own crystal structure receptor (defined as self-docking), and (B) to reconstruct the ligand-receptor complex by performing docking of the ligand in a crystal structure receptor that contains other ligand (defined as cross-docking). Root-mean square deviation (RMSD) was used to evaluate how different the obtained docking orientation is from the corresponding co-crystallized pose of the same ligand molecule. We found that docking score function is capable of predicting crystallographic binding orientations, but the best ranked solution according to the docking energy is not always the pose that reproduces the experimental binding orientation. This happened when self-docking was achieved, but it was critical in cross-docking. Taking into account that docking is typically used with predictive purposes, during cross-docking experiments, our results indicate that the best energy score is not a reliable criterion to select the best solution in common docking applications. It is strongly recommended to choose the best docking solution according to the scoring function along with additional structural criteria described for analogue ligands to assure the selection of a correct docking solution.

Fluorescence spectroscopic and molecular docking studies of the binding interaction between the new anaplastic lymphoma kinase inhibitor crizotinib and bovine serum albumin

NASA Astrophysics Data System (ADS)

Abdelhameed, Ali S.; Alanazi, Amer M.; Bakheit, Ahmed H.; Darwish, Hany W.; Ghabbour, Hazem A.; Darwish, Ibrahim A.

2017-01-01

Binding of the recently introduced anti-cancer drug, crizotinib (CRB) with the bovine serum albumin (BSA) was comprehensively studied with the aid of fluorescence and UV-Vis spectroscopic as well as molecular docking techniques. The collective results of the study under the simulated physiological conditions proposed a static type of binding occurring between the CRB and BSA with binding constants of 104 L mol- 1. BSA conformational changes were investigated using three dimensional (3D) and synchronous fluorescence measurements. Moreover, the results of site marker competitive experiments and molecular docking, it could be deduced that CRB was inserted into the subdomain IIA (site I) of BSA yielding a more stabilized system. This was further confirmed with the molecular docking results which revealed that CRB is located in the active site residues Try149, Glu152, Ser191, Arg194, Arg198, Trp213, Arg217, Arg256, His287, Ala290, Glu291, Ser343, Asp450 within a radius of 6 Å. Combining the molecular docking studies and the computed thermodynamic parameters, it can be inferred that hydrophobic and electrostatic interactions are the major binding forces involved in formation of the CRB-BSA complex.

Shape based virtual screening and molecular docking towards designing novel pancreatic lipase inhibitors

PubMed Central

Veeramachaneni, Ganesh Kumar; Raj, K Kranthi; Chalasani, Leela Madhuri; Annamraju, Sai Krishna; JS, Bondili; Talluri, Venkateswara Rao

2015-01-01

Increase in obesity rates and obesity associated health issues became one of the greatest health concerns in the present world population. With alarming increase in obese percentage there is a need to design new drugs related to the obesity targets. Among the various targets linked to obesity, pancreatic lipase was one of the promising targets for obesity treatment. Using the in silico methods like structure based virtual screening, QikProp, docking studies and binding energy calculations three molecules namely zinc85531017, zinc95919096 and zinc33963788 from the natural database were reported as the potential inhibitors for the pancreatic lipase. Among them zinc95919096 presented all the interactions matching to both standard and crystal ligand and hence it can be further proceeded to drug discovery process. PMID:26770027

Replica Exchange Improves Sampling in Low-Resolution Docking Stage of RosettaDock

PubMed Central

Zhang, Zhe; Lange, Oliver F.

2013-01-01

Many protein-protein docking protocols are based on a shotgun approach, in which thousands of independent random-start trajectories minimize the rigid-body degrees of freedom. Another strategy is enumerative sampling as used in ZDOCK. Here, we introduce an alternative strategy, ReplicaDock, using a small number of long trajectories of temperature replica exchange. We compare replica exchange sampling as low-resolution stage of RosettaDock with RosettaDock's original shotgun sampling as well as with ZDOCK. A benchmark of 30 complexes starting from structures of the unbound binding partners shows improved performance for ReplicaDock and ZDOCK when compared to shotgun sampling at equal or less computational expense. ReplicaDock and ZDOCK consistently reach lower energies and generate significantly more near-native conformations than shotgun sampling. Accordingly, they both improve typical metrics of prediction quality of complex structures after refinement. Additionally, the refined ReplicaDock ensembles reach significantly lower interface energies and many previously hidden features of the docking energy landscape become visible when ReplicaDock is applied. PMID:24009670

BP-Dock: A Flexible Docking Scheme for Exploring Protein–Ligand Interactions Based on Unbound Structures

PubMed Central

Bolia, Ashini; Gerek, Z. Nevin; Ozkan, S. Banu

2016-01-01

Molecular docking serves as an important tool in modeling protein–ligand interactions. However, it is still challenging to incorporate overall receptor flexibility, especially backbone flexibility, in docking due to the large conformational space that needs to be sampled. To overcome this problem, we developed a novel flexible docking approach, BP-Dock (Backbone Perturbation-Dock) that can integrate both backbone and side chain conformational changes induced by ligand binding through a multi-scale approach. In the BP-Dock method, we mimic the nature of binding-induced events as a first-order approximation by perturbing the residues along the protein chain with a small Brownian kick one at a time. The response fluctuation profile of the chain upon these perturbations is computed using the perturbation response scanning method. These response fluctuation profiles are then used to generate binding-induced multiple receptor conformations for ensemble docking. To evaluate the performance of BP-Dock, we applied our approach on a large and diverse data set using unbound structures as receptors. We also compared the BP-Dock results with bound and unbound docking, where overall receptor flexibility was not taken into account. Our results highlight the importance of modeling backbone flexibility in docking for recapitulating the experimental binding affinities, especially when an unbound structure is used. With BP-Dock, we can generate a wide range of binding site conformations realized in nature even in the absence of a ligand that can help us to improve the accuracy of unbound docking. We expect that our fast and efficient flexible docking approach may further aid in our understanding of protein–ligand interactions as well as virtual screening of novel targets for rational drug design. PMID:24380381

DockRank: Ranking docked conformations using partner-specific sequence homology-based protein interface prediction

PubMed Central

Xue, Li C.; Jordan, Rafael A.; EL-Manzalawy, Yasser; Dobbs, Drena; Honavar, Vasant

2015-01-01

Selecting near-native conformations from the immense number of conformations generated by docking programs remains a major challenge in molecular docking. We introduce DockRank, a novel approach to scoring docked conformations based on the degree to which the interface residues of the docked conformation match a set of predicted interface residues. Dock-Rank uses interface residues predicted by partner-specific sequence homology-based protein–protein interface predictor (PS-HomPPI), which predicts the interface residues of a query protein with a specific interaction partner. We compared the performance of DockRank with several state-of-the-art docking scoring functions using Success Rate (the percentage of cases that have at least one near-native conformation among the top m conformations) and Hit Rate (the percentage of near-native conformations that are included among the top m conformations). In cases where it is possible to obtain partner-specific (PS) interface predictions from PS-HomPPI, DockRank consistently outperforms both (i) ZRank and IRAD, two state-of-the-art energy-based scoring functions (improving Success Rate by up to 4-fold); and (ii) Variants of DockRank that use predicted interface residues obtained from several protein interface predictors that do not take into account the binding partner in making interface predictions (improving success rate by up to 39-fold). The latter result underscores the importance of using partner-specific interface residues in scoring docked conformations. We show that DockRank, when used to re-rank the conformations returned by ClusPro, improves upon the original ClusPro rankings in terms of both Success Rate and Hit Rate. DockRank is available as a server at http://einstein.cs.iastate.edu/DockRank/. PMID:23873600

DockRank: ranking docked conformations using partner-specific sequence homology-based protein interface prediction.

PubMed

Xue, Li C; Jordan, Rafael A; El-Manzalawy, Yasser; Dobbs, Drena; Honavar, Vasant

2014-02-01

Selecting near-native conformations from the immense number of conformations generated by docking programs remains a major challenge in molecular docking. We introduce DockRank, a novel approach to scoring docked conformations based on the degree to which the interface residues of the docked conformation match a set of predicted interface residues. DockRank uses interface residues predicted by partner-specific sequence homology-based protein-protein interface predictor (PS-HomPPI), which predicts the interface residues of a query protein with a specific interaction partner. We compared the performance of DockRank with several state-of-the-art docking scoring functions using Success Rate (the percentage of cases that have at least one near-native conformation among the top m conformations) and Hit Rate (the percentage of near-native conformations that are included among the top m conformations). In cases where it is possible to obtain partner-specific (PS) interface predictions from PS-HomPPI, DockRank consistently outperforms both (i) ZRank and IRAD, two state-of-the-art energy-based scoring functions (improving Success Rate by up to 4-fold); and (ii) Variants of DockRank that use predicted interface residues obtained from several protein interface predictors that do not take into account the binding partner in making interface predictions (improving success rate by up to 39-fold). The latter result underscores the importance of using partner-specific interface residues in scoring docked conformations. We show that DockRank, when used to re-rank the conformations returned by ClusPro, improves upon the original ClusPro rankings in terms of both Success Rate and Hit Rate. DockRank is available as a server at http://einstein.cs.iastate.edu/DockRank/. Copyright © 2013 Wiley Periodicals, Inc.

ConsDock: A new program for the consensus analysis of protein-ligand interactions.

PubMed

Paul, Nicodème; Rognan, Didier

2002-06-01

Protein-based virtual screening of chemical libraries is a powerful technique for identifying new molecules that may interact with a macromolecular target of interest. Because of docking and scoring limitations, it is more difficult to apply as a lead optimization method because it requires that the docking/scoring tool is able to propose as few solutions as possible and all of them with a very good accuracy for both the protein-bound orientation and the conformation of the ligand. In the present study, we present a consensus docking approach (ConsDock) that takes advantage of three widely used docking tools (Dock, FlexX, and Gold). The consensus analysis of all possible poses generated by several docking tools is performed sequentially in four steps: (i) hierarchical clustering of all poses generated by a docking tool into families represented by a leader; (ii) definition of all consensus pairs from leaders generated by different docking programs; (iii) clustering of consensus pairs into classes, represented by a mean structure; and (iv) ranking the different means starting from the most populated class of consensus pairs. When applied to a test set of 100 protein-ligand complexes from the Protein Data Bank, ConsDock significantly outperforms single docking with respect to the docking accuracy of the top-ranked pose. In 60% of the cases investigated here, ConsDock was able to rank as top solution a pose within 2 A RMSD of the X-ray structure. It can be applied as a postprocessing filter to either single- or multiple-docking programs to prioritize three-dimensional guided lead optimization from the most likely docking solution. Copyright 2002 Wiley-Liss, Inc.

GalaxyDock BP2 score: a hybrid scoring function for accurate protein-ligand docking

NASA Astrophysics Data System (ADS)

Baek, Minkyung; Shin, Woong-Hee; Chung, Hwan Won; Seok, Chaok

2017-07-01

Protein-ligand docking is a useful tool for providing atomic-level understanding of protein functions in nature and design principles for artificial ligands or proteins with desired properties. The ability to identify the true binding pose of a ligand to a target protein among numerous possible candidate poses is an essential requirement for successful protein-ligand docking. Many previously developed docking scoring functions were trained to reproduce experimental binding affinities and were also used for scoring binding poses. However, in this study, we developed a new docking scoring function, called GalaxyDock BP2 Score, by directly training the scoring power of binding poses. This function is a hybrid of physics-based, empirical, and knowledge-based score terms that are balanced to strengthen the advantages of each component. The performance of the new scoring function exhibits significant improvement over existing scoring functions in decoy pose discrimination tests. In addition, when the score is used with the GalaxyDock2 protein-ligand docking program, it outperformed other state-of-the-art docking programs in docking tests on the Astex diverse set, the Cross2009 benchmark set, and the Astex non-native set. GalaxyDock BP2 Score and GalaxyDock2 with this score are freely available at http://galaxy.seoklab.org/softwares/galaxydock.html.

PPI4DOCK: large scale assessment of the use of homology models in free docking over more than 1000 realistic targets.

PubMed

Yu, Jinchao; Guerois, Raphaël

2016-12-15

Protein-protein docking methods are of great importance for understanding interactomes at the structural level. It has become increasingly appealing to use not only experimental structures but also homology models of unbound subunits as input for docking simulations. So far we are missing a large scale assessment of the success of rigid-body free docking methods on homology models. We explored how we could benefit from comparative modelling of unbound subunits to expand docking benchmark datasets. Starting from a collection of 3157 non-redundant, high X-ray resolution heterodimers, we developed the PPI4DOCK benchmark containing 1417 docking targets based on unbound homology models. Rigid-body docking by Zdock showed that for 1208 cases (85.2%), at least one correct decoy was generated, emphasizing the efficiency of rigid-body docking in generating correct assemblies. Overall, the PPI4DOCK benchmark contains a large set of realistic cases and provides new ground for assessing docking and scoring methodologies. Benchmark sets can be downloaded from http://biodev.cea.fr/interevol/ppi4dock/ CONTACT: guerois@cea.frSupplementary information: Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

American & Soviet engineers examine ASTP docking set-up following tests

NASA Image and Video Library

1974-07-10

S74-25394 (10 July 1974) --- A group of American and Soviet engineers of the Apollo-Soyuz Test Project working group three examines an ASTP docking set-up following a docking mechanism fitness test conducted in Building 13 at the Johnson Space Center. Working Group No. 3 is concerned with ASTP docking problems and techniques. The joint U.S.-USSR ASTP docking mission in Earth orbit is scheduled for the summer of 1975. The Apollo docking mechanism is atop the Soyuz docking mechanism.

Interaction of the minocycline with extracelluar protein and intracellular protein by multi-spectral techniques and molecular docking

NASA Astrophysics Data System (ADS)

Fang, Qing; Wang, Yirun; Hu, Taoying; Liu, Ying

2017-02-01

The interaction of minocyeline (MNC) with extracelluar protein (lysozyme, LYSO) or intracellular protein (bovine hemoglobin, BHb) was investigated using multi-spectral techniques and molecular docking in vitro. Fluorescence studies suggested that MNC quenched LYSO/BHb fluorescence in a static mode with binding constants of 2.01 and 0.26 × 104 L•mol-1 at 298 K, respectively. The LYZO-MNC system was more easily influenced by temperature (298 and 310 K) than the BHb-MNC system. The thermodynamic parameters demonstrated that hydrogen bonds and van der Waals forces played the major role in the binding process. Based on the Förster theory of nonradiative energy transfer, the binding distances between MNC and the inner tryptophan residues of LYSO and BHb were calculated to be 4.34 and 3.49 nm, respectively. Furthermore, circular dichroism spectra (CD), Fourier transforms infrared (FTIR), UV-vis, and three-dimensional fluorescence spectra results indicated the secondary structures of LYSO and BHb were partially destroyed by MNC with the α-helix percentage of LYZO-MNC increased (17.8-28.6%) while that of BHb-MNC was decreased (41.6-39.6%). UV-vis spectral results showed these binding interactions could cause conformational and some micro-environmental changes of LYSO and BHb. In accordance with the results of molecular docking, In LYZO-MNC system, MNC was mainly bound in the active site hinge region where Trp-62 and Trp-63 are located, and in MNC-BHb system, MNC was close to the subunit α 1 of BHb, molecular docking analysis supported the thermodynamic results well. The work contributes to clarify the mechanism of MNC with two proteins at molecular level.

Multi-Sensor Testing for Automated Rendezvous and Docking Sensor Testing at the Flight Robotics Lab

NASA Technical Reports Server (NTRS)

Brewster, Linda L.; Howard, Richard T.; Johnston, A. S.; Carrington, Connie; Mitchell, Jennifer D.; Cryan, Scott P.

2008-01-01

The Exploration Systems Architecture defines missions that require rendezvous, proximity operations, and docking (RPOD) of two spacecraft both in Low Earth Orbit (LEO) and in Low Lunar Orbit (LLO). Uncrewed spacecraft must perform automated and/or autonomous rendezvous, proximity operations and docking operations (commonly known as AR&D). The crewed missions may also perform rendezvous and docking operations and may require different levels of automation and/or autonomy, and must provide the crew with relative navigation information for manual piloting. The capabilities of the RPOD sensors are critical to the success ofthe Exploration Program. NASA has the responsibility to determine whether the Crew Exploration Vehicle (CEV) contractor-proposed relative navigation sensor suite will meet the requirements. The relatively low technology readiness level of AR&D relative navigation sensors has been carried as one of the CEV Project's top risks. The AR&D Sensor Technology Project seeks to reduce the risk by the testing and analysis of selected relative navigation sensor technologies through hardware-in-the-Ioop testing and simulation. These activities will provide the CEV Project information to assess the relative navigation sensors maturity as well as demonstrate test methods and capabilities. The first year of this project focused on a series of "pathfinder" testing tasks to develop the test plans, test facility requirements, trajectories, math model architecture, simulation platform, and processes that will be used to evaluate the Contractor-proposed sensors. Four candidate sensors were used in the first phase of the testing. The second phase of testing used four sensors simultaneously: two Marshall Space Flight Center (MSFC) Advanced Video Guidance Sensors (AVGS), a laser-based video sensor that uses retroreflectors attached to the target vehicle, and two commercial laser range finders. The multi-sensor testing was conducted at MSFC's Flight Robotics Laboratory (FRL) using the FRL's 6-DOF gantry system, called the Dynamic Overhead Target System (DOTS). The target vehicle for "docking" in the laboratory was a mockup that was representative of the proposed CEV docking system, with added retroreflectors for the AVGS.' The multi-sensor test configuration used 35 open-loop test trajectories covering three major objectives: (l) sensor characterization trajectories designed to test a wide range of performance parameters; (2) CEV-specific trajectories designed to test performance during CEV-like approach and departure profiles; and (3) sensor characterization tests designed for evaluating sensor performance under more extreme conditions as might be induced during a spacecraft failure or during contingency situations. This paper describes the test development, test facility, test preparations, test execution, and test results of the multisensor series oftrajectories

Comparative evaluation of several docking tools for docking small molecule ligands to DC-SIGN.

PubMed

Jug, Gregor; Anderluh, Marko; Tomašič, Tihomir

2015-06-01

Five docking tools, namely AutoDock, FRED, CDOCKER, FlexX and GOLD, have been critically examined, with the aim of selecting those most appropriate for use as docking tools for docking molecules to the lectin dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN). This lectin has been selected for its rather non-druggable binding site, which enables complex interactions that guide the binding of the core monosaccharide. Since optimal orientation is crucial for forming coordination bonds, it was important to assess whether the selected docking tools could reproduce the optimal binding conformation for several oligosaccharides that are known to bind DC-SIGN. Our results show that even widely used docking programs have certain limitations when faced with a rather shallow and featureless binding site, as is the case of DC-SIGN. The FRED docking software (OpenEye Scientific Software, Inc.) was found to score as the best tool for docking ligands to DC-SIGN. The performance of FRED was further assessed on another lectin, Langerin. We have demonstrated that this validated docking protocol could be used for docking to other lectins similar to DC-SIGN.

Domain wise docking analyses of the modular chitin binding protein CBP50 from Bacillus thuringiensis serovar konkukian S4.

PubMed

Sehar, Ujala; Mehmood, Muhammad Aamer; Hussain, Khadim; Nawaz, Salman; Nadeem, Shahid; Siddique, Muhammad Hussnain; Nadeem, Habibullah; Gull, Munazza; Ahmad, Niaz; Sohail, Iqra; Gill, Saba Shahid; Majeed, Summera

2013-01-01

This paper presents an in silico characterization of the chitin binding protein CBP50 from B. thuringiensis serovar konkukian S4 through homology modeling and molecular docking. The CBP50 has shown a modular structure containing an N-terminal CBM33 domain, two consecutive fibronectin-III (Fn-III) like domains and a C-terminal CBM5 domain. The protein presented a unique modular structure which could not be modeled using ordinary procedures. So, domain wise modeling using MODELLER and docking analyses using Autodock Vina were performed. The best conformation for each domain was selected using standard procedure. It was revealed that four amino acid residues Glu-71, Ser-74, Glu-76 and Gln-90 from N-terminal domain are involved in protein-substrate interaction. Similarly, amino acid residues Trp-20, Asn-21, Ser-23 and Val-30 of Fn-III like domains and Glu-15, Ala-17, Ser-18 and Leu-35 of C-terminal domain were involved in substrate binding. Site-directed mutagenesis of these proposed amino acid residues in future will elucidate the key amino acids involved in chitin binding activity of CBP50 protein.

Emission rates of regulated pollutants from current technology heavy-duty diesel and natural gas goods movement vehicles.

PubMed

Thiruvengadam, Arvind; Besch, Marc C; Thiruvengadam, Pragalath; Pradhan, Saroj; Carder, Daniel; Kappanna, Hemanth; Gautam, Mridul; Oshinuga, Adewale; Hogo, Henry; Miyasato, Matt

2015-04-21

Chassis dynamometer emissions testing of 11 heavy-duty goods movement vehicles, including diesel, natural gas, and dual-fuel technology, compliant with US-EPA 2010 emissions standard were conducted. Results of the study show that three-way catalyst (TWC) equipped stoichiometric natural gas vehicles emit 96% lower NOx emissions as compared to selective catalytic reduction (SCR) equipped diesel vehicles. Characteristics of drayage truck vocation, represented by the near-dock and local drayage driving cycles, were linked to high NOx emissions from diesel vehicles equipped with a SCR. Exhaust gas temperatures below 250 °C, for more than 95% duration of the local and near-dock driving cycles, resulted in minimal SCR activity. The low percentage of activity SCR over the local and near-dock cycles contributed to a brake-specific NOx emissions that were 5-7 times higher than in-use certification limit. The study also illustrated the differences between emissions rate measured from chassis dynamometer testing and prediction from the EMFAC model. The results of the study emphasize the need for model inputs relative to SCR performance as a function of driving cycle and engine operation characteristics.

Anti-tubercular agents from Glycyrrhiza glabra.

PubMed

Kalani, Komal; Chaturvedi, Vinita; Alam, Sarfaraz; Khan, Feroz; Srivastava, Santosh Kumar

2015-01-01

Bioactivity guided isolation of Glycyrrhiza glabra (Leguminosae / Fabaceae) roots resulted in the characterization of 18β-glycyrrhetinic acid as a major anti-tubercular agent. Further, GA-1 was semi-synthetically converted into its nine derivatives, which were in-vitro evaluated for their antitubercular potential against Mycobacterium tuberculosis H37Rv using BACTEC-460 radiometric susceptibility assay. All the derivatives were active, but the benzylamide (GA-8, MIC 12.5μg/ml) and ethyl oxylate (GA-3, MIC 25.0 μg/ml) derivatives were significantly active against the pathogen. This was further supported by the molecular docking studies, which showed adequate docking (LibDock) scores for GA-3 (120.3) and GA-8 (112.6) with respect to the standard anti-tubercular drug, rifampicin (92.94) on the DNA-directed RNA polymerase subunit beta (rpoB) target site. Finally, the in silico pharmacokinetic and drug-likeness studies showed that GA-3 and GA- 8 possesses drug-like properties. This is the first ever report on the anti-tubercular potential of GA and its derivatives. These results may be of great help in anti-tubercular drug development from a very common, inexpensive, and non toxic natural product.

U.S. Army Research Laboratory (ARL) XPairIt Simulator for Peptide Docking and Analysis

DTIC Science & Technology

2014-07-01

results from a case study, docking a short peptide to a small protein. For this test we choose the 1RXZ system from the Protein Data Bank, which...estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data ...core of XPairIt, which additionally contains many data management and organization options, analysis tools, and custom simulation methodology. Two

Rendezvous and docking tracker

NASA Technical Reports Server (NTRS)

Ray, Art J.; Ross, Susan E.; Deming, Douglas R.

1986-01-01

A conceptual solid-state rendezvous and docking tracker (RDT) has been devised for generating range and attitude data for a docking vehicle relative to a target vehicle. Emphasis is placed on the approach of the Orbiter to a link with the Space Station. Three laser illuminators ring the optical axis of the lens a directed toward retroreflectors on the target vehicle. Each retroreflector is equipped with a bandpass filter for a designated illumination frequency. Data are collected sequentially over a 20 deg field of view as the range closes to 100-1000 m. A fourth ranging retroreflector 0.3 m from center is employed during close-in maneuvers. The system provides tracking data on motions with 6 deg of freedom, and furnishes 500 msec updates (to be enhanced to 100 msec) to the operator at a computer console.

Study of and proposals for the correction of errors in a radar ranging device designed to facilitate docking of a teleoperator maneuvering system

NASA Technical Reports Server (NTRS)

Mcdonald, M. W.

1982-01-01

A frequency modulated continuous wave radar system was developed. The system operates in the 35 gigahertz frequency range and provides millimeter accuracy range and range rate measurements. This level of range resolution allows soft docking for the proposed teleoperator maneuvering system (TMS) or other autonomous or robotic space vehicles. Sources of error in the operation of the system which tend to limit its range resolution capabilities are identified. Alternative signal processing techniques are explored with emphasis on determination of the effects of inserting various signal filtering circuits in the system. The identification and elimination of an extraneous low frequency signal component created as a result of zero range immediate reflection of radar energy from the surface of the antenna dish back into the mixer of the system is described.

Neural networks for self-learning control systems

NASA Technical Reports Server (NTRS)

Nguyen, Derrick H.; Widrow, Bernard

1990-01-01

It is shown how a neural network can learn of its own accord to control a nonlinear dynamic system. An emulator, a multilayered neural network, learns to identify the system's dynamic characteristics. The controller, another multilayered neural network, next learns to control the emulator. The self-trained controller is then used to control the actual dynamic system. The learning process continues as the emulator and controller improve and track the physical process. An example is given to illustrate these ideas. The 'truck backer-upper,' a neural network controller that steers a trailer truck while the truck is backing up to a loading dock, is demonstrated. The controller is able to guide the truck to the dock from almost any initial position. The technique explored should be applicable to a wide variety of nonlinear control problems.

A study of 35-ghz radar-assisted orbital maneuvering vehicle/space telescope docking

NASA Technical Reports Server (NTRS)

Mcdonald, M. W.

1986-01-01

An experiment was conducted to study the effects of measuring range and range rate information from a complex radar target (a one-third scale model of the Edwin P. Hubble Space Telescope). The radar ranging system was a 35-GHz frequency-modulated continuous wave unit developed in the Communication Systems Branch of the Information and Electronic Systems Laboratory at Marshall Space Flight Cneter. Measurements were made over radar-to-target distances of 5 meters to 15 meters to simulate the close distance realized in the final stages of space vehicle docking. The Space Telescope model target was driven by an antenna positioner through a range of azimuth and elevation (pitch) angles to present a variety of visual aspects of the aft end to the radar. Measurements were obtained with and without a cube corner reflector mounted in the center of the aft end of the model. The results indicate that range and range rate measurements are performed significantly more accurately with the cooperative radar reflector affixed. The results further reveal that range rate (velocity) can be measured accurately enough to support the required soft docking with the Space Telescope.

A Mission Concept: Re-Entry Hopper-Aero-Space-Craft System on-Mars (REARM-Mars)

NASA Technical Reports Server (NTRS)

Davoodi, Faranak

2013-01-01

Future missions to Mars that would need a sophisticated lander, hopper, or rover could benefit from the REARM Architecture. The mission concept REARM Architecture is designed to provide unprecedented capabilities for future Mars exploration missions, including human exploration and possible sample-return missions, as a reusable lander, ascend/descend vehicle, refuelable hopper, multiple-location sample-return collector, laboratory, and a cargo system for assets and humans. These could all be possible by adding just a single customized Re-Entry-Hopper-Aero-Space-Craft System, called REARM-spacecraft, and a docking station at the Martian orbit, called REARM-dock. REARM could dramatically decrease the time and the expense required to launch new exploratory missions on Mars by making them less dependent on Earth and by reusing the assets already designed, built, and sent to Mars. REARM would introduce a new class of Mars exploration missions, which could explore much larger expanses of Mars in a much faster fashion and with much more sophisticated lab instruments. The proposed REARM architecture consists of the following subsystems: REARM-dock, REARM-spacecraft, sky-crane, secure-attached-compartment, sample-return container, agile rover, scalable orbital lab, and on-the-road robotic handymen.

Gemini Rendezvous Docking Simulator

NASA Image and Video Library

1964-05-11

Gemini Rendezvous Docking Simulator suspended from the roof of the Langley Research Center s aircraft hangar. Francis B. Smith wrote: The rendezvous and docking operation of the Gemini spacecraft with the Agena and of the Apollo Command Module with the Lunar Excursion Module have been the subject of simulator studies for several years. This figure illustrates the Gemini-Agena rendezvous docking simulator at Langley. The Gemini spacecraft was supported in a gimbal system by an overhead crane and gantry arrangement which provided 6 degrees of freedom - roll, pitch, yaw, and translation in any direction - all controllable by the astronaut in the spacecraft. Here again the controls fed into a computer which in turn provided an input to the servos driving the spacecraft so that it responded to control motions in a manner which accurately simulated the Gemini spacecraft. -- Published in Barton C. Hacker and James M. Grimwood, On the Shoulders of Titans: A History of Project Gemini, NASA SP-4203 Francis B. Smith, Simulators for Manned Space Research, Paper presented at the 1966 IEEE International convention, March 21-25, 1966.

Automated Rendezvous and Docking Sensor Testing at the Flight Robotics Laboratory

NASA Technical Reports Server (NTRS)

Mitchell, J.; Johnston, A.; Howard, R.; Williamson, M.; Brewster, L.; Strack, D.; Cryan, S.

2007-01-01

The Exploration Systems Architecture defines missions that require rendezvous, proximity operations, and docking (RPOD) of two spacecraft both in Low Earth Orbit (LEO) and in Low Lunar Orbit (LLO). Uncrewed spacecraft must perform automated and/or autonomous rendezvous, proximity operations and docking operations (commonly known as Automated Rendezvous and Docking, AR&D). The crewed versions may also perform AR&D, possibly with a different level of automation and/or autonomy, and must also provide the crew with relative navigation information for manual piloting. The capabilities of the RPOD sensors are critical to the success of the Exploration Program. NASA has the responsibility to determine whether the Crew Exploration Vehicle (CEV) contractor-proposed relative navigation sensor suite will meet the CEV requirements. The relatively low technology readiness of relative navigation sensors for AR&D has been carried as one of the CEV Projects top risks. The AR&D Sensor Technology Project seeks to reduce this risk by increasing technology maturation of selected relative navigation sensor technologies through testing and simulation, and to allow the CEV Project to assess the relative navigation sensors.

Automated Rendezvous and Docking Sensor Testing at the Flight Robotics Laboratory

NASA Technical Reports Server (NTRS)

Howard, Richard T.; Williamson, Marlin L.; Johnston, Albert S.; Brewster, Linda L.; Mitchell, Jennifer D.; Cryan, Scott P.; Strack, David; Key, Kevin

2007-01-01

The Exploration Systems Architecture defines missions that require rendezvous, proximity operations, and docking (RPOD) of two spacecraft both in Low Earth Orbit (LEO) and in Low Lunar Orbit (LLO). Uncrewed spacecraft must perform automated and/or autonomous rendezvous, proximity operations and docking operations (commonly known as Automated Rendezvous and Docking, (AR&D).) The crewed versions of the spacecraft may also perform AR&D, possibly with a different level of automation and/or autonomy, and must also provide the crew with relative navigation information for manual piloting. The capabilities of the RPOD sensors are critical to the success of the Exploration Program. NASA has the responsibility to determine whether the Crew Exploration Vehicle (CEV) contractor-proposed relative navigation sensor suite will meet the CEV requirements. The relatively low technology readiness of relative navigation sensors for AR&D has been carried as one of the CEV Projects top risks. The AR&D Sensor Technology Project seeks to reduce this risk by increasing technology maturation of selected relative navigation sensor technologies through testing and simulation, and to allow the CEV Project to assess the relative navigation sensors.

Habitat Demonstration Unit (HDU) Vertical Cylinder Habitat

NASA Technical Reports Server (NTRS)

Howe, Alan; Kennedy, Kriss J.; Gill, Tracy R.; Tri, Terry O.; Toups, Larry; Howard, Robert I.; Spexarth, Gary R.; Cavanaugh, Stephen; Langford, William M.; Dorsey, John T.

2014-01-01

NASA's Constellation Architecture Team defined an outpost scenario optimized for intensive mobility that uses small, highly mobile pressurized rovers supported by portable habitat modules that can be carried between locations of interest on the lunar surface. A compact vertical cylinder characterizes the habitat concept, where the large diameter maximizes usable flat floor area optimized for a gravity environment and allows for efficient internal layout. The module was sized to fit into payload fairings for the Constellation Ares V launch vehicle, and optimized for surface transport carried by the All-Terrain Hex-Limbed Extra-Terrestrial Explorer (ATHLETE) mobility system. Launch and other loads are carried through the barrel to a top and bottom truss that interfaces with a structural support unit (SSU). The SSU contains self-leveling feet and docking interfaces for Tri-ATHLETE grasping and heavy lift. A pressurized module needed to be created that was appropriate for the lunar environment, could be easily relocated to new locations, and could be docked together in multiples for expanding pressurized volume in a lunar outpost. It was determined that horizontally oriented pressure vessels did not optimize floor area, which takes advantage of the gravity vector for full use. Hybrid hard-inflatable habitats added an unproven degree of complexity that may eventually be worked out. Other versions of vertically oriented pressure vessels were either too big, bulky, or did not optimize floor area. The purpose of the HDU vertical habitat module is to provide pressurized units that can be docked together in a modular way for lunar outpost pressurized volume expansion, and allow for other vehicles, rovers, and modules to be attached to the outpost to allow for IVA (intra-vehicular activity) transfer between them. The module is a vertically oriented cylinder with a large radius to allow for maximal floor area and use of volume. The modular, 5- m-diameter HDU vertical habitat module consists of a 2-m-high barrel with 0.6-mhigh end domes forming the 56-cubicmeter pressure vessel, and a 19-squaremeter floor area. The module has up to four docking ports located orthogonally from each other around the perimeter, and up to one docking port each on the top or bottom end domes. In addition, the module has mounting trusses top and bottom for equipment, and to allow docking with the ATHLETE mobility system. Novel or unique features of the HDU vertical habitat module include the nodelike function with multiple pressure hatches for docking with other versions of itself and other modules and vehicles; the capacity to be carried by an ATHLETE mobility system; and the ability to attach inflatable 'attic' domes to the top for additional pressurized volume.

Concepts for the evolution of the Space Station Program

NASA Technical Reports Server (NTRS)

Michaud, Roger B.; Miller, Ladonna J.; Primeaux, Gary R.

1986-01-01

An evaluation is made of innovative but pragmatic waste management, interior and exterior orbital module construction, Space Shuttle docking, orbital repair operation, and EVA techniques applicable to the NASA Space Station program over the course of its evolution. Accounts are given of the Space Shuttle's middeck extender module, an on-orbit module assembly technique employing 'Pringles' stack-transportable conformal panels, a flexible Shuttle/Space Station docking tunnel, an 'expandable dome' for transfer of objects into the Space Station, and a Space Station dual-hatch system. For EVA operations, pressurized bubbles with articulating manipulator arms and EVA hard suits incorporating maneuvering, life support and propulsion capabilities, as well as an EVA gas propulsion system, are proposed. A Space Station ultrasound cleaning system is also discussed.

Reusable module for the storage, transportation, and supply of multiple propellants in a space environment

NASA Technical Reports Server (NTRS)

Mazanek, Daniel D. (Inventor); Mankins, John C. (Inventor)

2004-01-01

A space module has an outer structure designed for traveling in space, a docking mechanism for facilitating a docking operation therewith in space, a first storage system storing a first propellant that burns as a result of a chemical reaction therein, a second storage system storing a second propellant that burns as a result of electrical energy being added thereto, and a bi-directional transfer interface coupled to each of the first and second storage systems to transfer the first and second propellants into and out thereof. The space module can be part of a propellant supply architecture that includes at least two of the space modules placed in an orbit in space.

iLIDS Simulations and Videos for Docking TIM

NASA Technical Reports Server (NTRS)

Lewis, James L.

2010-01-01

The video shows various aspects of the International Low Impact Docking System, including team members, some production, configuration, mated androgynous iLIDS, SCS Lockdown system, thermal analysis, electrical engineering aspects, the iLIDS control box and emulator, radiation testing at BNL, component environmental testing, component vibration testing, 3G processor board delivery system, GTA vibe test, EMA testbed, hook and hook disassembly, flex shaftdrive assembly, GSE cradle MISSE-6 Columbus, MISSE 6 and 7 seal experiments, actuated full scale seal test rig, LIDS on Hubble, dynamics test prep, EDU 54 mass emulation and SCS, load ring characterization, 6DOF proof test, SCS at 6DOF, machining EEMS and inner ring assembly, APAS assembly, inner ring fitting, rotation stand assembly, EEMS mating, and EEMS proof of concept demonstration.

1. Full SW side of dock as viewed from shore ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

1. Full SW side of dock as viewed from shore at the Oil/Creosote Unloading Dock. This view formed a panorama with photo WA-131-H-5, which shows the Oil/Creosote Unloading Dock. - Pacific Creosoting Plant, West Dock, 5350 Creosote Place, Northeast, Bremerton, Kitsap County, WA

Optical Docking Aid Containing Fresnel Lenses

NASA Technical Reports Server (NTRS)

Pierce, Cole J.

1995-01-01

Proposed device provides self-contained visual cues to aid in docking. Similar to devices used to guide pilots in landing on aircraft carriers. Positions and directions of beams of light give observer visual cues of position relative to docking target point. Optical assemblies generate directed, diverging beams of light that, together, mark approach path to docking point. Conceived for use in docking spacecraft at Space Station Freedom, device adapted to numerous industrial docking and alignment applications.

pyDockWEB: a web server for rigid-body protein-protein docking using electrostatics and desolvation scoring.

PubMed

Jiménez-García, Brian; Pons, Carles; Fernández-Recio, Juan

2013-07-01

pyDockWEB is a web server for the rigid-body docking prediction of protein-protein complex structures using a new version of the pyDock scoring algorithm. We use here a new custom parallel FTDock implementation, with adjusted grid size for optimal FFT calculations, and a new version of pyDock, which dramatically speeds up calculations while keeping the same predictive accuracy. Given the 3D coordinates of two interacting proteins, pyDockWEB returns the best docking orientations as scored mainly by electrostatics and desolvation energy. The server does not require registration by the user and is freely accessible for academics at http://life.bsc.es/servlet/pydock. Supplementary data are available at Bioinformatics online.

Multi-Conformer Ensemble Docking to Difficult Protein Targets

DOE PAGES

Ellingson, Sally R.; Miao, Yinglong; Baudry, Jerome; ...

2014-09-08

We investigate large-scale ensemble docking using five proteins from the Directory of Useful Decoys (DUD, dud.docking.org) for which docking to crystal structures has proven difficult. Molecular dynamics trajectories are produced for each protein and an ensemble of representative conformational structures extracted from the trajectories. Docking calculations are performed on these selected simulation structures and ensemble-based enrichment factors compared with those obtained using docking in crystal structures of the same protein targets or random selection of compounds. We also found simulation-derived snapshots with improved enrichment factors that increased the chemical diversity of docking hits for four of the five selected proteins.more » A combination of all the docking results obtained from molecular dynamics simulation followed by selection of top-ranking compounds appears to be an effective strategy for increasing the number and diversity of hits when using docking to screen large libraries of chemicals against difficult protein targets.« less

DockingApp: a user friendly interface for facilitated docking simulations with AutoDock Vina.

PubMed

Di Muzio, Elena; Toti, Daniele; Polticelli, Fabio

2017-02-01

Molecular docking is a powerful technique that helps uncover the structural and energetic bases of the interaction between macromolecules and substrates, endogenous and exogenous ligands, and inhibitors. Moreover, this technique plays a pivotal role in accelerating the screening of large libraries of compounds for drug development purposes. The need to promote community-driven drug development efforts, especially as far as neglected diseases are concerned, calls for user-friendly tools to allow non-expert users to exploit the full potential of molecular docking. Along this path, here is described the implementation of DockingApp, a freely available, extremely user-friendly, platform-independent application for performing docking simulations and virtual screening tasks using AutoDock Vina. DockingApp sports an intuitive graphical user interface which greatly facilitates both the input phase and the analysis of the results, which can be visualized in graphical form using the embedded JMol applet. The application comes with the DrugBank set of more than 1400 ready-to-dock, FDA-approved drugs, to facilitate virtual screening and drug repurposing initiatives. Furthermore, other databases of compounds such as ZINC, available also in AutoDock format, can be readily and easily plugged in.

DockingApp: a user friendly interface for facilitated docking simulations with AutoDock Vina

NASA Astrophysics Data System (ADS)

Di Muzio, Elena; Toti, Daniele; Polticelli, Fabio

2017-02-01

Molecular docking is a powerful technique that helps uncover the structural and energetic bases of the interaction between macromolecules and substrates, endogenous and exogenous ligands, and inhibitors. Moreover, this technique plays a pivotal role in accelerating the screening of large libraries of compounds for drug development purposes. The need to promote community-driven drug development efforts, especially as far as neglected diseases are concerned, calls for user-friendly tools to allow non-expert users to exploit the full potential of molecular docking. Along this path, here is described the implementation of DockingApp, a freely available, extremely user-friendly, platform-independent application for performing docking simulations and virtual screening tasks using AutoDock Vina. DockingApp sports an intuitive graphical user interface which greatly facilitates both the input phase and the analysis of the results, which can be visualized in graphical form using the embedded JMol applet. The application comes with the DrugBank set of more than 1400 ready-to-dock, FDA-approved drugs, to facilitate virtual screening and drug repurposing initiatives. Furthermore, other databases of compounds such as ZINC, available also in AutoDock format, can be readily and easily plugged in.

Independent signaling by Drosophila insulin receptor for axon guidance and growth.

PubMed

Li, Caroline R; Guo, Dongyu; Pick, Leslie

2013-01-01

The Drosophila insulin receptor (DInR) regulates a diverse array of biological processes including growth, axon guidance, and sugar homeostasis. Growth regulation by DInR is mediated by Chico, the Drosophila homolog of vertebrate insulin receptor substrate proteins IRS1-4. In contrast, DInR regulation of photoreceptor axon guidance in the developing visual system is mediated by the SH2-SH3 domain adaptor protein Dreadlocks (Dock). In vitro studies by others identified five NPXY motifs, one in the juxtamembrane region and four in the signaling C-terminal tail (C-tail), important for interaction with Chico. Here we used yeast two-hybrid assays to identify regions in the DInR C-tail that interact with Dock. These Dock binding sites were in separate portions of the C-tail from the previously identified Chico binding sites. To test whether these sites are required for growth or axon guidance in whole animals, a panel of DInR proteins, in which the putative Chico and Dock interaction sites had been mutated individually or in combination, were tested for their ability to rescue viability, growth and axon guidance defects of dinr mutant flies. Sites required for viability were identified. Unexpectedly, mutation of both putative Dock binding sites, either individually or in combination, did not lead to defects in photoreceptor axon guidance. Thus, either sites also required for viability are necessary for DInR function in axon guidance and/or there is redundancy built into the DInR/Dock interaction such that Dock is able to interact with multiple regions of DInR. We also found that simultaneous mutation of all five NPXY motifs implicated in Chico interaction drastically decreased growth in both male and female adult flies. These animals resembled chico mutants, supporting the notion that DInR interacts directly with Chico in vivo to control body size. Mutation of these five NPXY motifs did not affect photoreceptor axon guidance, segregating the roles of DInR in the processes of growth and axon guidance.

Pharmacophore Based 3D-QSAR, Virtual Screening and Docking Studies on Novel Series of HDAC Inhibitors with Thiophen Linker as Anticancer Agents.

PubMed

Patel, Preeti; Singh, Avineesh; Patel, Vijay K; Jain, Deepak K; Veerasamy, Ravichandran; Rajak, Harish

2016-01-01

Histone deacetylase (HDAC) inhibitors can reactivate gene expression and inhibit the growth and survival of cancer cells. To identify the important pharmacophoric features and correlate 3Dchemical structure with biological activity using 3D-QSAR and Pharmacophore modeling studies. The pharmacophore hypotheses were developed using e-pharmacophore script and phase module. Pharmacophore hypothesis represents the 3D arrangement of molecular features necessary for activity. A series of 55 compounds with wellassigned HDAC inhibitory activity were used for 3D-QSAR model development. Best 3D-QSAR model, which is a five partial least square (PLS) factor model with good statistics and predictive ability, acquired Q2 (0.7293), R2 (0.9811), cross-validated coefficient rcv 2=0.9807 and R2 pred=0.7147 with low standard deviation (0.0952). Additionally, the selected pharmacophore model DDRRR.419 was used as a 3D query for virtual screening against the ZINC database. In the virtual screening workflow, docking studies (HTVS, SP and XP) were carried out by selecting multiple receptors (PDB ID: 1T69, 1T64, 4LXZ, 4LY1, 3MAX, 2VQQ, 3C10, 1W22). Finally, six compounds were obtained based on high scoring function (dock score -11.2278-10.2222 kcal/mol) and diverse structures. The structure activity correlation was established using virtual screening, docking, energetic based pharmacophore modelling, pharmacophore, atom based 3D QSAR models and their validation. The outcomes of these studies could be further employed for the design of novel HDAC inhibitors for anticancer activity.

Protein social behavior makes a stronger signal for partner identification than surface geometry

PubMed Central

Laine, Elodie

2016-01-01

ABSTRACT Cells are interactive living systems where proteins movements, interactions and regulation are substantially free from centralized management. How protein physico‐chemical and geometrical properties determine who interact with whom remains far from fully understood. We show that characterizing how a protein behaves with many potential interactors in a complete cross‐docking study leads to a sharp identification of its cellular/true/native partner(s). We define a sociability index, or S‐index, reflecting whether a protein likes or not to pair with other proteins. Formally, we propose a suitable normalization function that accounts for protein sociability and we combine it with a simple interface‐based (ranking) score to discriminate partners from non‐interactors. We show that sociability is an important factor and that the normalization permits to reach a much higher discriminative power than shape complementarity docking scores. The social effect is also observed with more sophisticated docking algorithms. Docking conformations are evaluated using experimental binding sites. These latter approximate in the best possible way binding sites predictions, which have reached high accuracy in recent years. This makes our analysis helpful for a global understanding of partner identification and for suggesting discriminating strategies. These results contradict previous findings claiming the partner identification problem being solvable solely with geometrical docking. Proteins 2016; 85:137–154. © 2016 Wiley Periodicals, Inc. PMID:27802579

Protein social behavior makes a stronger signal for partner identification than surface geometry.

PubMed

Laine, Elodie; Carbone, Alessandra

2017-01-01

Cells are interactive living systems where proteins movements, interactions and regulation are substantially free from centralized management. How protein physico-chemical and geometrical properties determine who interact with whom remains far from fully understood. We show that characterizing how a protein behaves with many potential interactors in a complete cross-docking study leads to a sharp identification of its cellular/true/native partner(s). We define a sociability index, or S-index, reflecting whether a protein likes or not to pair with other proteins. Formally, we propose a suitable normalization function that accounts for protein sociability and we combine it with a simple interface-based (ranking) score to discriminate partners from non-interactors. We show that sociability is an important factor and that the normalization permits to reach a much higher discriminative power than shape complementarity docking scores. The social effect is also observed with more sophisticated docking algorithms. Docking conformations are evaluated using experimental binding sites. These latter approximate in the best possible way binding sites predictions, which have reached high accuracy in recent years. This makes our analysis helpful for a global understanding of partner identification and for suggesting discriminating strategies. These results contradict previous findings claiming the partner identification problem being solvable solely with geometrical docking. Proteins 2016; 85:137-154. © 2016 Wiley Periodicals, Inc. © 2016 The Authors Proteins: Structure, Function, and Bioinformatics Published by Wiley Periodicals, Inc.

Synthesis, in vitro β-glucuronidase inhibitory potential and molecular docking studies of quinolines.

PubMed

Bano, Bilquees; Arshia; Khan, Khalid Mohammed; Kanwal; Fatima, Bibi; Taha, Muhammad; Ismail, Nor Hadiani; Wadood, Abdul; Ghufran, Mehreen; Perveen, Shahnaz

2017-10-20

In this study synthesis and β-glucuronidase inhibitory potential of 3/5/8 sulfonamide and 8-sulfonate derivatives of quinoline (1-40) are discussed. Studies reveal that all the synthetic compounds were found to have good inhibitory activity against β-glucuronidase. Nonetheless, compounds 1, 2, 5, 13, and 22-24 having IC 50 values in the range of 1.60-8.40 μM showed superior activity than the standard saccharic acid 1,4-lactone (IC 50  = 48.4 ± 1.25 μM). Moreover, molecular docking studies of selected compounds were also performed to see interactions between active compounds and binding sites. Structures of all the synthetic compounds were confirmed through 1 H NMR, EI-MS and HREI-MS spectroscopic techniques. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Dishevelled links basal body docking and orientation in ciliated epithelial cells

PubMed Central

Vladar, Eszter K.; Axelrod, Jeffrey D.

2014-01-01

Some epithelia contain cells with multiple, motile cilia that beat in a concerted fashion. New tools and experimental systems have facilitated molecular studies of cilium biogenesis and of the coordinated planar polarization of cilia that leads to their concerted motility. Recent, elegant work by Park and colleagues, using embryonic frog epidermis, demonstrates that Dishevelled (Dvl), a key regulator of both the Wnt/β-catenin and Planar Cell Polarity (PCP) pathways, controls both the docking and planar polarization of ciliary basal bodies. PMID:18819800

Skylab checkout operations. [from multiple docking adapter contractor viewpoint

NASA Technical Reports Server (NTRS)

Timmons, K. P.

1973-01-01

The Skylab Program at Kennedy Space Center presented many opportunities for interesting and profound test and checkout experience. It also offered a compilation of challenges and promises for the Center and for the contractors responsible for the various modules making up Skylab. It is very probable that the various contractors had common experiences during the module and combined systems tests, but this paper will discuss those experiences from the viewpoint of the Multiple Docking Adapter contractor. The experience will consider personnel, procedures, and hardware.

Definition of spacecraft standard interfaces by the NASA Space Assembly and Servicing Working Group (SASWG)

NASA Technical Reports Server (NTRS)

Radtke, Robert; Woolley, Charles; Arnold, Lana

1993-01-01

The purpose of the NASA Space Assembly and Servicing Working Group (SASWG) is to study enabling technologies for on-orbit spacecraft maintenance and servicing. One key technology required for effective space logistics activity is the development of standard spacecraft interfaces, including the 'Basic Set' defined by NASA, the U.S. Space Command, and industry panelists to be the following: (1) navigation aids; (2) grasping, berthing, and docking; and (3) utility connections for power, data, and fluids. Draft standards have been prepared and referred to professional standards organizations, including the AIAA, EIA, and SAE space standards committee. The objective of the SASWG is to support these committees with the technical expertise required to prepare standards, guidelines, and recommended practices which will be accepted by the ANSI and international standards organizations, including the ISO, IEC, and PASC.

Silencing of dedicator of cytokinesis (DOCK180) obliterates pregnancy by interfering with decidualization due to blockage of nuclear entry of autoimmune regulator (AIRE).

PubMed

Mohan, Jasna Jagan; Narayan, Prashanth; Padmanabhan, Renjini Ambika; Joseph, Selin; Kumar, Pradeep G; Laloraya, Malini

2018-07-01

Dedicator of cytokinesis (DOCK 180) involved in cytoskeletal reorganization is primarily a cytosolic molecule. It is recently shown to be nuclear in HeLa cells but its nuclear function is not known. The spatiotemporal distribution of DOCK180 in uterus was studied in uterine cytoplasmic and nuclear compartments during the "window of implantation." The functional significance of nuclear DOCK180 was explored by homology modeling, co-immunoprecipitation assays, and mass spectrometric analysis. Dock180's role in early pregnancy was ascertained by Dock 180 silencing and subsequent quantitative real-time PCR and Western blotting analysis. Our study shows a nuclear DOCK180 in the uterus during "window of implantation." Estrogen and progesterone mediate expression and nuclear translocation of DOCK180. The nuclear function of DOCK180 is attributed to its ability to import autoimmune regulator (AIRE) into the nucleus. Silencing of Dock180 inhibited AIRE nuclear shuttling which influenced its downstream targets, thereby affecting decidualization with AIRE and HOXA-10 as the major players as well as lack of implantation site formation due to impact on angiogenesis-associated genes. DOCK180 has an indispensable role in pregnancy establishment as knocking down Dock180 abrogates pregnancy by a consolidated impact on decidualization and angiogenesis by regulating AIRE nuclear entry. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

InterEvDock: a docking server to predict the structure of protein–protein interactions using evolutionary information

PubMed Central

Yu, Jinchao; Vavrusa, Marek; Andreani, Jessica; Rey, Julien; Tufféry, Pierre; Guerois, Raphaël

2016-01-01

The structural modeling of protein–protein interactions is key in understanding how cell machineries cross-talk with each other. Molecular docking simulations provide efficient means to explore how two unbound protein structures interact. InterEvDock is a server for protein docking based on a free rigid-body docking strategy. A systematic rigid-body docking search is performed using the FRODOCK program and the resulting models are re-scored with InterEvScore and SOAP-PP statistical potentials. The InterEvScore potential was specifically designed to integrate co-evolutionary information in the docking process. InterEvDock server is thus particularly well suited in case homologous sequences are available for both binding partners. The server returns 10 structures of the most likely consensus models together with 10 predicted residues most likely involved in the interface. In 91% of all complexes tested in the benchmark, at least one residue out of the 10 predicted is involved in the interface, providing useful guidelines for mutagenesis. InterEvDock is able to identify a correct model among the top10 models for 49% of the rigid-body cases with evolutionary information, making it a unique and efficient tool to explore structural interactomes under an evolutionary perspective. The InterEvDock web interface is available at http://bioserv.rpbs.univ-paris-diderot.fr/services/InterEvDock/. PMID:27131368

Synthesis of 6-chloro-2-Aryl-1H-imidazo[4,5-b]pyridine derivatives: Antidiabetic, antioxidant, β-glucuronidase inhibiton and their molecular docking studies.

PubMed

Taha, Muhammad; Ismail, Nor Hadiani; Imran, Syahrul; Rashwan, Hesham; Jamil, Waqas; Ali, Sajjad; Kashif, Syed Muhammad; Rahim, Fazal; Salar, Uzma; Khan, Khalid Mohammed

2016-04-01

6-Chloro-2-Aryl-1H-imidazo[4,5-b]pyridine derivatives 1-26 were synthesized and characterized by various spectroscopic techniques. All these derivatives were evaluated for their antiglycation, antioxidant and β-glucuronidase potential followed their docking studies. In antiglycation assay, compound 2 (IC50=240.10±2.50μM) and 4 (IC50=240.30±2.90μM) was found to be most active compound of this series, while compounds 3 (IC50=260.10±2.50μM), 6 (IC50=290.60±3.60μM), 13 (IC50=288.20±3.00μM) and 26 (IC50=292.10±3.20μM) also showed better activities than the standard rutin (IC50=294.50±1.50μM). In antioxidant assay, compound 1 (IC50=69.45±0.25μM), 2 (IC50=58.10±2.50μM), 3 (IC50=74.25±1.10μM), and 4 (IC50=72.50±3.30μM) showed good activities. In β-glucuronidase activity, compounds 3 (IC50=29.25±0.50μM), compound 1 (IC50=30.10±0.60μM) and compound 4 (IC50=46.10±1.10μM) showed a significant activity as compared to than standard D-Saccharic acid 1,4-lactonec (IC50=48.50±1.25μM) and their interaction with the enzyme was confirm by docking studies. Copyright © 2016 Elsevier Inc. All rights reserved.

Dry dock no. 4. Service Building between dry docks 4 ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Dry dock no. 4. Service Building between dry docks 4 and 5. Floor plans (Navy Yard Public Works Office 1941). In files of Cushman & Wakefield, building 501. Philadelphia Naval Business Center. - Naval Base Philadelphia-Philadelphia Naval Shipyard, Service Building, Dry Docks No. 4 & 5, League Island, Philadelphia, Philadelphia County, PA

CABS-dock web server for the flexible docking of peptides to proteins without prior knowledge of the binding site

PubMed Central

Kurcinski, Mateusz; Jamroz, Michal; Blaszczyk, Maciej; Kolinski, Andrzej; Kmiecik, Sebastian

2015-01-01

Protein–peptide interactions play a key role in cell functions. Their structural characterization, though challenging, is important for the discovery of new drugs. The CABS-dock web server provides an interface for modeling protein–peptide interactions using a highly efficient protocol for the flexible docking of peptides to proteins. While other docking algorithms require pre-defined localization of the binding site, CABS-dock does not require such knowledge. Given a protein receptor structure and a peptide sequence (and starting from random conformations and positions of the peptide), CABS-dock performs simulation search for the binding site allowing for full flexibility of the peptide and small fluctuations of the receptor backbone. This protocol was extensively tested over the largest dataset of non-redundant protein–peptide interactions available to date (including bound and unbound docking cases). For over 80% of bound and unbound dataset cases, we obtained models with high or medium accuracy (sufficient for practical applications). Additionally, as optional features, CABS-dock can exclude user-selected binding modes from docking search or to increase the level of flexibility for chosen receptor fragments. CABS-dock is freely available as a web server at http://biocomp.chem.uw.edu.pl/CABSdock. PMID:25943545

Protein-Protein Docking with F2Dock 2.0 and GB-Rerank

PubMed Central

Chowdhury, Rezaul; Rasheed, Muhibur; Keidel, Donald; Moussalem, Maysam; Olson, Arthur; Sanner, Michel; Bajaj, Chandrajit

2013-01-01

Motivation Computational simulation of protein-protein docking can expedite the process of molecular modeling and drug discovery. This paper reports on our new F2 Dock protocol which improves the state of the art in initial stage rigid body exhaustive docking search, scoring and ranking by introducing improvements in the shape-complementarity and electrostatics affinity functions, a new knowledge-based interface propensity term with FFT formulation, a set of novel knowledge-based filters and finally a solvation energy (GBSA) based reranking technique. Our algorithms are based on highly efficient data structures including the dynamic packing grids and octrees which significantly speed up the computations and also provide guaranteed bounds on approximation error. Results The improved affinity functions show superior performance compared to their traditional counterparts in finding correct docking poses at higher ranks. We found that the new filters and the GBSA based reranking individually and in combination significantly improve the accuracy of docking predictions with only minor increase in computation time. We compared F2 Dock 2.0 with ZDock 3.0.2 and found improvements over it, specifically among 176 complexes in ZLab Benchmark 4.0, F2 Dock 2.0 finds a near-native solution as the top prediction for 22 complexes; where ZDock 3.0.2 does so for 13 complexes. F2 Dock 2.0 finds a near-native solution within the top 1000 predictions for 106 complexes as opposed to 104 complexes for ZDock 3.0.2. However, there are 17 and 15 complexes where F2 Dock 2.0 finds a solution but ZDock 3.0.2 does not and vice versa; which indicates that the two docking protocols can also complement each other. Availability The docking protocol has been implemented as a server with a graphical client (TexMol) which allows the user to manage multiple docking jobs, and visualize the docked poses and interfaces. Both the server and client are available for download. Server: http://www.cs.utexas.edu/~bajaj/cvc/software/f2dock.shtml. Client: http://www.cs.utexas.edu/~bajaj/cvc/software/f2dockclient.shtml. PMID:23483883

On Docking, Scoring and Assessing Protein-DNA Complexes in a Rigid-Body Framework

PubMed Central

Parisien, Marc; Freed, Karl F.; Sosnick, Tobin R.

2012-01-01

We consider the identification of interacting protein-nucleic acid partners using the rigid body docking method FTdock, which is systematic and exhaustive in the exploration of docking conformations. The accuracy of rigid body docking methods is tested using known protein-DNA complexes for which the docked and undocked structures are both available. Additional tests with large decoy sets probe the efficacy of two published statistically derived scoring functions that contain a huge number of parameters. In contrast, we demonstrate that state-of-the-art machine learning techniques can enormously reduce the number of parameters required, thereby identifying the relevant docking features using a miniscule fraction of the number of parameters in the prior works. The present machine learning study considers a 300 dimensional vector (dependent on only 15 parameters), termed the Chemical Context Profile (CCP), where each dimension reflects a specific type of protein amino acid-nucleic acid base interaction. The CCP is designed to capture the chemical complementarities of the interface and is well suited for machine learning techniques. Our objective function is the Chemical Context Discrepancy (CCD), which is defined as the angle between the native system's CCP vector and the decoy's vector and which serves as a substitute for the more commonly used root mean squared deviation (RMSD). We demonstrate that the CCP provides a useful scoring function when certain dimensions are properly weighted. Finally, we explore how the amino acids on a protein's surface can help guide DNA binding, first through long-range interactions, followed by direct contacts, according to specific preferences for either the major or minor grooves of the DNA. PMID:22393431

Summary Report of Mission Acceleration Measurements for STS-79. Launched 16 Sep. 1996

NASA Technical Reports Server (NTRS)

Rogers, Melissa J. B.; Moskowitz, Milton E.; Hrovat, Kenneth; Reckart, Timothy A.

1997-01-01

The Space Acceleration Measurement System (SAMS) collected acceleration data in support of the Mechanics of Granular Materials experiment during the STS-79 Mir docking mission, September 1996. STS-79 was the first opportunity to record SAMS data on an Orbiter while it was docked to Mir. Crew exercise activities in the Atlantis middeck and the Mir base module are apparent in the data. The acceleration signals related to the Enhanced Orbiter Refrigerator Freezer had different characteristics when comparing the data recorded on Atlantis on STS-79 with the data recorded on Mir during STS-74. This is probably due, at least in part, to different transmission paths and SAMS sensor head mounting mechanisms. Data collected on Atlantis during the STS-79 docking indicate that accelerations due to vehicle and solar array structural modes from Mir transfer to Atlantis and that the structural modes of the Atlantis-Mir complex are different from those of either vehicle independently. A 0.18 Hz component of the SAMS data, present while the two vehicles were docked, was probably caused by the Mir solar arrays. Compared to Atlantis structural modes of about 3.9 and 4.9 Hz, the Atlantis-Mir complex has structural components of about 4.5 and 5.1 Hz. After docking, apparent structural modes appeared in the data at about 0.8 and 1.8 Hz. The appearance, disappearance, and change in the structural modes during the docking and undocking phases of the joint Atlantis-Mir operations indicates that the structural modes of the two spacecraft have an effect on the microgravity environment of each other. The transfer of structural and equipment related accelerations between vehicles is something that should be considered in the International Space Station era.

Autonomous Vision-Based Tethered-Assisted Rover Docking

NASA Technical Reports Server (NTRS)

Tsai, Dorian; Nesnas, Issa A.D.; Zarzhitsky, Dimitri

2013-01-01

Many intriguing science discoveries on planetary surfaces, such as the seasonal flows on crater walls and skylight entrances to lava tubes, are at sites that are currently inaccessible to state-of-the-art rovers. The in situ exploration of such sites is likely to require a tethered platform both for mechanical support and for providing power and communication. Mother/daughter architectures have been investigated where a mother deploys a tethered daughter into extreme terrains. Deploying and retracting a tethered daughter requires undocking and re-docking of the daughter to the mother, with the latter being the challenging part. In this paper, we describe a vision-based tether-assisted algorithm for the autonomous re-docking of a daughter to its mother following an extreme terrain excursion. The algorithm uses fiducials mounted on the mother to improve the reliability and accuracy of estimating the pose of the mother relative to the daughter. The tether that is anchored by the mother helps the docking process and increases the system's tolerance to pose uncertainties by mechanically aligning the mating parts in the final docking phase. A preliminary version of the algorithm was developed and field-tested on the Axel rover in the JPL Mars Yard. The algorithm achieved an 80% success rate in 40 experiments in both firm and loose soils and starting from up to 6 m away at up to 40 deg radial angle and 20 deg relative heading. The algorithm does not rely on an initial estimate of the relative pose. The preliminary results are promising and help retire the risk associated with the autonomous docking process enabling consideration in future martian and lunar missions.

241. BUILDINGS 455, 456, 509, 510 AND 457 (CELESTIAL NAVIGATION ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

241. BUILDINGS 455, 456, 509, 510 AND 457 (CELESTIAL NAVIGATION COMPLEX), 1942-43. BUREAU OF YARDS AND DOCKS STANDARD PLANS. VIEW NORTH ACROSS WASP ST. SHOWING THE 4 TRAINING SILOS FROM LEFT TO RIGHT: BUILDINGS 455, 456, 509, AND 510; AND, BESIDE THEM, BUILDING 457. - Quonset Point Naval Air Station, Roger Williams Way, North Kingstown, Washington County, RI

AnchorDock: Blind and Flexible Anchor-Driven Peptide Docking.

PubMed

Ben-Shimon, Avraham; Niv, Masha Y

2015-05-05

The huge conformational space stemming from the inherent flexibility of peptides is among the main obstacles to successful and efficient computational modeling of protein-peptide interactions. Current peptide docking methods typically overcome this challenge using prior knowledge from the structure of the complex. Here we introduce AnchorDock, a peptide docking approach, which automatically targets the docking search to the most relevant parts of the conformational space. This is done by precomputing the free peptide's structure and by computationally identifying anchoring spots on the protein surface. Next, a free peptide conformation undergoes anchor-driven simulated annealing molecular dynamics simulations around the predicted anchoring spots. In the challenging task of a completely blind docking test, AnchorDock produced exceptionally good results (backbone root-mean-square deviation ≤ 2.2Å, rank ≤15) for 10 of 13 unbound cases tested. The impressive performance of AnchorDock supports a molecular recognition pathway that is driven via pre-existing local structural elements. Copyright © 2015 Elsevier Ltd. All rights reserved.

Protein-protein docking with binding site patch prediction and network-based terms enhanced combinatorial scoring.

PubMed

Gong, Xinqi; Wang, Panwen; Yang, Feng; Chang, Shan; Liu, Bin; He, Hongqiu; Cao, Libin; Xu, Xianjin; Li, Chunhua; Chen, Weizu; Wang, Cunxin

2010-11-15

Protein-protein docking has made much progress in recent years, but challenges still exist. Here we present the application of our docking approach HoDock in CAPRI. In this approach, a binding site prediction is implemented to reduce docking sampling space and filter out unreasonable docked structures, and a network-based enhanced combinatorial scoring function HPNCscore is used to evaluate the decoys. The experimental information was combined with the predicted binding site to pick out the most likely key binding site residues. We applied the HoDock method in the recent rounds of the CAPRI experiments, and got good results as predictors on targets 39, 40, and 41. We also got good results as scorers on targets 35, 37, 40, and 41. This indicates that our docking approach can contribute to the progress of protein-protein docking methods and to the understanding of the mechanism of protein-protein interactions. © 2010 Wiley-Liss, Inc.

Insight into the reactive properties of newly synthesized 1,2,4-triazole derivative by combined experimental (FT-IR and FR-Raman) and theoretical (DFT and MD) study

NASA Astrophysics Data System (ADS)

Mary, Y. Sheena; Al-Omary, Fatmah A. M.; Mostafa, Gamal A. E.; El-Emam, Ali A.; Manjula, P. S.; Sarojini, B. K.; Narayana, B.; Armaković, Stevan; Armaković, Sanja J.; Van Alsenoy, C.

2017-08-01

The vibrational spectral analysis has been carried out on 4-[(E)-(4-hydroxybenzylidene)amino]-3-methyl-1H-1,2,4-triazole-5(4H)-thione (HBAMTT) in order explore the chemical and pharmacological properties. The most important reactive sites have been identified employing molecular electrostatic potential map. Nonlinear optical properties are identified and the first hyperpolarizability is 80.35 times that of urea, which is standard NLO material. The molecular activity is studied from the dislocation of the frontier molecular orbitals and NBO analysis is carried to gain an insight into the charge transfer within the molecular system. Using molecular electrostatic potential map, the electrophilic and nucleophilic sites are identified. Title molecule was further investigated from the aspect of local reactivity properties by calculations of average local ionization energies (ALIE) and Fukui functions. Vulnerability towards autoxidation and hydrolysis mechanisms has been assessed thanks to the calculations of bond dissociation energies (BDE) and radial distribution functions (RDF), respectively. This information was also valuable for the initial investigation of degradation properties of the title molecule. Thanks to the molecular docking studies, it can be concluded that docked ligand forms a stable complex with AChE and could be used as a new drug for the Alzheimer's disease, myasthenia gravis and glaucoma.

Synthesis, molecular docking and biological evaluation of novel 6-(4-(4-aminophenylsulfonyl)phenylamino)-5H-benzo[a]phenothiazin-5-one derivatives

NASA Astrophysics Data System (ADS)

Ravichandiran, Palanisamy; Athinarayanan, Jegan; Premnath, Dhanaraj; Periasamy, Vaiyapuri Subbarayan; Alshatwi, Ali A.; Vasanthkumar, Samuel

2015-03-01

A novel series of 6-(4-(4-aminophenylsulfonyl)phenylamino)-5H-benzo[a]phenothiazin-5-one derivatives have been synthesized and examined for their in vitro antibacterial activity against a panel of Gram-positive and Gram-negative bacteria. Among these, N-(4-(4-(5-oxo-5H-benzo[a]phenothiazin-6-ylamino)phenylsulfonyl)phenyl)-3,5-bis(trifluoromethyl)benzamide (3n) (0.4 μg/mL) and 4-ethyl-N-(4-(4-(5-oxo-5H-benzo[a]phenothiazin-6-ylamino)phenylsulfonyl)phenyl)benzamide (3l) (0.6 μg/mL) systems exhibited a potent inhibitory activity against Gram-positive organism Bacillus subtilis, when compare to the other synthesized compounds. Sparfloxacin (9.76 μg/mL), Norfloxacin (no activity) were employed as the standard drugs. An evaluation of the cytotoxicity of the title compounds (1, 2, 3a-n) revealed that they displayed low toxicity (26-115 mg/L) against cervical cancer cell line (SiHa). The results of these studies suggest that, phenothiazin-5-one derivatives are interesting binding agents for the development of new Gram-positive and Gram-negative antibacterial agents. To understand the interactions with protein receptors, docking simulation was done with crystal structures of B.subtilis (YmaH) and histone deacetylase (HDAC8) to determine the probable binding conformation.

Virgil Gus Grissom's Visit to LaRC

NASA Image and Video Library

1963-02-22

Astronaut Virgil "Gus" Grissom at the controls of the Visual Docking Simulator. From A.W. Vogeley, "Piloted Space-Flight Simulation at Langley Research Center," Paper presented at the American Society of Mechanical Engineers 1966 Winter Meeting, New York, NY, November 27-December 1, 1966. "This facility was [later known as the Visual-Optical Simulator.] It presents to the pilot an out-the-window view of his target in correct 6 degrees of freedom motion. The scene is obtained by a television camera pick-up viewing a small-scale gimbaled model of the target." "For docking studies, the docking target picture was projected onto the surface of a 20-foot-diameter sphere and the pilot could, effectively, maneuver into contract. this facility was used in a comparison study with the Rendezvous Docking Simulator - one of the few comparison experiments in which conditions were carefully controlled and a reasonable sample of pilots used. All pilots preferred the more realistic RDS visual scene. The pilots generally liked the RDS angular motion cues although some objected to the false gravity cues that these motions introduced. Training time was shorter on the RDS, but final performance on both simulators was essentially equal. " "For station-keeping studies, since close approach is not required, the target was presented to the pilot through a virtual-image system which projects his view to infinity, providing a more realistic effect. In addition to the target, the system also projects a star and horizon background. "

Pathfinder autonomous rendezvous and docking project

NASA Technical Reports Server (NTRS)

Lamkin, Stephen (Editor); Mccandless, Wayne (Editor)

1990-01-01

Capabilities are being developed and demonstrated to support manned and unmanned vehicle operations in lunar and planetary orbits. In this initial phase, primary emphasis is placed on definition of the system requirements for candidate Pathfinder mission applications and correlation of these system-level requirements with specific requirements. The FY-89 activities detailed are best characterized as foundation building. The majority of the efforts were dedicated to assessing the current state of the art, identifying desired elaborations and expansions to this level of development and charting a course that will realize the desired objectives in the future. Efforts are detailed across all work packages in developing those requirements and tools needed to test, refine, and validate basic autonomous rendezvous and docking elements.

Detailed analysis of grid-based molecular docking: A case study of CDOCKER-A CHARMm-based MD docking algorithm.

PubMed

Wu, Guosheng; Robertson, Daniel H; Brooks, Charles L; Vieth, Michal

2003-10-01

The influence of various factors on the accuracy of protein-ligand docking is examined. The factors investigated include the role of a grid representation of protein-ligand interactions, the initial ligand conformation and orientation, the sampling rate of the energy hyper-surface, and the final minimization. A representative docking method is used to study these factors, namely, CDOCKER, a molecular dynamics (MD) simulated-annealing-based algorithm. A major emphasis in these studies is to compare the relative performance and accuracy of various grid-based approximations to explicit all-atom force field calculations. In these docking studies, the protein is kept rigid while the ligands are treated as fully flexible and a final minimization step is used to refine the docked poses. A docking success rate of 74% is observed when an explicit all-atom representation of the protein (full force field) is used, while a lower accuracy of 66-76% is observed for grid-based methods. All docking experiments considered a 41-member protein-ligand validation set. A significant improvement in accuracy (76 vs. 66%) for the grid-based docking is achieved if the explicit all-atom force field is used in a final minimization step to refine the docking poses. Statistical analysis shows that even lower-accuracy grid-based energy representations can be effectively used when followed with full force field minimization. The results of these grid-based protocols are statistically indistinguishable from the detailed atomic dockings and provide up to a sixfold reduction in computation time. For the test case examined here, improving the docking accuracy did not necessarily enhance the ability to estimate binding affinities using the docked structures. Copyright 2003 Wiley Periodicals, Inc.

Multi-Sensor Testing for Automated Rendezvous and Docking Sensor Testing at the Flight Robotics Laboratory

NASA Technical Reports Server (NTRS)

Brewster, L.; Johnston, A.; Howard, R.; Mitchell, J.; Cryan, S.

2007-01-01

The Exploration Systems Architecture defines missions that require rendezvous, proximity operations, and docking (RPOD) of two spacecraft both in Low Earth Orbit (LEO) and in Low Lunar Orbit (LLO). Uncrewed spacecraft must perform automated and/or autonomous rendezvous, proximity operations and docking operations (commonly known as AR&D). The crewed missions may also perform rendezvous and docking operations and may require different levels of automation and/or autonomy, and must provide the crew with relative navigation information for manual piloting. The capabilities of the RPOD sensors are critical to the success of the Exploration Program. NASA has the responsibility to determine whether the Crew Exploration Vehicle (CEV) contractor proposed relative navigation sensor suite will meet the requirements. The relatively low technology readiness level of AR&D relative navigation sensors has been carried as one of the CEV Project's top risks. The AR&D Sensor Technology Project seeks to reduce the risk by the testing and analysis of selected relative navigation sensor technologies through hardware-in-the-loop testing and simulation. These activities will provide the CEV Project information to assess the relative navigation sensors maturity as well as demonstrate test methods and capabilities. The first year of this project focused on a series of"pathfinder" testing tasks to develop the test plans, test facility requirements, trajectories, math model architecture, simulation platform, and processes that will be used to evaluate the Contractor-proposed sensors. Four candidate sensors were used in the first phase of the testing. The second phase of testing used four sensors simultaneously: two Marshall Space Flight Center (MSFC) Advanced Video Guidance Sensors (AVGS), a laser-based video sensor that uses retroreflectors attached to the target vehicle, and two commercial laser range finders. The multi-sensor testing was conducted at MSFC's Flight Robotics Laboratory (FRL) using the FRL's 6-DOF gantry system, called the Dynamic Overhead Target System (DOTS). The target vehicle for "docking" in the laboratory was a mockup that was representative of the proposed CEV docking system, with added retroreflectors for the AVGS. The multi-sensor test configuration used 35 open-loop test trajectories covering three major objectives: (1) sensor characterization trajectories designed to test a wide range of performance parameters; (2) CEV-specific trajectories designed to test performance during CEV-like approach and departure profiles; and (3) sensor characterization tests designed for evaluating sensor performance under more extreme conditions as might be induced during a spacecraft failure or during contingency situations. This paper describes the test development, test facility, test preparations, test execution, and test results of the multi-sensor series of trajectories.

Evolution of the IBDM Structural Latch Development into a Generic Simplified Design

NASA Technical Reports Server (NTRS)

DeVriendt, K.; Dittmer, H.; Vrancken, D.; Urmston, P.; Gracia, O.

2010-01-01

This paper presents the evolution in the development of the structural latch for the International Berthing Docking Mechanism (IBDM, see Figure 1). It reports on the lessons learned since completion of the test program on the engineering development unit of the first generation latching system in 2007. The initial latch design has been through a second generation concept in 2008, and now evolved into a third generation of this mechanism. Functional and structural testing on the latest latch hardware has recently been completed with good results. The IBDM latching system will provide the structural connection between two mated space vehicles after berthing or docking. The mechanism guarantees that the interface seals become compressed to form a leak-tight pressure system that creates a passageway for the astronauts.

13. ORE DOCK, LOOKING EAST FROM HULETT NO. 1. WHEN ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

13. ORE DOCK, LOOKING EAST FROM HULETT NO. 1. WHEN BUILT IN 1911-1912, THIS WAS THE LARGEST ORE-UNLOADING DOCK ON THE GREAT LAKES. THE DOCK FEATURED FOUR HULETT UNLOADERS, EACH WITH A BUCKET CAPACITY OF 17 TONS; A 15-TON CAPACITY ORE STOCKING AND REHANDLING BRIDGE; AND A ONE-MILLION-TON CAPACITY ORE STORAGE YARD. THE WILLIAM-SEAVER-MORGAN COMPANY OF CLEVELAND BUILT THE DOCK EQUIPMENT. - Pennsylvania Railway Ore Dock, Lake Erie at Whiskey Island, approximately 1.5 miles west of Public Square, Cleveland, Cuyahoga County, OH

Docking of small molecules to farnesoid X receptors using AutoDock Vina with the Convex-PL potential: lessons learned from D3R Grand Challenge 2

NASA Astrophysics Data System (ADS)

Kadukova, Maria; Grudinin, Sergei

2018-01-01

The 2016 D3R Grand Challenge 2 provided an opportunity to test multiple protein-ligand docking protocols on a set of ligands bound to farnesoid X receptor that has many available experimental structures. We participated in the Stage 1 of the Challenge devoted to the docking pose predictions, with the mean RMSD value of our submission poses of 2.9 Å. Here we present a thorough analysis of our docking predictions made with AutoDock Vina and the Convex-PL rescoring potential by reproducing our submission protocol and running a series of additional molecular docking experiments. We conclude that a correct receptor structure, or more precisely, the structure of the binding pocket, plays the crucial role in the success of our docking studies. We have also noticed the important role of a local ligand geometry, which seems to be not well discussed in literature. We succeed to improve our results up to the mean RMSD value of 2.15-2.33 Å dependent on the models of the ligands, if docking these to all available homologous receptors. Overall, for docking of ligands of diverse chemical series we suggest to perform docking of each of the ligands to a set of multiple receptors that are homologous to the target.

CABS-dock web server for the flexible docking of peptides to proteins without prior knowledge of the binding site.

PubMed

Kurcinski, Mateusz; Jamroz, Michal; Blaszczyk, Maciej; Kolinski, Andrzej; Kmiecik, Sebastian

2015-07-01

Protein-peptide interactions play a key role in cell functions. Their structural characterization, though challenging, is important for the discovery of new drugs. The CABS-dock web server provides an interface for modeling protein-peptide interactions using a highly efficient protocol for the flexible docking of peptides to proteins. While other docking algorithms require pre-defined localization of the binding site, CABS-dock does not require such knowledge. Given a protein receptor structure and a peptide sequence (and starting from random conformations and positions of the peptide), CABS-dock performs simulation search for the binding site allowing for full flexibility of the peptide and small fluctuations of the receptor backbone. This protocol was extensively tested over the largest dataset of non-redundant protein-peptide interactions available to date (including bound and unbound docking cases). For over 80% of bound and unbound dataset cases, we obtained models with high or medium accuracy (sufficient for practical applications). Additionally, as optional features, CABS-dock can exclude user-selected binding modes from docking search or to increase the level of flexibility for chosen receptor fragments. CABS-dock is freely available as a web server at http://biocomp.chem.uw.edu.pl/CABSdock. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

The SH2/SH3 adaptor protein dock interacts with the Ste20-like kinase misshapen in controlling growth cone motility.

PubMed

Ruan, W; Pang, P; Rao, Y

1999-11-01

Recent studies suggest that the SH2/SH3 adaptor Dock/Nck transduces tyrosine phosphorylation signals to the actin cytoskeleton in regulating growth cone motility. The signaling cascade linking the action of Dock/Nck to the reorganization of cytoskeleton is poorly understood. We now demonstrate that Dock interacts with the Ste20-like kinase Misshapen (Msn) in the Drosophila photoreceptor (R cell) growth cones. Loss of msn causes a failure of growth cones to stop at the target, a phenotype similar to loss of dock, whereas overexpression of msn induces pretarget growth cone termination. Physical and genetic interactions between Msn and Dock indicate a role for Msn in the Dock signaling pathway. We propose that Msn functions as a key controller of growth cone cytoskeleton in response to Dock-mediated signals.

Mono-oxime bisquaternary acetylcholinesterase reactivators with prop-1,3-diyl linkage-Preparation, in vitro screening and molecular docking.

PubMed

Musilek, Kamil; Komloova, Marketa; Holas, Ondrej; Horova, Anna; Pohanka, Miroslav; Gunn-Moore, Frank; Dohnal, Vlastimil; Dolezal, Martin; Kuca, Kamil

2011-01-15

The treatment of organophosphorus (OP) poisoning consists of the administration of a parasympatholytic agent (e.g., atropine), an anticonvulsant (e.g., diazepam) and an acetylcholinesterase (AChE) reactivator (e.g., obidoxime). The AChE reactivator is the causal treatment of OP exposure, because it cleaves the OP moiety covalently bound to the AChE active site. In this paper, fourteen novel AChE reactivators are described. Their design originated from a former promising compound K027. These compounds were synthesized, evaluated in vitro on human AChE (hAChE) inhibited by tabun, paraoxon, methylparaoxon and DFP and then compared to commercial hAChE reactivators (pralidoxime, HI-6, trimedoxime, obidoxime, methoxime) or previously prepared compounds (K027, K203). Three of these novel compounds showed a promising ability to reactivate hAChE comparable or better than the used standards. Consequently, a molecular docking study was performed for three of these promising novel compounds. The docking results confirmed the apparent influence of π-π or cation-π interactions and hydrogen bonding for reactivator binding within the hAChE active site cleft. The SAR features concerning the non-oxime part of the reactivator molecule are also discussed. Copyright © 2010 Elsevier Ltd. All rights reserved.

In vitro cytotoxic and in silico activity of piperine isolated from Piper nigrum fruits Linn.

PubMed

Paarakh, Padmaa M; Sreeram, Dileep Chandra; D, Shruthi S; Ganapathy, Sujan P S

2015-12-01

Piper nigrum [Piperaceae], commonly known as black pepper is used as medicine fairly throughout the greater part of India and as a spice globally. To isolate piperine and evaluate in vitro cytotoxic [antiproliferative] activity and in silico method. Piperine was isolated from the fruits of P.nigrum. Piperine was characterized by UV,IR, (1)H-NMR, (13)C-NMR and Mass spectrum. Standardization of piperine was done also by HPTLC fingerprinting. In vitro cytotoxic activity was done using HeLa cell lines by MTT assay at different concentrations ranging from 20 to 100 μg/ml in triplicate and in silico docking studies using enzyme EGFR tyrosine kinase. Fingerprinting of isolated piperine were done by HPTLC method. The IC50 value was found to be 61.94 ± 0.054 μg/ml in in vitro cytotoxic activity in HeLa Cell lines. Piperine was subjected to molecular docking studies for the inhibition of the enzyme EGFR tyrosine kinase, which is one of the targets for inhibition of cancer cells. It has shown -7.6 kJ mol(-1) binding and 7.06 kJ mol(-1) docking energy with two hydrogen bonds. piperine has shown to possess in vitro cytotoxic activity and in silico studies.

Comparison of neural histomorphology in tail tips from pigs docked using clippers or cautery iron.

PubMed

Kells, N J; Beausoleil, N J; Johnson, C B; Sutherland, M A; Morrison, R S; Roe, W

2017-07-01

Tail docking of pigs is commonly performed to reduce the incidence of unwanted tail-biting behaviour. Two docking methods are commonly used: blunt trauma cutting (i.e. using side clippers), or cutting and concurrent cauterisation using a hot cautery iron. A potential consequence of tail amputation is the development of neuromas at the docking site. Neuromas have been linked to neuropathic pain, which can influence the longer-term welfare of affected individuals. To determine whether method of tail docking influences the extent of neuroma formation, 75 pigs were allocated to one of three treatments at birth: tail docked using clippers; tail docked using cautery iron; tail left intact. Tail docking was performed at 2 days of age and pigs were kept under conventional conditions until slaughter at 21 weeks of age. Tails were removed following slaughter and subjected to histological examination. Nerve histomorphology was scored according to the following scale: 1=discrete well-organised nerve bundles; 2=moderate neural proliferation and disorganisation affecting more than half of the circumference of the tail; 3=marked neural proliferation to form almost continuous disorganised bundles or non-continuous enlarged bundles compressing the surrounding connective tissue. Scores of 2 or 3 indicated neuroma formation. Scores were higher in docked pigs than undocked pigs (P<0.001), but did not differ between pigs docked using clippers and those docked using cautery (P=0.23). The results indicate that tail docking using either clippers or cautery results in neuroma formation, thus having the potential to affect long-term pig welfare.

Human and Server Docking Prediction for CAPRI Round 30–35 Using LZerD with Combined Scoring Functions

PubMed Central

Peterson, Lenna X.; Kim, Hyungrae; Esquivel-Rodriguez, Juan; Roy, Amitava; Han, Xusi; Shin, Woong-Hee; Zhang, Jian; Terashi, Genki; Lee, Matt; Kihara, Daisuke

2016-01-01

We report the performance of protein-protein docking predictions by our group for recent rounds of the Critical Assessment of Prediction of Interactions (CAPRI), a community-wide assessment of state-of-the-art docking methods. Our prediction procedure uses a protein-protein docking program named LZerD developed in our group. LZerD represents a protein surface with 3D Zernike descriptors (3DZD), which are based on a mathematical series expansion of a 3D function. The appropriate soft representation of protein surface with 3DZD makes the method more tolerant to conformational change of proteins upon docking, which adds an advantage for unbound docking. Docking was guided by interface residue prediction performed with BindML and cons-PPISP as well as literature information when available. The generated docking models were ranked by a combination of scoring functions, including PRESCO, which evaluates the native-likeness of residues’ spatial environments in structure models. First, we discuss the overall performance of our group in the CAPRI prediction rounds and investigate the reasons for unsuccessful cases. Then, we examine the performance of several knowledge-based scoring functions and their combinations for ranking docking models. It was found that the quality of a pool of docking models generated by LZerD, i.e. whether or not the pool includes near-native models, can be predicted by the correlation of multiple scores. Although the current analysis used docking models generated by LZerD, findings on scoring functions are expected to be universally applicable to other docking methods. PMID:27654025

Structural insights into transient receptor potential vanilloid type 1 (TRPV1) from homology modeling, flexible docking, and mutational studies.

PubMed

Lee, Jin Hee; Lee, Yoonji; Ryu, HyungChul; Kang, Dong Wook; Lee, Jeewoo; Lazar, Jozsef; Pearce, Larry V; Pavlyukovets, Vladimir A; Blumberg, Peter M; Choi, Sun

2011-04-01

The transient receptor potential vanilloid subtype 1 (TRPV1) is a non-selective cation channel composed of four monomers with six transmembrane helices (TM1-TM6). TRPV1 is found in the central and peripheral nervous system, and it is an important therapeutic target for pain relief. We describe here the construction of a tetrameric homology model of rat TRPV1 (rTRPV1). We experimentally evaluated by mutational analysis the contribution of residues of rTRPV1 contributing to ligand binding by the prototypical TRPV1 agonists, capsaicin and resiniferatoxin (RTX). We then performed docking analysis using our homology model. The docking results with capsaicin and RTX showed that our homology model was reliable, affording good agreement with our mutation data. Additionally, the binding mode of a simplified RTX (sRTX) ligand as predicted by the modeling agreed well with those of capsaicin and RTX, accounting for the high binding affinity of the sRTX ligand for TRPV1. Through the homology modeling, docking and mutational studies, we obtained important insights into the ligand-receptor interactions at the molecular level which should prove of value in the design of novel TRPV1 ligands.

Structural insights into transient receptor potential vanilloid type 1 (TRPV1) from homology modeling, flexible docking, and mutational studies

NASA Astrophysics Data System (ADS)

Lee, Jin Hee; Lee, Yoonji; Ryu, HyungChul; Kang, Dong Wook; Lee, Jeewoo; Lazar, Jozsef; Pearce, Larry V.; Pavlyukovets, Vladimir A.; Blumberg, Peter M.; Choi, Sun

2011-04-01

The transient receptor potential vanilloid subtype 1 (TRPV1) is a non-selective cation channel composed of four monomers with six transmembrane helices (TM1-TM6). TRPV1 is found in the central and peripheral nervous system, and it is an important therapeutic target for pain relief. We describe here the construction of a tetrameric homology model of rat TRPV1 (rTRPV1). We experimentally evaluated by mutational analysis the contribution of residues of rTRPV1 contributing to ligand binding by the prototypical TRPV1 agonists, capsaicin and resiniferatoxin (RTX). We then performed docking analysis using our homology model. The docking results with capsaicin and RTX showed that our homology model was reliable, affording good agreement with our mutation data. Additionally, the binding mode of a simplified RTX (sRTX) ligand as predicted by the modeling agreed well with those of capsaicin and RTX, accounting for the high binding affinity of the sRTX ligand for TRPV1. Through the homology modeling, docking and mutational studies, we obtained important insights into the ligand-receptor interactions at the molecular level which should prove of value in the design of novel TRPV1 ligands.

Combining self- and cross-docking as benchmark tools: the performance of DockBench in the D3R Grand Challenge 2

NASA Astrophysics Data System (ADS)

Salmaso, Veronica; Sturlese, Mattia; Cuzzolin, Alberto; Moro, Stefano

2018-01-01

Molecular docking is a powerful tool in the field of computer-aided molecular design. In particular, it is the technique of choice for the prediction of a ligand pose within its target binding site. A multitude of docking methods is available nowadays, whose performance may vary depending on the data set. Therefore, some non-trivial choices should be made before starting a docking simulation. In the same framework, the selection of the target structure to use could be challenging, since the number of available experimental structures is increasing. Both issues have been explored within this work. The pose prediction of a pool of 36 compounds provided by D3R Grand Challenge 2 organizers was preceded by a pipeline to choose the best protein/docking-method couple for each blind ligand. An integrated benchmark approach including ligand shape comparison and cross-docking evaluations was implemented inside our DockBench software. The results are encouraging and show that bringing attention to the choice of the docking simulation fundamental components improves the results of the binding mode predictions.

jMetalCpp: optimizing molecular docking problems with a C++ metaheuristic framework.

PubMed

López-Camacho, Esteban; García Godoy, María Jesús; Nebro, Antonio J; Aldana-Montes, José F

2014-02-01

Molecular docking is a method for structure-based drug design and structural molecular biology, which attempts to predict the position and orientation of a small molecule (ligand) in relation to a protein (receptor) to produce a stable complex with a minimum binding energy. One of the most widely used software packages for this purpose is AutoDock, which incorporates three metaheuristic techniques. We propose the integration of AutoDock with jMetalCpp, an optimization framework, thereby providing both single- and multi-objective algorithms that can be used to effectively solve docking problems. The resulting combination of AutoDock + jMetalCpp allows users of the former to easily use the metaheuristics provided by the latter. In this way, biologists have at their disposal a richer set of optimization techniques than those already provided in AutoDock. Moreover, designers of metaheuristic techniques can use molecular docking for case studies, which can lead to more efficient algorithms oriented to solving the target problems.  jMetalCpp software adapted to AutoDock is freely available as a C++ source code at http://khaos.uma.es/AutodockjMetal/.

SAMPL4 & DOCK3.7: lessons for automated docking procedures

NASA Astrophysics Data System (ADS)

Coleman, Ryan G.; Sterling, Teague; Weiss, Dahlia R.

2014-03-01

The SAMPL4 challenges were used to test current automated methods for solvation energy, virtual screening, pose and affinity prediction of the molecular docking pipeline DOCK 3.7. Additionally, first-order models of binding affinity were proposed as milestones for any method predicting binding affinity. Several important discoveries about the molecular docking software were made during the challenge: (1) Solvation energies of ligands were five-fold worse than any other method used in SAMPL4, including methods that were similarly fast, (2) HIV Integrase is a challenging target, but automated docking on the correct allosteric site performed well in terms of virtual screening and pose prediction (compared to other methods) but affinity prediction, as expected, was very poor, (3) Molecular docking grid sizes can be very important, serious errors were discovered with default settings that have been adjusted for all future work. Overall, lessons from SAMPL4 suggest many changes to molecular docking tools, not just DOCK 3.7, that could improve the state of the art. Future difficulties and projects will be discussed.

First Experiences with the New Senhance® Telerobotic System in Visceral Surgery.

PubMed

Stephan, Dietmar; Sälzer, Heike; Willeke, Frank

2018-02-01

Until recently, robotic-assisted surgery has exclusively been connected to the name DaVinci®. In 2016, a second robotic system, the Senhance®, became available. To introduce the new robotic system into clinical routine, detailed team training and an integration program were useful. Within the first 6 months, 116 cases were performed with this system. The integration program intended to start with simple and well-standardized clinical cases. We chose inguinal hernia repair using the TAPP (transabdominal preperitoneal) technique as the starting procedure. Subsequently, we added upper gastrointestinal surgery and cholecystectomies, and colorectal procedures have since also been included. Initial experience with the Senhance system as the first installation in Germany shows that it is suitable for surgery in general and for visceral surgery in particular. The application is safe due to the unproblematically quick changeover to normal laparoscopy and easy to integrate due to the very short system integration times (docking times). Since it is a laparoscopic-based system, following an integration program will enable experienced laparoscopic surgeons to very quickly manage more complex procedures. Due to lower costs, introducing robotic surgery starting with simple and standardized procedures is more feasible. After the establishment of this second robotic system, future studies will have to specifically look at differences in surgical results and basic conditions of different robotic-assisted systems. This paper documents the decision-making process of a hospital towards the integration of a robotic system and the selection criteria used while also demonstrating the planning and execution process during the introduction of the system into clinical routine.

Prediction of the binding sites of huperzine A in acetylcholinesterase by docking studies

NASA Astrophysics Data System (ADS)

Pang, Yuan-Ping; Kozikowski, Alan P.

1994-12-01

We have performed docking studies with the SYSDOC program on acetylcholinesterase (AChE) to predict the binding sites in AChE of huperzine A (HA), which is a potent and selective, reversible inhibitor of AChE. The unique aspects of our docking studies include the following: (i) Molecular flexibility of the guest and the host is taken into account, which permits both to change their conformations upon binding. (ii) The binding energy is evaluated by a sum of energies of steric, electrostatic and hydrogen bonding interactions. In the energy calculation no grid approximation is used, and all hydrogen atoms of the system are treated explicitly. (iii) The energy of cation-π interactions between the guest and the host, which is important in the binding of AChE, is included in the calculated binding energy. (iv) Docking is performed in all regions of the host's binding cavity. Based on our docking studies and the pharmacological results reported for HA and its analogs, we predict that HA binds to the bottom of the binding cavity of AChE (the gorge) with its ammonium group interacting with Trp84, Phe330, Glu199 and Asp72 (catalytic site). At the the opening of the gorge with its ammonium group partially interacting with Trp279 (peripheral site). At the catalytic site, three partially overlapping subsites of HA were identified which might provide a dynamic view of binding of HA to the catalytic site.

[Supercomputer investigation of the protein-ligand system low-energy minima].

PubMed

Oferkin, I V; Sulimov, A V; Katkova, E V; Kutov, D K; Grigoriev, F V; Kondakova, O A; Sulimov, V B

2015-01-01

The accuracy of the protein-ligand binding energy calculations and ligand positioning is strongly influenced by the choice of the docking target function. This work demonstrates the evaluation of the five different target functions used in docking: functions based on MMFF94 force field and functions based on PM7 quantum-chemical method accounting or without accounting the implicit solvent model (PCM, COSMO or SGB). For these purposes the ligand positions corresponding to the minima of the target function and the experimentally known ligand positions in the protein active site (crystal ligand positions) were compared. Each function was examined on the same test-set of 16 protein-ligand complexes. The new parallelized docking program FLM based on Monte Carlo search algorithm was developed to perform the comprehensive low-energy minima search and to calculate the protein-ligand binding energy. This study demonstrates that the docking target function based on the MMFF94 force field can be used to detect the crystal or near crystal positions of the ligand by the finding the low-energy local minima spectrum of the target function. The importance of solvent accounting in the docking process for the accurate ligand positioning is also shown. The accuracy of the ligand positioning as well as the correlation between the calculated and experimentally determined protein-ligand binding energies are improved when the MMFF94 force field is substituted by the new PM7 method with implicit solvent accounting.

Identification of a New Isoindole-2-yl Scaffold as a Qo and Qi Dual Inhibitor of Cytochrome bc 1 Complex: Virtual Screening, Synthesis, and Biochemical Assay.

PubMed

Azizian, Homa; Bagherzadeh, Kowsar; Shahbazi, Sophia; Sharifi, Niusha; Amanlou, Massoud

2017-09-18

Respiratory chain ubiquinol-cytochrome (cyt) c oxidoreductase (cyt bc 1 or complex III) has been demonstrated as a promising target for numerous antibiotics and fungicide applications. In this study, a virtual screening of NCI diversity database was carried out in order to find novel Qo/Qi cyt bc 1 complex inhibitors. Structure-based virtual screening and molecular docking methodology were employed to further screen compounds with inhibition activity against cyt bc 1 complex after extensive reliability validation protocol with cross-docking method and identification of the best score functions. Subsequently, the application of rational filtering procedure over the target database resulted in the elucidation of a novel class of cyt bc 1 complex potent inhibitors with comparable binding energies and biological activities to those of the standard inhibitor, antimycin.

Coding and quantification of a facial expression for pain in lambs.

PubMed

Guesgen, M J; Beausoleil, N J; Leach, M; Minot, E O; Stewart, M; Stafford, K J

2016-11-01

Facial expressions are routinely used to assess pain in humans, particularly those who are non-verbal. Recently, there has been an interest in developing coding systems for facial grimacing in non-human animals, such as rodents, rabbits, horses and sheep. The aims of this preliminary study were to: 1. Qualitatively identify facial feature changes in lambs experiencing pain as a result of tail-docking and compile these changes to create a Lamb Grimace Scale (LGS); 2. Determine whether human observers can use the LGS to differentiate tail-docked lambs from control lambs and differentiate lambs before and after docking; 3. Determine whether changes in facial action units of the LGS can be objectively quantified in lambs before and after docking; 4. Evaluate effects of restraint of lambs on observers' perceptions of pain using the LGS and on quantitative measures of facial action units. By comparing images of lambs before (no pain) and after (pain) tail-docking, the LGS was devised in consultation with scientists experienced in assessing facial expression in other species. The LGS consists of five facial action units: Orbital Tightening, Mouth Features, Nose Features, Cheek Flattening and Ear Posture. The aims of the study were addressed in two experiments. In Experiment I, still images of the faces of restrained lambs were taken from video footage before and after tail-docking (n=4) or sham tail-docking (n=3). These images were scored by a group of five naïve human observers using the LGS. Because lambs were restrained for the duration of the experiment, Ear Posture was not scored. The scores for the images were averaged to provide one value per feature per period and then scores for the four LGS action units were averaged to give one LGS score per lamb per period. In Experiment II, still images of the faces nine lambs were taken before and after tail-docking. Stills were taken when lambs were restrained and unrestrained in each period. A different group of five human observers scored the images from Experiment II. Changes in facial action units were also quantified objectively by a researcher using image measurement software. In both experiments LGS scores were analyzed using a linear MIXED model to evaluate the effects of tail docking on observers' perception of facial expression changes. Kendall's Index of Concordance was used to measure reliability among observers. In Experiment I, human observers were able to use the LGS to differentiate docked lambs from control lambs. LGS scores significantly increased from before to after treatment in docked lambs but not control lambs. In Experiment II there was a significant increase in LGS scores after docking. This was coupled with changes in other validated indicators of pain after docking in the form of pain-related behaviour. Only two components, Mouth Features and Orbital Tightening, showed significant quantitative changes after docking. The direction of these changes agree with the description of these facial action units in the LGS. Restraint affected people's perceptions of pain as well as quantitative measures of LGS components. Freely moving lambs were scored lower using the LGS over both periods and had a significantly smaller eye aperture and smaller nose and ear angles than when they were held. Agreement among observers for LGS scores were fair overall (Experiment I: W=0.60; Experiment II: W=0.66). This preliminary study demonstrates changes in lamb facial expression associated with pain. The results of these experiments should be interpreted with caution due to low lamb numbers. Copyright © 2016 Elsevier B.V. All rights reserved.

Modular, Reconfigurable, High-Energy Technology Development

NASA Technical Reports Server (NTRS)

Carrington, Connie; Howell, Joe

2006-01-01

The Modular, Reconfigurable High-Energy (MRHE) Technology Demonstrator project was to have been a series of ground-based demonstrations to mature critical technologies needed for in-space assembly of a highpower high-voltage modular spacecraft in low Earth orbit, enabling the development of future modular solar-powered exploration cargo-transport vehicles and infrastructure. MRHE was a project in the High Energy Space Systems (HESS) Program, within NASA's Exploration Systems Research and Technology (ESR&T) Program. NASA participants included Marshall Space Flight Center (MSFC), the Jet Propulsion Laboratory (JPL), and Glenn Research Center (GRC). Contractor participants were the Boeing Phantom Works in Huntsville, AL, Lockheed Martin Advanced Technology Center in Palo Alto, CA, ENTECH, Inc. in Keller, TX, and the University of AL Huntsville (UAH). MRHE's technical objectives were to mature: (a) lightweight, efficient, high-voltage, radiation-resistant solar power generation (SPG) technologies; (b) innovative, lightweight, efficient thermal management systems; (c) efficient, 100kW-class, high-voltage power delivery systems from an SPG to an electric thruster system; (d) autonomous rendezvous and docking technology for in-space assembly of modular, reconfigurable spacecraft; (e) robotic assembly of modular space systems; and (f) modular, reconfigurable distributed avionics technologies. Maturation of these technologies was to be implemented through a series of increasingly-inclusive laboratory demonstrations that would have integrated and demonstrated two systems-of-systems: (a) the autonomous rendezvous and docking of modular spacecraft with deployable structures, robotic assembly, reconfiguration both during assembly and (b) the development and integration of an advanced thermal heat pipe and a high-voltage power delivery system with a representative lightweight high-voltage SPG array. In addition, an integrated simulation testbed would have been developed containing software models representing the technologies being matured in the laboratory demos. The testbed would have also included models for non-MRHE developed subsystems such as electric propulsion, so that end-to-end performance could have been assessed. This paper presents an overview of the MRHE Phase I activities at MSFC and its contractor partners. One of the major Phase I accomplishments is the assembly demonstration in the Lockheed Martin Advanced Technology Center (LMATC) Robot-Satellite facility, in which three robot-satellites successfully demonstrated rendezvous & docking, self-assembly, reconfiguration, adaptable GN&C, deployment, and interfaces between modules. Phase I technology maturation results from ENTECH include material recommendations for radiation hardened Stretched Lens Array (SLA) concentrator lenses, and a design concept and test results for a hi-voltage PV receiver. UAH's accomplishments include Supertube heatpipe test results, which support estimates of thermal conductivities at 30,000 times that of an equivalent silver rod. MSFC performed systems trades and developed a preliminary concept design for a 100kW-class modular reconfigurable solar electric propulsion transport vehicle, and Boeing Phantom Works in Huntsville performed assembly and rendezvous and docking trades. A concept animation video was produced by SAIC, wllich showed rendezvous and docking and SLA-square-rigger deployment in LEO.

Experimental validation of docking and capture using space robotics testbeds

NASA Technical Reports Server (NTRS)

Spofford, John

1991-01-01

Docking concepts include capture, berthing, and docking. The definitions of these terms, consistent with AIAA, are as follows: (1) capture (grasping)--the use of a manipulator to make initial contact and attachment between transfer vehicle and a platform; (2) berthing--positioning of a transfer vehicle or payload into platform restraints using a manipulator; and (3) docking--propulsive mechanical connection between vehicle and platform. The combination of the capture and berthing operations is effectively the same as docking; i.e., capture (grasping) + berthing = docking. These concepts are discussed in terms of Martin Marietta's ability to develop validation methods using robotics testbeds.

Monte Carlo replica-exchange based ensemble docking of protein conformations.

PubMed

Zhang, Zhe; Ehmann, Uwe; Zacharias, Martin

2017-05-01

A replica-exchange Monte Carlo (REMC) ensemble docking approach has been developed that allows efficient exploration of protein-protein docking geometries. In addition to Monte Carlo steps in translation and orientation of binding partners, possible conformational changes upon binding are included based on Monte Carlo selection of protein conformations stored as ordered pregenerated conformational ensembles. The conformational ensembles of each binding partner protein were generated by three different approaches starting from the unbound partner protein structure with a range spanning a root mean square deviation of 1-2.5 Å with respect to the unbound structure. Because MC sampling is performed to select appropriate partner conformations on the fly the approach is not limited by the number of conformations in the ensemble compared to ensemble docking of each conformer pair in ensemble cross docking. Although only a fraction of generated conformers was in closer agreement with the bound structure the REMC ensemble docking approach achieved improved docking results compared to REMC docking with only the unbound partner structures or using docking energy minimization methods. The approach has significant potential for further improvement in combination with more realistic structural ensembles and better docking scoring functions. Proteins 2017; 85:924-937. © 2016 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

DOCKSCORE: a webserver for ranking protein-protein docked poses.

PubMed

Malhotra, Sony; Mathew, Oommen K; Sowdhamini, Ramanathan

2015-04-24

Proteins interact with a variety of other molecules such as nucleic acids, small molecules and other proteins inside the cell. Structure-determination of protein-protein complexes is challenging due to several reasons such as the large molecular weights of these macromolecular complexes, their dynamic nature, difficulty in purification and sample preparation. Computational docking permits an early understanding of the feasibility and mode of protein-protein interactions. However, docking algorithms propose a number of solutions and it is a challenging task to select the native or near native pose(s) from this pool. DockScore is an objective scoring scheme that can be used to rank protein-protein docked poses. It considers several interface parameters, namely, surface area, evolutionary conservation, hydrophobicity, short contacts and spatial clustering at the interface for scoring. We have implemented DockScore in form of a webserver for its use by the scientific community. DockScore webserver can be employed, subsequent to docking, to perform scoring of the docked solutions, starting from multiple poses as inputs. The results, on scores and ranks for all the poses, can be downloaded as a csv file and graphical view of the interface of best ranking poses is possible. The webserver for DockScore is made freely available for the scientific community at: http://caps.ncbs.res.in/dockscore/ .

Quick Attach Docking Interface for Lunar Electric Rover

NASA Technical Reports Server (NTRS)

Schuler, Jason M.; Nick, Andrew J.; Immer, Christopher; Mueller, Robert P.

2010-01-01

The NASA Lunar Electric Rover (LER) has been developed at Johnson Space Center as a next generation mobility platform. Based upon a twelve wheel omni-directional chassis with active suspension the LER introduces a number of novel capabilities for lunar exploration in both manned and unmanned scenarios. Besides being the primary vehicle for astronauts on the lunar surface, LER will perform tasks such as lunar regolith handling (to include dozing, grading, and excavation), equipment transport, and science operations. In an effort to support these additional tasks a team at the Kennedy Space Center has produced a universal attachment interface for LER known as the Quick Attach. The Quick Attach is a compact system that has been retro-fitted to the rear of the LER giving it the ability to dock and undock on the fly with various implements. The Quick Attach utilizes a two stage docking approach; the first is a mechanical mate which aligns and latches a passive set of hooks on an implement with an actuated cam surface on LER. The mechanical stage is tolerant to misalignment between the implement and the LER during docking and once the implement is captured a preload is applied to ensure a positive lock. The second stage is an umbilical connection which consists of a dust resistant enclosure housing a compliant mechanism that is optionally actuated to mate electrical and fluid connections for suitable implements. The Quick Attach system was designed with the largest foreseen input loads considered including excavation operations and large mass utility attachments. The Quick Attach system was demonstrated at the Desert Research And Technology Studies (D-RA TS) field test in Flagstaff, AZ along with the lightweight dozer blade LANCE. The LANCE blade is the first implement to utilize the Quick Attach interface and demonstrated the tolerance, speed, and strength of the system in a lunar analog environment.

Genetic dissection of TrkB activated signalling pathways required for specific aspects of the taste system

PubMed Central

2014-01-01

Background Neurotrophin-4 (NT-4) and brain derived neurotrophic factor (BDNF) bind to the same receptor, Ntrk2/TrkB, but play distinct roles in the development of the rodent gustatory system. However, the mechanisms underlying these processes are lacking. Results Here, we demonstrate, in vivo, that single or combined point mutations in major adaptor protein docking sites on TrkB receptor affect specific aspects of the mouse gustatory development, known to be dependent on BDNF or NT-4. In particular, mice with a mutation in the TrkB-SHC docking site had reduced gustatory neuron survival at both early and later stages of development, when survival is dependent on NT-4 and BDNF, respectively. In addition, lingual innervation and taste bud morphology, both BDNF-dependent functions, were altered in these mutants. In contrast, mutation of the TrkB-PLCγ docking site alone did not affect gustatory neuron survival. Moreover, innervation to the tongue was delayed in these mutants and taste receptor expression was altered. Conclusions We have genetically dissected pathways activated downstream of the TrkB receptor that are required for specific aspects of the taste system controlled by the two neurotrophins NT-4 and BDNF. In addition, our results indicate that TrkB also regulate the expression of specific taste receptors by distinct signalling pathways. These results advance our knowledge of the biology of the taste system, one of the fundamental sensory systems crucial for an organism to relate to the environment. PMID:25256039

Assessing the performance of MM/PBSA and MM/GBSA methods. 8. Predicting binding free energies and poses of protein-RNA complexes.

PubMed

Chen, Fu; Sun, Huiyong; Wang, Junmei; Zhu, Feng; Liu, Hui; Wang, Zhe; Lei, Tailong; Li, Youyong; Hou, Tingjun

2018-06-21

Molecular docking provides a computationally efficient way to predict the atomic structural details of protein-RNA interactions (PRI), but accurate prediction of the three-dimensional structures and binding affinities for PRI is still notoriously difficult, partly due to the unreliability of the existing scoring functions for PRI. MM/PBSA and MM/GBSA are more theoretically rigorous than most scoring functions for protein-RNA docking, but their prediction performance for protein-RNA systems remains unclear. Here, we systemically evaluated the capability of MM/PBSA and MM/GBSA to predict the binding affinities and recognize the near-native binding structures for protein-RNA systems with different solvent models and interior dielectric constants (ϵ in ). For predicting the binding affinities, the predictions given by MM/GBSA based on the minimized structures in explicit solvent and the GBGBn1 model with ϵ in = 2 yielded the highest correlation with the experimental data. Moreover, the MM/GBSA calculations based on the minimized structures in implicit solvent and the GBGBn1 model distinguished the near-native binding structures within the top 10 decoys for 118 out of the 149 protein-RNA systems (79.2%). This performance is better than all docking scoring functions studied here. Therefore, the MM/GBSA rescoring is an efficient way to improve the prediction capability of scoring functions for protein-RNA systems. Published by Cold Spring Harbor Laboratory Press for the RNA Society.

GEMINI-TITAN (GT)-10 - EARTH SKY - RENDEZVOUS - OUTER SPACE

NASA Image and Video Library

1966-07-18

S66-46122 (18 July 1966) --- Agena Target Docking Vehicle 5005 is photographed from the Gemini-Titan 10 (GT-10) spacecraft during rendezvous in space. The two spacecraft are about 38 feet apart. After docking with the Agena, astronauts John W. Young, command pilot, and Michael Collins, pilot, fired the 16,000 pound thrust engine of Agena X's primary propulsion system to boost the combined vehicles into an orbit with an apogee of 413 nautical miles to set a new altitude record for manned spaceflight. Photo credit: NASA

Conceptualization and design of a variable-gravity research facility

NASA Technical Reports Server (NTRS)

1987-01-01

The goal is to provide facilities for the study of the effects of variable-gravity levels in reducing the physiological stresses upon the humans of long-term stay time in zero-g. The designs studied include: twin-tethered two module system with a central despun module with docking port and winch gear; and rigid arm tube facility using shuttle external tanks. Topics examined included: despun central capsule configuration, docking clearances, EVA requirements, crew selection, crew scheduling, food supply and preparation, waste handling, leisure use, biomedical issues, and psycho-social issues.

Application of neural networks to autonomous rendezvous and docking of space vehicles

NASA Technical Reports Server (NTRS)

Dabney, Richard W.

1992-01-01

NASA-Marshall has investigated the feasibility of numerous autonomous rendezvous and docking (ARD) candidate techniques. Neural networks have been studied as a viable basis for such systems' implementation, due to their intrinsic representation of such nonlinear functions as those for which analytical solutions are either difficult or nonexistent. Neural networks are also able to recognize and adapt to changes in their dynamic environment, thereby enhancing redundancy and fault tolerance. Outstanding performance has been obtained from ARD azimuth, elevation, and roll networks of this type.

Space Tug Docking Study. Volume 5: Cost Analysis

NASA Technical Reports Server (NTRS)

1976-01-01

The cost methodology, summary cost data, resulting cost estimates by Work Breakdown Structure (WBS), technical characteristics data, program funding schedules and the WBS for the costing are discussed. Cost estimates for two tasks of the study are reported. The first, developed cost estimates for design, development, test and evaluation (DDT&E) and theoretical first unit (TFU) at the component level (Level 7) for all items reported in the data base. Task B developed total subsystem DDT&E costs and funding schedules for the three candidate Rendezvous and Docking Systems: manual, autonomous, and hybrid.

BUILDING A196 BARRACKS, FIRST FLOOR PLAN. Naval Guided Missile and ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

BUILDING A-196 BARRACKS, FIRST FLOOR PLAN. Naval Guided Missile and Tactical Data System School, Naval Schools Command, Mare Island, California. Milton T. Pflueger, Architect, 580 Market Street, San Francisco, CA. Sheet 126 of 145, specification 36050-61, approved for the Bureau of Yards and Docks, October 26, 1961. Yards and Docks drawing no. 892274; DPWO drawing no. B-75274; file no. 930-CR-1. 72 cm x 98 xm. Sepia tone print - Mare Island Naval Shipyard, Guard House & Barracks, Railroad Avenue near Eighteenth Street, Vallejo, Solano County, CA

BUILDING A196 BARRACKS, SECOND FLOOR PLAN. Naval Guided Missile and ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

BUILDING A-196 BARRACKS, SECOND FLOOR PLAN. Naval Guided Missile and Tactical Data System School, Naval Schools Command, Mare Island, CA. Milton T. Pflueger, Architect, 580 Market Street, San Francisco, CA. Sheet 127 to 145, specification 36050/61, approved for the Bureau of Yards and Docks, October 26, 1961. Yards and Docks drawing no. 892275; DPWO drawing no. B-75275; file no. 930-CR-2. 72 cm x 98 cm. Sepia tone print - Mare Island Naval Shipyard, Guard House & Barracks, Railroad Avenue near Eighteenth Street, Vallejo, Solano County, CA

Dual RF Astrodynamic GPS Orbital Navigator Satellite

NASA Technical Reports Server (NTRS)

Kanipe, David B.; Provence, Robert Steve; Straube, Timothy M.; Reed, Helen; Bishop, Robert; Lightsey, Glenn

2009-01-01

Dual RF Astrodynamic GPS Orbital Navigator Satellite (DRAGONSat) will demonstrate autonomous rendezvous and docking (ARD) in low Earth orbit (LEO) and gather flight data with a global positioning system (GPS) receiver strictly designed for space applications. ARD is the capability of two independent spacecraft to rendezvous in orbit and dock without crew intervention. DRAGONSat consists of two picosatellites (one built by the University of Texas and one built by Texas A and M University) and the Space Shuttle Payload Launcher (SSPL); this project will ultimately demonstrate ARD in LEO.

External view of Zarya and Zvezda taken during the STS-106 mission

NASA Image and Video Library

2000-09-11

S106-E-5116 (11 September 2000) --- This view of the International Space Station (ISS) was taken while it was docked with the Space Shuttle Atlantis and shows parts of all but one of the current components. From the top are the Progress supply vehicle, the Zvezda service module, and the Zarya functional cargo block (FGB). The Unity, now linked to the docking system of the Atlantis in the cargo bay, is out of view at bottom. A multicolored layer signals a sunset or sunrise on Earth at bottom left.

Saturn Apollo Program

NASA Image and Video Library

1973-01-01

This illustration depicts a configuration of the Soyuz spacecraft for the Apollo-Soyuz Test Project (ASTP). The ASTP was the first international docking of the U.S.'s Apollo spacecraft and the U.S.S.R.'s Soyuz spacecraft in space. For this project, the Soviets built another in their continuing series of Soyuz space capsules. The U.S. used the Saturn IB Apollo capsule. A joint engineering team from the two countries met to develop a docking system that permitted the two spacecraft to link in space and allowed the crews to travel from one spacecraft to the other.

Data Retrieved by ARCADE-R2 Experiment On Board the BEXUS-17 Balloon

NASA Astrophysics Data System (ADS)

Barbetta, M.; Branz, F.; Carron, A.; Olivieri, L.; Prendin, J.; Sansone, F.; Savioli, L.; Spinello, F.; Francesconi, A.

2015-09-01

The Autonomous Rendezvous, Control And Docking Experiment — Reflight 2 (ARCADE-R2) is a technology demonstrator aiming to prove automatic attitude determination and control, rendezvous and docking capabilities for small scale spacecraft and aircraft. The development of such capabilities could be fundamental to create, in the near future, fleets of cooperative, autonomous unmanned aerial vehicles for mapping, surveillance, inspection and remote observation of hazardous environments; small-class satellites could also benefit from the employment of docking systems to extend and reconfigure their mission profiles. ARCADE-R2 is designed to test these technologies on a stratospheric flight on board the BEXUS-17 balloon, allowing to demonstrate them in a harsh environment subjected to gusty winds and high pressure and temperature variations. In this paper, ARCADE-R2 architecture is introduced and the main results obtained from a stratospheric balloon flight are presented.

400mm Mapping Sequence performed during the STS-119 R-Bar Pitch Maneuver

NASA Image and Video Library

2008-03-17

ISS018-E-040791 (17 March 2009) --- Backdropped by a blanket of clouds, Space Shuttle Discovery is featured in this image photographed by an Expedition 18 crewmember on the International Space Station during rendezvous and docking operations. Before docking with the station, astronaut Lee Archambault, STS-119 commander, flew the shuttle through a Rendezvous Pitch Maneuver or basically a backflip to allow the space station crew a good view of Discovery's heat shield. Using digital still cameras equipped with both 400 and 800 millimeter lenses, the ISS crewmembers took a number of photos of the shuttle's thermal protection system and sent them down to teams on the ground for analysis. A 400 millimeter lens was used for this image. Docking occurred at 4:20 p.m. (CDT) on March 17, 2009. The final pair of power-generating solar array wings and the S6 truss segment are visible in Discovery?s cargo bay.

400mm Mapping Sequence performed during the STS-119 R-Bar Pitch Maneuver

NASA Image and Video Library

2008-03-17

ISS018-E-040792 (17 March 2009) --- Backdropped by a blanket of clouds, Space Shuttle Discovery is featured in this image photographed by an Expedition 18 crewmember on the International Space Station during rendezvous and docking operations. Before docking with the station, astronaut Lee Archambault, STS-119 commander, flew the shuttle through a Rendezvous Pitch Maneuver or basically a backflip to allow the space station crew a good view of Discovery's heat shield. Using digital still cameras equipped with both 400 and 800 millimeter lenses, the ISS crewmembers took a number of photos of the shuttle's thermal protection system and sent them down to teams on the ground for analysis. A 400 millimeter lens was used for this image. Docking occurred at 4:20 p.m. (CDT) on March 17, 2009. The final pair of power-generating solar array wings and the S6 truss segment are visible in Discovery?s cargo bay.

400mm Mapping Sequence performed during the STS-119 R-Bar Pitch Maneuver

NASA Image and Video Library

2008-03-17

ISS018-E-040790 (17 March 2009) --- Backdropped by the blackness of space, Space Shuttle Discovery is featured in this image photographed by an Expedition 18 crewmember on the International Space Station during rendezvous and docking operations. Before docking with the station, astronaut Lee Archambault, STS-119 commander, flew the shuttle through a Rendezvous Pitch Maneuver or basically a backflip to allow the space station crew a good view of Discovery's heat shield. Using digital still cameras equipped with both 400 and 800 millimeter lenses, the ISS crewmembers took a number of photos of the shuttle's thermal protection system and sent them down to teams on the ground for analysis. A 400 millimeter lens was used for this image. Docking occurred at 4:20 p.m. (CDT) on March 17, 2009. The final pair of power-generating solar array wings and the S6 truss segment are visible in Discovery?s cargo bay.

400mm Mapping Sequence performed during the STS-119 R-Bar Pitch Maneuver

NASA Image and Video Library

2008-03-17

ISS018-E-040789 (17 March 2009) --- Backdropped by the blackness of space, Space Shuttle Discovery is featured in this image photographed by an Expedition 18 crewmember on the International Space Station during rendezvous and docking operations. Before docking with the station, astronaut Lee Archambault, STS-119 commander, flew the shuttle through a Rendezvous Pitch Maneuver or basically a backflip to allow the space station crew a good view of Discovery's heat shield. Using digital still cameras equipped with both 400 and 800 millimeter lenses, the ISS crewmembers took a number of photos of the shuttle's thermal protection system and sent them down to teams on the ground for analysis. A 400 millimeter lens was used for this image. Docking occurred at 4:20 p.m. (CDT) on March 17, 2009. The final pair of power-generating solar array wings and the S6 truss segment are visible in Discovery’s cargo bay.

Space Shuttle Projects

NASA Image and Video Library

1995-06-01

This image of the Space Shuttle Orbiter Atlantis, with cargo bay doors open showing Spacelab Module for the Spacelab Life Science and the docking port, was photographed from the Russian Mir Space Station during STS-71 mission. The STS-71 mission performed the first docking with the Russian Mir Space Station to exchange crews. The Mir 19 crew, cosmonauts Anatoly Solovyev and Nikolai Budarin, replaced the Mir 18 crew, cosmonauts Valdamir Dezhurov and Gernady Strekalov, and astronaut Norman Thagard. Astronaut Thagard was launched aboard a Soyuz spacecraft in March 1995 for a three-month stay on the Mir Space Station as part of the Mir 18 crew. The Orbiter Atlantis was modified to carry a docking system compatible with the Mir Space Station. The Orbiter also carried a Spacelab module for the Spacelab Life Science mission in the payload bay in which various life science experiments and data collection took place throughout the 10-day mission.

Molecular Modeling, Docking, Dynamics and simulation of Gefitinib and its derivatives with EGFR in Non-Small Cell Lung Cancer.

PubMed

Reddy, Pulakuntla Swetha; Lokhande, Kiran Bharat; Nagar, Shuchi; Reddy, Vaddi Damodara; Murthy, P Sushma; Swamy, K Venkateswara

2018-02-27

Gefitinib (lressa) is the most prescribed drug, highly effective to treat of non-small cell lung cancer; primarily it was considered targeted therapy is a kinase inhibitor. The non-small cell lung cancer caused by the mutation in the Epithelial Growth Factor Receptor (EGFR) gene, Iressa works by blocking the EGFR protein that helps the cancer cell growth. EGFR protein has lead to the development of anticancer therapeutics directed against EGFR inhibitor including Gefitinib for non-small cell lung cancer. To explore research on Gefitinib and its derivatives interaction with crystal structure EGFR to understand the better molecular insights interaction strategies. Molecular modeling of ligands (Gefitinib and its derivatives) was carried out by Avogadro software till atomic angle stable confirmation obtained. The partial charges for the ligands were assigned as per standard protocol for molecular docking. All docking simulations were performed with AutoDockVina. Virtual screening carried out based on binding energy and hydrogen bonding affinity. Molecular dynamics (MD) and Simulation EGFR was done using GROMACS 5.1.1 software to explore the interaction stability in a cell. The stable conformation for EGFR protein trajectories were captured at various time intervals 0-20ns. Few compounds screen based on high affinity as the inhibitor for EGFR may inhibit the cell cycle signalling in non-small cell lung cancer. These result suggested that a computer aided screening approach of a Gefitinib derivatives compounds with regard to their binding to EGFR for identifying novel drugs for the treatment of non-small cell lung cancer. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

[Reference Intervals of Standard Test Items in Ningen Dock Examination].

PubMed

Yamakado, Minoru

2016-03-01

Reference intervals (RIs) were derived from records of 1,499,288 individuals who underwent ningen dock examination in 188 institutes which belong to Japan Society of Ningen Dock in 2012. Targets were 27 basic laboratory tests, including the body mass index (BMI) and systolic and diastolic blood pressures (SBP, DBP). Individuals fulfilling strict criteria were chosen: SBP < 130, DBP < 85 mmHg, BMI < 25 Kg/m2, non-smoking, ethanol consumption < 20 g/day, under no medication, with no remarkable current/past illness. The latent abnormal values exclusion (LAVE) method was applied to ensure normal results. RLs were derived using a parametric method with modified Box-Cox power transformation. Among all attendees, 23% fulfilled the criteria. Application of the LAVE method further reduced the dataset by 40-50%. RIs without distinction of the sex and age were SBP, DBP, TP, TB, MCV, WBC, and Plt. Sex-specific RIs were BMI, CRE, UA, TG, HDL-C, ALT, GGT, Glu, RBC, Hb, and Ht. Age-specific RIs in either sex were Alb, AST, HbA1c, TC, LDL-C, FW-LDL-C, nonHDL-C, and ALP. An age-specific RI without distinction of the sex was eGFR. Comparison of derived RIs with clinical decision limits (CDLs) revealed that the upper limits of RIs differed from CDLs according to the sex and age. Implementation of sex- and age-related RIs derived from individuals with fully normal ningen dock results will enable the appropriate interpretation of test results in health screening, and promote the effective application of CDLs for therapeutic intervention, taking into account the sex, age, and other health attributes.

In vitro, in silico and in vivo studies of ursolic acid as an anti-filarial agent.

PubMed

Kalani, Komal; Kushwaha, Vikas; Sharma, Pooja; Verma, Richa; Srivastava, Mukesh; Khan, Feroz; Murthy, P K; Srivastava, Santosh Kumar

2014-01-01

As part of our drug discovery program for anti-filarial agents from Indian medicinal plants, leaves of Eucalyptus tereticornis were chemically investigated, which resulted in the isolation and characterization of an anti-filarial agent, ursolic acid (UA) as a major constituent. Antifilarial activity of UA against the human lymphatic filarial parasite Brugia malayi using in vitro and in vivo assays, and in silico docking search on glutathione-s-transferase (GST) parasitic enzyme were carried out. The UA was lethal to microfilariae (mf; LC100: 50; IC50: 8.84 µM) and female adult worms (LC100: 100; IC50: 35.36 µM) as observed by motility assay; it exerted 86% inhibition in MTT reduction potential of the adult parasites. The selectivity index (SI) of UA for the parasites was found safe. This was supported by the molecular docking studies, which showed adequate docking (LibDock) scores for UA (-8.6) with respect to the standard antifilarial drugs, ivermectin (IVM -8.4) and diethylcarbamazine (DEC-C -4.6) on glutathione-s-transferase enzyme. Further, in silico pharmacokinetic and drug-likeness studies showed that UA possesses drug-like properties. Furthermore, UA was evaluated in vivo in B. malayi-M. coucha model (natural infection), which showed 54% macrofilaricidal activity, 56% female worm sterility and almost unchanged microfilaraemia maintained throughout observation period with no adverse effect on the host. Thus, in conclusion in vitro, in silico and in vivo results indicate that UA is a promising, inexpensive, widely available natural lead, which can be designed and developed into a macrofilaricidal drug. To the best of our knowledge this is the first ever report on the anti-filarial potential of UA from E. tereticornis, which is in full agreement with the Thomson Reuter's 'Metadrug' tool screening predictions.

APAS with petals extended after undocking

NASA Image and Video Library

2002-10-16

STS112-E-05777 (16 Oct. 2002) --- Close-up view of the Orbiter Docking System (ODS) Androgynous Peripheral Attachment System (APAS) petals extended in the STS-112 orbiter Atlantis payload bay after undocking with the International Space Station.

A manipulator arm for zero-g simulations

NASA Technical Reports Server (NTRS)

Brodie, S. B.; Grant, C.; Lazar, J. J.

1975-01-01

A 12-ft counterbalanced Slave Manipulator Arm (SMA) was designed and fabricated to be used for resolving the questions of operational applications, capabilities, and limitations for such remote manned systems as the Payload Deployment and Retrieval Mechanism (PDRM) for the shuttle, the Free-Flying Teleoperator System, the Advanced Space Tug, and Planetary Rovers. As a developmental tool for the shuttle manipulator system (or PDRM), the SMA represents an approximate one-quarter scale working model for simulating and demonstrating payload handling, docking assistance, and satellite servicing. For the Free-Flying Teleoperator System and the Advanced Tug, the SMA provides a near full-scale developmental tool for satellite servicing, docking, and deployment/retrieval procedures, techniques, and support equipment requirements. For the Planetary Rovers, it provides an oversize developmental tool for sample handling and soil mechanics investigations. The design of the SMA was based on concepts developed for a 40-ft NASA technology arm to be used for zero-g shuttle manipulator simulations.

An evaluation of coding methodologies for potential use in the Alabama Resource Information System (ARIS)-transportation study for the state of Alabama

NASA Technical Reports Server (NTRS)

Montgomery, O. L.

1977-01-01

Procedures developed for digitizing the transportation arteries, airports, and dock facilities of Alabama and placing them in a computerized format compatible with the Alabama Resource Information System are described. The time required to digitize by the following methods: (a) manual, (b) Telereadex 29 with film reading and digitizing system, and (c) digitizing tablets was evaluated. A method for digitizing and storing information from the U. T. M. grid cell base which was compatible with the system was developed and tested. The highways, navigable waterways, railroads, airports, and docks in the study area were digitized and the data stored. The manual method of digitizing was shown to be best for small amounts of data, while the graphic input from the digitizing tablets would be the best approach for entering the large amounts of data required for an entire state.

SAMICS marketing and distribution model

NASA Technical Reports Server (NTRS)

1978-01-01

A SAMICS (Solar Array Manufacturing Industry Costing Standards) was formulated as a computer simulation model. Given a proper description of the manufacturing technology as input, this model computes the manufacturing price of solar arrays for a broad range of production levels. This report presents a model for computing these marketing and distribution costs, the end point of the model being the loading dock of the final manufacturer.

Simulation of Mission Phases

NASA Technical Reports Server (NTRS)

Carlstrom, Nicholas Mercury

2016-01-01

This position with the Simulation and Graphics Branch (ER7) at Johnson Space Center (JSC) provided an introduction to vehicle hardware, mission planning, and simulation design. ER7 supports engineering analysis and flight crew training by providing high-fidelity, real-time graphical simulations in the Systems Engineering Simulator (SES) lab. The primary project assigned by NASA mentor and SES lab manager, Meghan Daley, was to develop a graphical simulation of the rendezvous, proximity operations, and docking (RPOD) phases of flight. The simulation is to include a generic crew/cargo transportation vehicle and a target object in low-Earth orbit (LEO). Various capsule, winged, and lifting body vehicles as well as historical RPOD methods were evaluated during the project analysis phase. JSC core mission to support the International Space Station (ISS), Commercial Crew Program (CCP), and Human Space Flight (HSF) influenced the project specifications. The simulation is characterized as a 30 meter +V Bar and/or -R Bar approach to the target object's docking station. The ISS was selected as the target object and the international Low Impact Docking System (iLIDS) was selected as the docking mechanism. The location of the target object's docking station corresponds with the RPOD methods identified. The simulation design focuses on Guidance, Navigation, and Control (GNC) system architecture models with station keeping and telemetry data processing capabilities. The optical and inertial sensors, reaction control system thrusters, and the docking mechanism selected were based on CCP vehicle manufacturer's current and proposed technologies. A significant amount of independent study and tutorial completion was required for this project. Multiple primary source materials were accessed using the NASA Technical Report Server (NTRS) and reference textbooks were borrowed from the JSC Main Library and International Space Station Library. The Trick Simulation Environment and User Training Materials version 2013.0 release was used to complete the Trick tutorial. Multiple network privilege and repository permission requests were required in order to access previous simulation models. The project was also an introduction to computer programming and the Linux operating system. Basic C++ and Python syntax was used during the completion of the Trick tutorial. Trick's engineering analysis and Monte Carlo simulation capabilities were observed and basic space mission planning procedures were applied in the conceptual design phase. Multiple professional development opportunities were completed in addition to project duties during this internship through the System for Administration, Training, and Education Resources for NASA (SATERN). Topics include: JSC Risk Management Workshop, CCP Risk Management, Basic Radiation Safety Training, X-Ray Radiation Safety, Basic Laser Safety, JSC Export Control, ISS RISE Ambassador, Basic SharePoint 2013, Space Nutrition and Biochemistry, and JSC Personal Protective Equipment. Additionally, this internship afforded the opportunity for formal project presentation and public speaking practice. This was my first experience at a NASA center. After completing this internship I have a much clearer understanding of certain aspects of the agency's processes and procedures, as well as a deeper appreciation from spaceflight simulation design and testing. I will continue to improve my technical skills so that I may have another opportunity to return to NASA and Johnson Space Center.

Structural Interface Parameters Are Discriminatory in Recognising Near-Native Poses of Protein-Protein Interactions

PubMed Central

Malhotra, Sony; Sankar, Kannan; Sowdhamini, Ramanathan

2014-01-01

Interactions at the molecular level in the cellular environment play a very crucial role in maintaining the physiological functioning of the cell. These molecular interactions exist at varied levels viz. protein-protein interactions, protein-nucleic acid interactions or protein-small molecules interactions. Presently in the field, these interactions and their mechanisms mark intensively studied areas. Molecular interactions can also be studied computationally using the approach named as Molecular Docking. Molecular docking employs search algorithms to predict the possible conformations for interacting partners and then calculates interaction energies. However, docking proposes number of solutions as different docked poses and hence offers a serious challenge to identify the native (or near native) structures from the pool of these docked poses. Here, we propose a rigorous scoring scheme called DockScore which can be used to rank the docked poses and identify the best docked pose out of many as proposed by docking algorithm employed. The scoring identifies the optimal interactions between the two protein partners utilising various features of the putative interface like area, short contacts, conservation, spatial clustering and the presence of positively charged and hydrophobic residues. DockScore was first trained on a set of 30 protein-protein complexes to determine the weights for different parameters. Subsequently, we tested the scoring scheme on 30 different protein-protein complexes and native or near-native structure were assigned the top rank from a pool of docked poses in 26 of the tested cases. We tested the ability of DockScore to discriminate likely dimer interactions that differ substantially within a homologous family and also demonstrate that DOCKSCORE can distinguish correct pose for all 10 recent CAPRI targets. PMID:24498255

Structural interface parameters are discriminatory in recognising near-native poses of protein-protein interactions.

PubMed

Malhotra, Sony; Sankar, Kannan; Sowdhamini, Ramanathan

2014-01-01

Interactions at the molecular level in the cellular environment play a very crucial role in maintaining the physiological functioning of the cell. These molecular interactions exist at varied levels viz. protein-protein interactions, protein-nucleic acid interactions or protein-small molecules interactions. Presently in the field, these interactions and their mechanisms mark intensively studied areas. Molecular interactions can also be studied computationally using the approach named as Molecular Docking. Molecular docking employs search algorithms to predict the possible conformations for interacting partners and then calculates interaction energies. However, docking proposes number of solutions as different docked poses and hence offers a serious challenge to identify the native (or near native) structures from the pool of these docked poses. Here, we propose a rigorous scoring scheme called DockScore which can be used to rank the docked poses and identify the best docked pose out of many as proposed by docking algorithm employed. The scoring identifies the optimal interactions between the two protein partners utilising various features of the putative interface like area, short contacts, conservation, spatial clustering and the presence of positively charged and hydrophobic residues. DockScore was first trained on a set of 30 protein-protein complexes to determine the weights for different parameters. Subsequently, we tested the scoring scheme on 30 different protein-protein complexes and native or near-native structure were assigned the top rank from a pool of docked poses in 26 of the tested cases. We tested the ability of DockScore to discriminate likely dimer interactions that differ substantially within a homologous family and also demonstrate that DOCKSCORE can distinguish correct pose for all 10 recent CAPRI targets.

Lessons in molecular recognition: the effects of ligand and protein flexibility on molecular docking accuracy.

PubMed

Erickson, Jon A; Jalaie, Mehran; Robertson, Daniel H; Lewis, Richard A; Vieth, Michal

2004-01-01

The key to success for computational tools used in structure-based drug design is the ability to accurately place or "dock" a ligand in the binding pocket of the target of interest. In this report we examine the effect of several factors on docking accuracy, including ligand and protein flexibility. To examine ligand flexibility in an unbiased fashion, a test set of 41 ligand-protein cocomplex X-ray structures were assembled that represent a diversity of size, flexibility, and polarity with respect to the ligands. Four docking algorithms, DOCK, FlexX, GOLD, and CDOCKER, were applied to the test set, and the results were examined in terms of the ability to reproduce X-ray ligand positions within 2.0A heavy atom root-mean-square deviation. Overall, each method performed well (>50% accuracy) but for all methods it was found that docking accuracy decreased substantially for ligands with eight or more rotatable bonds. Only CDOCKER was able to accurately dock most of those ligands with eight or more rotatable bonds (71% accuracy rate). A second test set of structures was gathered to examine how protein flexibility influences docking accuracy. CDOCKER was applied to X-ray structures of trypsin, thrombin, and HIV-1-protease, using protein structures bound to several ligands and also the unbound (apo) form. Docking experiments of each ligand to one "average" structure and to the apo form were carried out, and the results were compared to docking each ligand back to its originating structure. The results show that docking accuracy falls off dramatically if one uses an average or apo structure. In fact, it is shown that the drop in docking accuracy mirrors the degree to which the protein moves upon ligand binding.

Human and server docking prediction for CAPRI round 30-35 using LZerD with combined scoring functions.

PubMed

Peterson, Lenna X; Kim, Hyungrae; Esquivel-Rodriguez, Juan; Roy, Amitava; Han, Xusi; Shin, Woong-Hee; Zhang, Jian; Terashi, Genki; Lee, Matt; Kihara, Daisuke

2017-03-01

We report the performance of protein-protein docking predictions by our group for recent rounds of the Critical Assessment of Prediction of Interactions (CAPRI), a community-wide assessment of state-of-the-art docking methods. Our prediction procedure uses a protein-protein docking program named LZerD developed in our group. LZerD represents a protein surface with 3D Zernike descriptors (3DZD), which are based on a mathematical series expansion of a 3D function. The appropriate soft representation of protein surface with 3DZD makes the method more tolerant to conformational change of proteins upon docking, which adds an advantage for unbound docking. Docking was guided by interface residue prediction performed with BindML and cons-PPISP as well as literature information when available. The generated docking models were ranked by a combination of scoring functions, including PRESCO, which evaluates the native-likeness of residues' spatial environments in structure models. First, we discuss the overall performance of our group in the CAPRI prediction rounds and investigate the reasons for unsuccessful cases. Then, we examine the performance of several knowledge-based scoring functions and their combinations for ranking docking models. It was found that the quality of a pool of docking models generated by LZerD, that is whether or not the pool includes near-native models, can be predicted by the correlation of multiple scores. Although the current analysis used docking models generated by LZerD, findings on scoring functions are expected to be universally applicable to other docking methods. Proteins 2017; 85:513-527. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Validation studies of the site-directed docking program LibDock.

PubMed

Rao, Shashidhar N; Head, Martha S; Kulkarni, Amit; LaLonde, Judith M

2007-01-01

The performance of the site-features docking algorithm LibDock has been evaluated across eight GlaxoSmithKline targets as a follow-up to a broad validation study of docking and scoring software (Warren, G. L.; Andrews, W. C.; Capelli, A.; Clarke, B.; Lalonde, J.; Lambert, M. H.; Lindvall, M.; Nevins, N.; Semus, S. F.; Senger, S.; Tedesco, G.; Walls, I. D.; Woolven, J. M.; Peishoff, C. E.; Head, M. S. J. Med. Chem. 2006, 49, 5912-5931). Docking experiments were performed to assess both the accuracy in reproducing the binding mode of the ligand and the retrieval of active compounds in a virtual screening protocol using both the DJD (Diller, D. J.; Merz, K. M., Jr. Proteins 2001, 43, 113-124) and LigScore2 (Krammer, A. K.; Kirchoff, P. D.; Jiang, X.; Venkatachalam, C. M.; Waldman, M. J. Mol. Graphics Modell. 2005, 23, 395-407) scoring functions. This study was conducted using DJD scoring, and poses were rescored using all available scoring functions in the Accelrys LigandFit module, including LigScore2. For six out of eight targets at least 30% of the ligands were docked within a root-mean-square difference (RMSD) of 2.0 A for the crystallographic poses when the LigScore2 scoring function was used. LibDock retrieved at least 20% of active compounds in the top 10% of screened ligands for four of the eight targets in the virtual screening protocol. In both studies the LigScore2 scoring function enhanced the retrieval of crystallographic poses or active compounds in comparison with the results obtained using the DJD scoring function. The results for LibDock accuracy and ligand retrieval in virtual screening are compared to 10 other docking and scoring programs. These studies demonstrate the utility of the LigScore2 scoring function and that LibDock as a feature directed docking method performs as well as docking programs that use genetic/growing and Monte Carlo driven algorithms.

Protein-protein docking using region-based 3D Zernike descriptors

PubMed Central

2009-01-01

Background Protein-protein interactions are a pivotal component of many biological processes and mediate a variety of functions. Knowing the tertiary structure of a protein complex is therefore essential for understanding the interaction mechanism. However, experimental techniques to solve the structure of the complex are often found to be difficult. To this end, computational protein-protein docking approaches can provide a useful alternative to address this issue. Prediction of docking conformations relies on methods that effectively capture shape features of the participating proteins while giving due consideration to conformational changes that may occur. Results We present a novel protein docking algorithm based on the use of 3D Zernike descriptors as regional features of molecular shape. The key motivation of using these descriptors is their invariance to transformation, in addition to a compact representation of local surface shape characteristics. Docking decoys are generated using geometric hashing, which are then ranked by a scoring function that incorporates a buried surface area and a novel geometric complementarity term based on normals associated with the 3D Zernike shape description. Our docking algorithm was tested on both bound and unbound cases in the ZDOCK benchmark 2.0 dataset. In 74% of the bound docking predictions, our method was able to find a near-native solution (interface C-αRMSD ≤ 2.5 Å) within the top 1000 ranks. For unbound docking, among the 60 complexes for which our algorithm returned at least one hit, 60% of the cases were ranked within the top 2000. Comparison with existing shape-based docking algorithms shows that our method has a better performance than the others in unbound docking while remaining competitive for bound docking cases. Conclusion We show for the first time that the 3D Zernike descriptors are adept in capturing shape complementarity at the protein-protein interface and useful for protein docking prediction. Rigorous benchmark studies show that our docking approach has a superior performance compared to existing methods. PMID:20003235

Protein-protein docking using region-based 3D Zernike descriptors.

PubMed

Venkatraman, Vishwesh; Yang, Yifeng D; Sael, Lee; Kihara, Daisuke

2009-12-09

Protein-protein interactions are a pivotal component of many biological processes and mediate a variety of functions. Knowing the tertiary structure of a protein complex is therefore essential for understanding the interaction mechanism. However, experimental techniques to solve the structure of the complex are often found to be difficult. To this end, computational protein-protein docking approaches can provide a useful alternative to address this issue. Prediction of docking conformations relies on methods that effectively capture shape features of the participating proteins while giving due consideration to conformational changes that may occur. We present a novel protein docking algorithm based on the use of 3D Zernike descriptors as regional features of molecular shape. The key motivation of using these descriptors is their invariance to transformation, in addition to a compact representation of local surface shape characteristics. Docking decoys are generated using geometric hashing, which are then ranked by a scoring function that incorporates a buried surface area and a novel geometric complementarity term based on normals associated with the 3D Zernike shape description. Our docking algorithm was tested on both bound and unbound cases in the ZDOCK benchmark 2.0 dataset. In 74% of the bound docking predictions, our method was able to find a near-native solution (interface C-alphaRMSD < or = 2.5 A) within the top 1000 ranks. For unbound docking, among the 60 complexes for which our algorithm returned at least one hit, 60% of the cases were ranked within the top 2000. Comparison with existing shape-based docking algorithms shows that our method has a better performance than the others in unbound docking while remaining competitive for bound docking cases. We show for the first time that the 3D Zernike descriptors are adept in capturing shape complementarity at the protein-protein interface and useful for protein docking prediction. Rigorous benchmark studies show that our docking approach has a superior performance compared to existing methods.

6. Looking west showing top of dock: steaming frozen ore ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

6. Looking west showing top of dock: steaming frozen ore which had been put in pockets in December 1959, May 6, 1990. Photographer: unknown - Marquette Ore Dock No. 6, Ore Dock, On pilings in Marquette City Lower Harbor, Marquette, Marquette County, MI

Fast and accurate grid representations for atom-based docking with partner flexibility.

PubMed

de Vries, Sjoerd J; Zacharias, Martin

2017-06-30

Macromolecular docking methods can broadly be divided into geometric and atom-based methods. Geometric methods use fast algorithms that operate on simplified, grid-like molecular representations, while atom-based methods are more realistic and flexible, but far less efficient. Here, a hybrid approach of grid-based and atom-based docking is presented, combining precalculated grid potentials with neighbor lists for fast and accurate calculation of atom-based intermolecular energies and forces. The grid representation is compatible with simultaneous multibody docking and can tolerate considerable protein flexibility. When implemented in our docking method ATTRACT, grid-based docking was found to be ∼35x faster. With the OPLSX forcefield instead of the ATTRACT coarse-grained forcefield, the average speed improvement was >100x. Grid-based representations may allow atom-based docking methods to explore large conformational spaces with many degrees of freedom, such as multiple macromolecules including flexibility. This increases the domain of biological problems to which docking methods can be applied. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Independent signaling by Drosophila insulin receptor for axon guidance and growth

PubMed Central

Li, Caroline R.; Guo, Dongyu; Pick, Leslie

2014-01-01

The Drosophila insulin receptor (DInR) regulates a diverse array of biological processes including growth, axon guidance, and sugar homeostasis. Growth regulation by DInR is mediated by Chico, the Drosophila homolog of vertebrate insulin receptor substrate proteins IRS1–4. In contrast, DInR regulation of photoreceptor axon guidance in the developing visual system is mediated by the SH2-SH3 domain adaptor protein Dreadlocks (Dock). In vitro studies by others identified five NPXY motifs, one in the juxtamembrane region and four in the signaling C-terminal tail (C-tail), important for interaction with Chico. Here we used yeast two-hybrid assays to identify regions in the DInR C-tail that interact with Dock. These Dock binding sites were in separate portions of the C-tail from the previously identified Chico binding sites. To test whether these sites are required for growth or axon guidance in whole animals, a panel of DInR proteins, in which the putative Chico and Dock interaction sites had been mutated individually or in combination, were tested for their ability to rescue viability, growth and axon guidance defects of dinr mutant flies. Sites required for viability were identified. Unexpectedly, mutation of both putative Dock binding sites, either individually or in combination, did not lead to defects in photoreceptor axon guidance. Thus, either sites also required for viability are necessary for DInR function in axon guidance and/or there is redundancy built into the DInR/Dock interaction such that Dock is able to interact with multiple regions of DInR. We also found that simultaneous mutation of all five NPXY motifs implicated in Chico interaction drastically decreased growth in both male and female adult flies. These animals resembled chico mutants, supporting the notion that DInR interacts directly with Chico in vivo to control body size. Mutation of these five NPXY motifs did not affect photoreceptor axon guidance, segregating the roles of DInR in the processes of growth and axon guidance. PMID:24478707

Surflex-Dock: Docking benchmarks and real-world application

NASA Astrophysics Data System (ADS)

Spitzer, Russell; Jain, Ajay N.

2012-06-01

Benchmarks for molecular docking have historically focused on re-docking the cognate ligand of a well-determined protein-ligand complex to measure geometric pose prediction accuracy, and measurement of virtual screening performance has been focused on increasingly large and diverse sets of target protein structures, cognate ligands, and various types of decoy sets. Here, pose prediction is reported on the Astex Diverse set of 85 protein ligand complexes, and virtual screening performance is reported on the DUD set of 40 protein targets. In both cases, prepared structures of targets and ligands were provided by symposium organizers. The re-prepared data sets yielded results not significantly different than previous reports of Surflex-Dock on the two benchmarks. Minor changes to protein coordinates resulting from complex pre-optimization had large effects on observed performance, highlighting the limitations of cognate ligand re-docking for pose prediction assessment. Docking protocols developed for cross-docking, which address protein flexibility and produce discrete families of predicted poses, produced substantially better performance for pose prediction. Performance on virtual screening performance was shown to benefit by employing and combining multiple screening methods: docking, 2D molecular similarity, and 3D molecular similarity. In addition, use of multiple protein conformations significantly improved screening enrichment.

Extracellular domains play different roles in gap junction formation and docking compatibility.

PubMed

Bai, Donglin; Wang, Ao Hong

2014-02-15

GJ (gap junction) channels mediate direct intercellular communication and play an important role in many physiological processes. Six connexins oligomerize to form a hemichannel and two hemichannels dock together end-to-end to form a GJ channel. Connexin extracellular domains (E1 and E2) have been shown to be important for the docking, but the molecular mechanisms behind the docking and formation of GJ channels are not clear. Recent developments in atomic GJ structure and functional studies on a series of connexin mutants revealed that E1 and E2 are likely to play different roles in the docking. Non-covalent interactions at the docking interface, including hydrogen bonds, are predicted to form between interdocked extracellular domains. Protein sequence alignment analysis on the docking compatible/incompatible connexins indicate that the E1 domain is important for the formation of the GJ channel and the E2 domain is important in the docking compatibility in heterotypic channels. Interestingly, the hydrogen-bond forming or equivalent residues in both E1 and E2 domains are mutational hot spots for connexin-linked human diseases. Understanding the molecular mechanisms of GJ docking can assist us to develop novel strategies in rescuing the disease-linked connexin mutants.

In Silico Screening for Biothreat Countermeasures

DTIC Science & Technology

2006-02-03

drug candidates to each kinase structure using the well-known docking algorithm LibDock . This population of 1200 ligands includes ~400 ligands with...mentioned previously, each of the known p38 inhibitors in the population was docked to its target using the LibDock application. This method resulted

Exploring the novel heterocyclic derivatives as lead molecules for design and development of potent anticancer agents.

PubMed

Azad, Iqbal; Nasibullah, Malik; Khan, Tahmeena; Hassan, Firoj; Akhter, Yusuf

2018-05-01

This paper deals with in silico evaluation of newly proposed heterocyclic derivatives in search of potential anticancer activity. Best possible drug candidates have been proposed using a rational approach employing a pipeline of computational techniques namely MetaPrint2D prediction, molinspiration, cheminformatics, Osiris Data warrior, AutoDock and iGEMDOCK. Lazar toxicity prediction, AdmetSAR predictions, and targeted docking studies were also performed. 27 heterocyclic derivatives were selected for bioactivity prediction and drug likeness score on the basis of Lipinski's rule, Viber rule, Ghose filter, leadlikeness and Pan Assay Interference Compounds (PAINS) rule. Bufuralol, Sunitinib, and Doxorubicin were selected as reference standard drug for the comparison of molecular descriptors and docking. Bufuralol is a known non-selective adreno-receptor blocking agent. Studies showed that beta blockers are also used against different types of cancers. Sunitinib is well known Food and Drug administration (FDA) approved pyrrole containing tyrosine kinase inhibitor and our proposed molecules possess similarities with both drug and doxorubicin is another moiety having anticancer activity. All heterocyclic derivatives were found to obey the drug filters except standard drug Doxorubicin. Bioactivity score of the compounds was predicted for drug targets including enzymes, nuclear receptors, kinase inhibitors, G protein-coupled receptor (GPCR) ligands and ion channel modulators. Absorption, distribution, metabolism and toxicity (ADMET) prediction of all proposed compound showed good Blood-brain barrier (BBB) penetration, Human intestinal absorption (HIA), Caco-2 cell permeability except compound-11 and was found to have no AdmetSAR toxicity as well as carcinogenic effect. Compounds 1-9 were slightly mutagenic while compound 2, 11, 20 and 21 showed carcinogenic effect according to Lazar toxicity prediction. Rests of the compounds were predicted to have no side effect. Molecular docking was performed with vascular endothelial growth factor receptor-2(VEGFR2) and glutathione S-transferase-1 (GSTP1) because both are common cancer causing proteins. Sunitinib and Doxorubicin possess great affinity to inhibit these cancers causing protein. Self-organizing map (SOM) was used to depict data in a simple 2D presentation. Our studies justify that good oral bioavailability and therapeutic efficacy of 10, 12-19 and 22-27 compounds can be considered as potential anticancer agents. Copyright © 2018 Elsevier Inc. All rights reserved.

Six degree of freedom simulation system for evaluating automated rendezvous and docking spacecraft

NASA Technical Reports Server (NTRS)

Rourke, Kenneth H.; Tsugawa, Roy K.

1991-01-01

Future logistics supply and servicing vehicles such as cargo transfer vehicles (CTV) must have full 6 degree of freedom (6DOF) capability in order to perform requisite rendezvous, proximity operations, and capture operations. The design and performance issues encountered when developing a 6DOF maneuvering spacecraft are very complex with subtle interactions which are not immediately obvious or easily anticipated. In order to deal with these complexities and develop robust maneuvering spacecraft designs, a simulation system and associated family of tools are used at TRW for generating and validating spacecraft performance requirements and guidance algorithms. An overview of the simulator and tools is provided. These are used by TRW for autonomous rendezvous and docking research projects including CTV studies.

HDOCK: a web server for protein–protein and protein–DNA/RNA docking based on a hybrid strategy

PubMed Central

Yan, Yumeng; Zhang, Di; Zhou, Pei; Li, Botong

2017-01-01

Abstract Protein–protein and protein–DNA/RNA interactions play a fundamental role in a variety of biological processes. Determining the complex structures of these interactions is valuable, in which molecular docking has played an important role. To automatically make use of the binding information from the PDB in docking, here we have presented HDOCK, a novel web server of our hybrid docking algorithm of template-based modeling and free docking, in which cases with misleading templates can be rescued by the free docking protocol. The server supports protein–protein and protein–DNA/RNA docking and accepts both sequence and structure inputs for proteins. The docking process is fast and consumes about 10–20 min for a docking run. Tested on the cases with weakly homologous complexes of <30% sequence identity from five docking benchmarks, the HDOCK pipeline tied with template-based modeling on the protein–protein and protein–DNA benchmarks and performed better than template-based modeling on the three protein–RNA benchmarks when the top 10 predictions were considered. The performance of HDOCK became better when more predictions were considered. Combining the results of HDOCK and template-based modeling by ranking first of the template-based model further improved the predictive power of the server. The HDOCK web server is available at http://hdock.phys.hust.edu.cn/. PMID:28521030

Calculating an optimal box size for ligand docking and virtual screening against experimental and predicted binding pockets.

PubMed

Feinstein, Wei P; Brylinski, Michal

2015-01-01

Computational approaches have emerged as an instrumental methodology in modern research. For example, virtual screening by molecular docking is routinely used in computer-aided drug discovery. One of the critical parameters for ligand docking is the size of a search space used to identify low-energy binding poses of drug candidates. Currently available docking packages often come with a default protocol for calculating the box size, however, many of these procedures have not been systematically evaluated. In this study, we investigate how the docking accuracy of AutoDock Vina is affected by the selection of a search space. We propose a new procedure for calculating the optimal docking box size that maximizes the accuracy of binding pose prediction against a non-redundant and representative dataset of 3,659 protein-ligand complexes selected from the Protein Data Bank. Subsequently, we use the Directory of Useful Decoys, Enhanced to demonstrate that the optimized docking box size also yields an improved ranking in virtual screening. Binding pockets in both datasets are derived from the experimental complex structures and, additionally, predicted by eFindSite. A systematic analysis of ligand binding poses generated by AutoDock Vina shows that the highest accuracy is achieved when the dimensions of the search space are 2.9 times larger than the radius of gyration of a docking compound. Subsequent virtual screening benchmarks demonstrate that this optimized docking box size also improves compound ranking. For instance, using predicted ligand binding sites, the average enrichment factor calculated for the top 1 % (10 %) of the screening library is 8.20 (3.28) for the optimized protocol, compared to 7.67 (3.19) for the default procedure. Depending on the evaluation metric, the optimal docking box size gives better ranking in virtual screening for about two-thirds of target proteins. This fully automated procedure can be used to optimize docking protocols in order to improve the ranking accuracy in production virtual screening simulations. Importantly, the optimized search space systematically yields better results than the default method not only for experimental pockets, but also for those predicted from protein structures. A script for calculating the optimal docking box size is freely available at www.brylinski.org/content/docking-box-size. Graphical AbstractWe developed a procedure to optimize the box size in molecular docking calculations. Left panel shows the predicted binding pose of NADP (green sticks) compared to the experimental complex structure of human aldose reductase (blue sticks) using a default protocol. Right panel shows the docking accuracy using an optimized box size.

Early clinical experience with the da Vinci Xi Surgical System in general surgery.

PubMed

Hagen, Monika E; Jung, Minoa K; Ris, Frederic; Fakhro, Jassim; Buchs, Nicolas C; Buehler, Leo; Morel, Philippe

2017-09-01

The da Vinci Xi Surgical System (Intuitive Surgical Inc., Sunnyvale, CA, USA) has been released in 2014 to facilitate minimally invasive surgery. Novel features are targeted towards facilitating complex multi-quadrant procedures, but data is scarce so far. Perioperative data of patients who underwent robotic general surgery with the da Vinci Xi system within the first 6 month after installation were collected and analyzed. The gastric bypass procedures performed with the da Vinci Xi Surgical System were compared to an equal amount of the last procedures with the da Vinci Si Surgical System. Thirty-one foregut (28 Roux-en-Y gastric bypasses), 6 colorectal procedures and 1 revisional biliary procedure were performed. The mean operating room (OR) time was 221.8 (±69.0) minutes for gastric bypasses and 306.5 (±48.8) for colorectal procedures with mean docking time of 9.4 (±3.8) minutes. The gastric bypass procedure was transitioned from a hybrid to a fully robotic approach. In comparison to the last 28 gastric bypass procedures performed with the da Vinci Si Surgical System, the OR time was comparable (226.9 versus 230.6 min, p = 0.8094), but the docking time significantly longer with the da Vinci Xi Surgical System (8.5 versus 6.1 min, p = 0.0415). All colorectal procedures were performed with a single robotic docking. No intraoperative and two postoperative complications occurred. The da Vinci Xi might facilitate single-setups of totally robotic gastric bypass and colorectal surgeries. However, further comparable research is needed to clearly determine the significance of this latest version of the da Vinci Surgical System.

Stimulation of insulin release by glucose is associated with an increase in the number of docked granules in the beta-cells of rat pancreatic islets.

PubMed

Straub, Susanne G; Shanmugam, Geetha; Sharp, Geoffrey W G

2004-12-01

Electron microscopy and quantitative stereological techniques were used to study the dynamics of the docked granule pool in the rat pancreatic beta-cell. The mean number of granules per beta-cell was 11,136. After equilibration in RPMI containing 5.6 mmol/l glucose, 6.4% of the granules (approximately 700) were docked at the plasma membrane (also measured as [means +/- SE] 4.3 +/- 0.6 docked granules per 10 microm of plasma membrane at the perimeter of the cell sections). After a 40-min exposure to 16.7 mmol/l glucose, 10.2% of the granules (approximately 1,060) were docked (6.4 +/- 0.8 granules per 10 microm of plasma membrane). Thus, the docked pool increased by 50% during stimulation with glucose. Islets were also exposed to 16.7 mmol/l glucose in the absence or presence of 10 micromol/l nitrendipine. In the absence and presence of nitrendipine, there were 6.1 +/- 0.7 and 6.3 +/- 0.6 granules per 10 microm of membrane, respectively. Thus, glucose increased granule docking independently of increased [Ca2+]i and exocytosis. The data suggest a limit to the number of docking sites. As the rate of docking exceeded the rate of exocytosis, docking is not rate limiting for insulin release. Only with extremely high release rates, glucose stimulation after a 4-h incubation with a high concentration of fatty acid-free BSA, was the docked granule pool reduced in size.

Imaging Flash Lidar for Autonomous Safe Landing and Spacecraft Proximity Operation

NASA Technical Reports Server (NTRS)

Amzajerdian, Farzin; Roback, Vincent E.; Brewster, Paul F.; Hines, Glenn D.; Bulyshev, Alexander E.

2016-01-01

3-D Imaging flash lidar is recognized as a primary candidate sensor for safe precision landing on solar system bodies (Moon, Mars, Jupiter and Saturn moons, etc.), and autonomous rendezvous proximity operations and docking/capture necessary for asteroid sample return and redirect missions, spacecraft docking, satellite servicing, and space debris removal. During the final stages of landing, from about 1 km to 500 m above the ground, the flash lidar can generate 3-Dimensional images of the terrain to identify hazardous features such as craters, rocks, and steep slopes. The onboard fli1ght computer can then use the 3-D map of terrain to guide the vehicle to a safe location. As an automated rendezvous and docking sensor, the flash lidar can provide relative range, velocity, and bearing from an approaching spacecraft to another spacecraft or a space station from several kilometers distance. NASA Langley Research Center has developed and demonstrated a flash lidar sensor system capable of generating 16k pixels range images with 7 cm precision, at a 20 Hz frame rate, from a maximum slant range of 1800 m from the target area. This paper describes the lidar instrument design and capabilities as demonstrated by the closed-loop flight tests onboard a rocket-propelled free-flyer vehicle (Morpheus). Then a plan for continued advancement of the flash lidar technology will be explained. This proposed plan is aimed at the development of a common sensor that with a modest design adjustment can meet the needs of both landing and proximity operation and docking applications.

Geostationary platform systems concepts definition study. Volume 2: Technical, book 2

NASA Technical Reports Server (NTRS)

1980-01-01

A selected concept for a geostationary platform is defined in sufficient detail to identify requirements for supporting research and technology, space demonstrations, GFE interfaces, costs, and schedules. This system consists of six platforms in geostationary orbit (GEO) over the Western Hemisphere and six over the Atlantic, to satisfy the total payload set associated with the nominal traffic model. Each platform is delivered to low Earth orbit (LEO) in a single shuttle flight, already mated to its LEO to GEO transfer vehicle and ready for deployment and transfer to GEO. An alternative concept is looked at briefly for comparison of configuration and technology requirements. This alternative consists of two large platforms, one over the Western Hemisphere consisting of three docked modules, and one over the Atlantic (two docked modules), to satisfy a high traffic model. The modules are full length orbiter cargo bay payloads, mated at LEO to orbital transfer vehicles (OTVs) delivered in other shuttle flights, for transfer to GEO, rendezvous, and docking. A preliminary feasibility study of an experimental platform is also performed to demonstrate communications and platform technologies required for the operational platforms of the 1990s.

Voss with docking probe in Service module

NASA Image and Video Library

2001-05-30

ISS002-E-6478 (30 May 2001) --- James S. Voss, Expedition Two flight engineer, handles a spacecraft docking probe in the Service Module. The docking probe assists with the docking of the Soyuz and Progress vehicles to the International Space Station. The image was taken with a digital still camera.