Introducing Molecular Life Science Students to Model Building Using Computer Simulations

ERIC Educational Resources Information Center

Aegerter-Wilmsen, Tinri; Kettenis, Dik; Sessink, Olivier; Hartog, Rob; Bisseling, Ton; Janssen, Fred

2006-01-01

Computer simulations can facilitate the building of models of natural phenomena in research, such as in the molecular life sciences. In order to introduce molecular life science students to the use of computer simulations for model building, a digital case was developed in which students build a model of a pattern formation process in…

Magnetohydrodynamic Models of Molecular Tornadoes

NASA Astrophysics Data System (ADS)

Au, Kelvin; Fiege, Jason D.

2017-07-01

Recent observations near the Galactic Center (GC) have found several molecular filaments displaying striking helically wound morphology that are collectively known as molecular tornadoes. We investigate the equilibrium structure of these molecular tornadoes by formulating a magnetohydrodynamic model of a rotating, helically magnetized filament. A special analytical solution is derived where centrifugal forces balance exactly with toroidal magnetic stress. From the physics of torsional Alfvén waves we derive a constraint that links the toroidal flux-to-mass ratio and the pitch angle of the helical field to the rotation laws, which we find to be an important component in describing the molecular tornado structure. The models are compared to the Ostriker solution for isothermal, nonmagnetic, nonrotating filaments. We find that neither the analytic model nor the Alfvén wave model suffer from the unphysical density inversions noted by other authors. A Monte Carlo exploration of our parameter space is constrained by observational measurements of the Pigtail Molecular Cloud, the Double Helix Nebula, and the GC Molecular Tornado. Observable properties such as the velocity dispersion, filament radius, linear mass, and surface pressure can be used to derive three dimensionless constraints for our dimensionless models of these three objects. A virial analysis of these constrained models is studied for these three molecular tornadoes. We find that self-gravity is relatively unimportant, whereas magnetic fields and external pressure play a dominant role in the confinement and equilibrium radial structure of these objects.

To What Degree Does Handling Concrete Molecular Models Promote the Ability to Translate and Coordinate between 2D and 3D Molecular Structure Representations? A Case Study with Algerian Students

ERIC Educational Resources Information Center

Mohamed-Salah, Boukhechem; Alain, Dumon

2016-01-01

This study aims to assess whether the handling of concrete ball-and-stick molecular models promotes translation between diagrammatic representations and a concrete model (or vice versa) and the coordination of the different types of structural representations of a given molecular structure. Forty-one Algerian undergraduate students were requested…

Modeling the chemistry of complex petroleum mixtures.

PubMed Central

Quann, R J

1998-01-01

Determining the complete molecular composition of petroleum and its refined products is not feasible with current analytical techniques because of the astronomical number of molecular components. Modeling the composition and behavior of such complex mixtures in refinery processes has accordingly evolved along a simplifying concept called lumping. Lumping reduces the complexity of the problem to a manageable form by grouping the entire set of molecular components into a handful of lumps. This traditional approach does not have a molecular basis and therefore excludes important aspects of process chemistry and molecular property fundamentals from the model's formulation. A new approach called structure-oriented lumping has been developed to model the composition and chemistry of complex mixtures at a molecular level. The central concept is to represent an individual molecular or a set of closely related isomers as a mathematical construct of certain specific and repeating structural groups. A complex mixture such as petroleum can then be represented as thousands of distinct molecular components, each having a mathematical identity. This enables the automated construction of large complex reaction networks with tens of thousands of specific reactions for simulating the chemistry of complex mixtures. Further, the method provides a convenient framework for incorporating molecular physical property correlations, existing group contribution methods, molecular thermodynamic properties, and the structure--activity relationships of chemical kinetics in the development of models. PMID:9860903

3D-QSAR (CoMFA, CoMSIA), molecular docking and molecular dynamics simulations study of 6-aryl-5-cyano-pyrimidine derivatives to explore the structure requirements of LSD1 inhibitors.

PubMed

Ding, Lina; Wang, Zhi-Zheng; Sun, Xu-Dong; Yang, Jing; Ma, Chao-Ya; Li, Wen; Liu, Hong-Min

2017-08-01

Recently, Histone Lysine Specific Demethylase 1 (LSD1) was regarded as a promising anticancer target for the novel drug discovery. And several small molecules as LSD1 inhibitors in different structures have been reported. In this work, we carried out a molecular modeling study on the 6-aryl-5-cyano-pyrimidine fragment LSD1 inhibitors using three-dimensional quantitative structure-activity relationship (3D-QSAR), molecular docking and molecular dynamics simulations. Comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were used to generate 3D-QSAR models. The results show that the best CoMFA model has q 2 =0.802, r 2 ncv =0.979, and the best CoMSIA model has q 2 =0.799, r 2 ncv =0.982. The electrostatic, hydrophobic and H-bond donor fields play important roles in the models. Molecular docking studies predict the binding mode and the interactions between the ligand and the receptor protein. Molecular dynamics simulations results reveal that the complex of the ligand and the receptor protein are stable at 300K. All the results can provide us more useful information for our further drug design. Copyright © 2017. Published by Elsevier Ltd.

Computer-Based Molecular Modelling: Finnish School Teachers' Experiences and Views

ERIC Educational Resources Information Center

Aksela, Maija; Lundell, Jan

2008-01-01

Modern computer-based molecular modelling opens up new possibilities for chemistry teaching at different levels. This article presents a case study seeking insight into Finnish school teachers' use of computer-based molecular modelling in teaching chemistry, into the different working and teaching methods used, and their opinions about necessary…

Implementing a modeling software for animated protein-complex interactions using a physics simulation library.

PubMed

Ueno, Yutaka; Ito, Shuntaro; Konagaya, Akihiko

2014-12-01

To better understand the behaviors and structural dynamics of proteins within a cell, novel software tools are being developed that can create molecular animations based on the findings of structural biology. This study proposes our method developed based on our prototypes to detect collisions and examine the soft-body dynamics of molecular models. The code was implemented with a software development toolkit for rigid-body dynamics simulation and a three-dimensional graphics library. The essential functions of the target software system included the basic molecular modeling environment, collision detection in the molecular models, and physical simulations of the movement of the model. Taking advantage of recent software technologies such as physics simulation modules and interpreted scripting language, the functions required for accurate and meaningful molecular animation were implemented efficiently.

Open Source Molecular Modeling

PubMed Central

Pirhadi, Somayeh; Sunseri, Jocelyn; Koes, David Ryan

2016-01-01

The success of molecular modeling and computational chemistry efforts are, by definition, dependent on quality software applications. Open source software development provides many advantages to users of modeling applications, not the least of which is that the software is free and completely extendable. In this review we categorize, enumerate, and describe available open source software packages for molecular modeling and computational chemistry. PMID:27631126

Quantitative structure-activity relationship of organosulphur compounds as soybean 15-lipoxygenase inhibitors using CoMFA and CoMSIA.

PubMed

Caballero, Julio; Fernández, Michael; Coll, Deysma

2010-12-01

Three-dimensional quantitative structure-activity relationship studies were carried out on a series of 28 organosulphur compounds as 15-lipoxygenase inhibitors using comparative molecular field analysis and comparative molecular similarity indices analysis. Quantitative information on structure-activity relationships is provided for further rational development and direction of selective synthesis. All models were carried out over a training set including 22 compounds. The best comparative molecular field analysis model only included steric field and had a good Q² = 0.789. Comparative molecular similarity indices analysis overcame the comparative molecular field analysis results: the best comparative molecular similarity indices analysis model also only included steric field and had a Q² = 0.894. In addition, this model predicted adequately the compounds contained in the test set. Furthermore, plots of steric comparative molecular similarity indices analysis field allowed conclusions to be drawn for the choice of suitable inhibitors. In this sense, our model should prove useful in future 15-lipoxygenase inhibitor design studies. © 2010 John Wiley & Sons A/S.

Molecular Dynamics implementation of BN2D or 'Mercedes Benz' water model

NASA Astrophysics Data System (ADS)

Scukins, Arturs; Bardik, Vitaliy; Pavlov, Evgen; Nerukh, Dmitry

2015-05-01

Two-dimensional 'Mercedes Benz' (MB) or BN2D water model (Naim, 1971) is implemented in Molecular Dynamics. It is known that the MB model can capture abnormal properties of real water (high heat capacity, minima of pressure and isothermal compressibility, negative thermal expansion coefficient) (Silverstein et al., 1998). In this work formulas for calculating the thermodynamic, structural and dynamic properties in microcanonical (NVE) and isothermal-isobaric (NPT) ensembles for the model from Molecular Dynamics simulation are derived and verified against known Monte Carlo results. The convergence of the thermodynamic properties and the system's numerical stability are investigated. The results qualitatively reproduce the peculiarities of real water making the model a visually convenient tool that also requires less computational resources, thus allowing simulations of large (hydrodynamic scale) molecular systems. We provide the open source code written in C/C++ for the BN2D water model implementation using Molecular Dynamics.

VAMPnets for deep learning of molecular kinetics.

PubMed

Mardt, Andreas; Pasquali, Luca; Wu, Hao; Noé, Frank

2018-01-02

There is an increasing demand for computing the relevant structures, equilibria, and long-timescale kinetics of biomolecular processes, such as protein-drug binding, from high-throughput molecular dynamics simulations. Current methods employ transformation of simulated coordinates into structural features, dimension reduction, clustering the dimension-reduced data, and estimation of a Markov state model or related model of the interconversion rates between molecular structures. This handcrafted approach demands a substantial amount of modeling expertise, as poor decisions at any step will lead to large modeling errors. Here we employ the variational approach for Markov processes (VAMP) to develop a deep learning framework for molecular kinetics using neural networks, dubbed VAMPnets. A VAMPnet encodes the entire mapping from molecular coordinates to Markov states, thus combining the whole data processing pipeline in a single end-to-end framework. Our method performs equally or better than state-of-the-art Markov modeling methods and provides easily interpretable few-state kinetic models.

Lighting the dark molecular gas and a Bok globule

NASA Astrophysics Data System (ADS)

Togi, Aditya G.

Stars are the building blocks of galaxies. The gas present in galaxies is the primary fuel for star formation. Galaxy evolution depends on the amount of gas present in the interstellar medium (ISM). Stars are born mainly from molecular gas in the GMCs. Robust knowledge of the molecular hydrogen H2 gas distribution is necessary to understand star formation in galaxies. Since H2 is not readily observable in the cold interstellar medium (ISM), the molecular gas content has traditionally been inferred using indirect tracers like carbon-monoxide (CO), dust emission, gamma ray interactions, and star formation efficiency. Physical processes resulting in enhancement and reduction of these indirect tracers can result in misleading estimates of molecular gas masses. My dissertation work is based on devising a new temperature power law distribution model for H2, a direct tracer, to calculate the total molecular gas mass in galaxies. The model parameters are estimated using mid infrared (MIR) H2 rotational line fluxes obtained from IRS-Spitzer (Infrared Spectrograph-Spitzer) instrument and the model is extrapolated to a suitable lower temperature to recover the total molecular gas mass. The power law model is able to recover the dark molecular gas, undetected by CO, in galaxies at metallicity as low as one-tenth of our Milky Way value. I have applied the power law model in U/LIRGs and shocks of Stephan's Quintet to understand molecular gas properties, where shocks play an important role in exciting H2. Comparing the molecular gas content derived through our power law model can be useful in studying the application of our model in mergers. The parameters derived by our model is useful in understanding variation in molecular gas properties in shock regions of Stephan's Quintet. Low mass stars are formed in small isolated dense cores known as Bok globules. Multiple star formation events are seen in a Bok globule. In my thesis I also studied a Bok globule, B207, and determined the physical properties and future evolutionary stage of the cloud. My thesis spans studying ISM properties in galaxies from kpc to sub-pc scales. Using the power law model in the coming era of James Webb Space Telescope (JWST) with the high sensitivity MIR Instrument (MIRI) spectrograph we will be able to understand the properties of molecular gas at low and high redshifts.

MOlecular MAterials Property Prediction Package (MOMAP) 1.0: a software package for predicting the luminescent properties and mobility of organic functional materials

NASA Astrophysics Data System (ADS)

Niu, Yingli; Li, Wenqiang; Peng, Qian; Geng, Hua; Yi, Yuanping; Wang, Linjun; Nan, Guangjun; Wang, Dong; Shuai, Zhigang

2018-04-01

MOlecular MAterials Property Prediction Package (MOMAP) is a software toolkit for molecular materials property prediction. It focuses on luminescent properties and charge mobility properties. This article contains a brief descriptive introduction of key features, theoretical models and algorithms of the software, together with examples that illustrate the performance. First, we present the theoretical models and algorithms for molecular luminescent properties calculation, which includes the excited-state radiative/non-radiative decay rate constant and the optical spectra. Then, a multi-scale simulation approach and its algorithm for the molecular charge mobility are described. This approach is based on hopping model and combines with Kinetic Monte Carlo and molecular dynamics simulations, and it is especially applicable for describing a large category of organic semiconductors, whose inter-molecular electronic coupling is much smaller than intra-molecular charge reorganisation energy.

A Comparative Study of Successful Central Nervous System Drugs Using Molecular Modeling

ERIC Educational Resources Information Center

Kim, Hyosub; Sulaimon, Segun; Menezes, Sandra; Son, Anne; Menezes, Warren J. C.

2011-01-01

Molecular modeling is a powerful tool used for three-dimensional visualization and for exploring electrostatic forces involved in drug transport. This tool enhances student understanding of structure-property relationships, as well as actively engaging them in class. Molecular modeling of several central nervous system (CNS) drugs is used to…

Assessing High School Chemistry Students' Modeling Sub-Skills in a Computerized Molecular Modeling Learning Environment

ERIC Educational Resources Information Center

Dori, Yehudit Judy; Kaberman, Zvia

2012-01-01

Much knowledge in chemistry exists at a molecular level, inaccessible to direct perception. Chemistry instruction should therefore include multiple visual representations, such as molecular models and symbols. This study describes the implementation and assessment of a learning unit designed for 12th grade chemistry honors students. The organic…

Digital Learning Material for Model Building in Molecular Biology

ERIC Educational Resources Information Center

Aegerter-Wilmsen, Tinri; Janssen, Fred; Hartog, Rob; Bisseling, Ton

2005-01-01

Building models to describe processes forms an essential part of molecular biology research. However, in molecular biology curricula little attention is generally being paid to the development of this skill. In order to provide students the opportunity to improve their model building skills, we decided to develop a number of digital cases about…

Phase Structure of Strong-Field Tunneling Wave Packets from Molecules.

PubMed

Liu, Ming-Ming; Li, Min; Wu, Chengyin; Gong, Qihuang; Staudte, André; Liu, Yunquan

2016-04-22

We study the phase structure of the tunneling wave packets from strong-field ionization of molecules and present a molecular quantum-trajectory Monte Carlo model to describe the laser-driven dynamics of photoelectron momentum distributions of molecules. Using our model, we reproduce and explain the alignment-dependent molecular frame photoelectron spectra of strong-field tunneling ionization of N_{2} reported by M. Meckel et al. [Nat. Phys. 10, 594 (2014)]. In addition to modeling the low-energy photoelectron angular distributions quantitatively, we extract the phase structure of strong-field molecular tunneling wave packets, shedding light on its physical origin. The initial phase of the tunneling wave packets at the tunnel exit depends on both the initial transverse momentum distribution and the molecular internuclear distance. We further show that the ionizing molecular orbital has a critical effect on the initial phase of the tunneling wave packets. The phase structure of the photoelectron wave packet is a key ingredient for modeling strong-field molecular photoelectron holography, high-harmonic generation, and molecular orbital imaging.

3D-Lab: a collaborative web-based platform for molecular modeling.

PubMed

Grebner, Christoph; Norrby, Magnus; Enström, Jonatan; Nilsson, Ingemar; Hogner, Anders; Henriksson, Jonas; Westin, Johan; Faramarzi, Farzad; Werner, Philip; Boström, Jonas

2016-09-01

The use of 3D information has shown impact in numerous applications in drug design. However, it is often under-utilized and traditionally limited to specialists. We want to change that, and present an approach making 3D information and molecular modeling accessible and easy-to-use 'for the people'. A user-friendly and collaborative web-based platform (3D-Lab) for 3D modeling, including a blazingly fast virtual screening capability, was developed. 3D-Lab provides an interface to automatic molecular modeling, like conformer generation, ligand alignments, molecular dockings and simple quantum chemistry protocols. 3D-Lab is designed to be modular, and to facilitate sharing of 3D-information to promote interactions between drug designers. Recent enhancements to our open-source virtual reality tool Molecular Rift are described. The integrated drug-design platform allows drug designers to instantaneously access 3D information and readily apply advanced and automated 3D molecular modeling tasks, with the aim to improve decision-making in drug design projects.

Molecular modeling: An open invitation for applied mathematics

NASA Astrophysics Data System (ADS)

Mezey, Paul G.

2013-10-01

Molecular modeling methods provide a very wide range of challenges for innovative mathematical and computational techniques, where often high dimensionality, large sets of data, and complicated interrelations imply a multitude of iterative approximations. The physical and chemical basis of these methodologies involves quantum mechanics with several non-intuitive aspects, where classical interpretation and classical analogies are often misleading or outright wrong. Hence, instead of the everyday, common sense approaches which work so well in engineering, in molecular modeling one often needs to rely on rather abstract mathematical constraints and conditions, again emphasizing the high level of reliance on applied mathematics. Yet, the interdisciplinary aspects of the field of molecular modeling also generates some inertia and perhaps too conservative reliance on tried and tested methodologies, that is at least partially caused by the less than up-to-date involvement in the newest developments in applied mathematics. It is expected that as more applied mathematicians take up the challenge of employing the latest advances of their field in molecular modeling, important breakthroughs may follow. In this presentation some of the current challenges of molecular modeling are discussed.

The cognitive life of mechanical molecular models.

PubMed

Charbonneau, Mathieu

2013-12-01

The use of physical models of molecular structures as research tools has been central to the development of biochemistry and molecular biology. Intriguingly, it has received little attention from scholars of science. In this paper, I argue that these physical models are not mere three-dimensional representations but that they are in fact very special research tools: they are cognitive augmentations. Despite the fact that they are external props, these models serve as cognitive tools that augment and extend the modeler's cognitive capacities and performance in molecular modeling tasks. This cognitive enhancement is obtained because of the way the modeler interacts with these models, the models' materiality contributing to the solving of the molecule's structure. Furthermore, I argue that these material models and their component parts were designed, built and used specifically to serve as cognitive facilitators and cognitive augmentations. Copyright © 2013 Elsevier Ltd. All rights reserved.

Discovery of an Unexplored Protein Structural Scaffold of Serine Protease from Big Blue Octopus (Octopus cyanea): A New Prospective Lead Molecule.

PubMed

Panda, Subhamay; Kumari, Leena

2017-01-01

Serine proteases are a group of enzymes that hydrolyses the peptide bonds in proteins. In mammals, these enzymes help in the regulation of several major physiological functions such as digestion, blood clotting, responses of immune system, reproductive functions and the complement system. Serine proteases obtained from the venom of Octopodidae family is a relatively unexplored area of research. In the present work, we tried to effectively utilize comparative composite molecular modeling technique. Our key aim was to propose the first molecular model structure of unexplored serine protease 5 derived from big blue octopus. The other objective of this study was to analyze the distribution of negatively and positively charged amino acid over molecular modeled structure, distribution of secondary structural elements, hydrophobicity molecular surface analysis and electrostatic potential analysis with the aid of different bioinformatic tools. In the present study, molecular model has been generated with the help of I-TASSER suite. Afterwards the refined structural model was validated with standard methods. For functional annotation of protein molecule we used Protein Information Resource (PIR) database. Serine protease 5 of big blue octopus was analyzed with different bioinformatical algorithms for the distribution of negatively and positively charged amino acid over molecular modeled structure, distribution of secondary structural elements, hydrophobicity molecular surface analysis and electrostatic potential analysis. The functionally critical amino acids and ligand- binding site (LBS) of the proteins (modeled) were determined using the COACH program. The molecular model data in cooperation to other pertinent post model analysis data put forward molecular insight to proteolytic activity of serine protease 5, which helps in the clear understanding of procoagulant and anticoagulant characteristics of this natural lead molecule. Our approach was to investigate the octopus venom protein as a whole or a part of their structure that may result in the development of new lead molecule. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

GPU-Accelerated Molecular Modeling Coming Of Age

PubMed Central

Stone, John E.; Hardy, David J.; Ufimtsev, Ivan S.

2010-01-01

Graphics processing units (GPUs) have traditionally been used in molecular modeling solely for visualization of molecular structures and animation of trajectories resulting from molecular dynamics simulations. Modern GPUs have evolved into fully programmable, massively parallel co-processors that can now be exploited to accelerate many scientific computations, typically providing about one order of magnitude speedup over CPU code and in special cases providing speedups of two orders of magnitude. This paper surveys the development of molecular modeling algorithms that leverage GPU computing, the advances already made and remaining issues to be resolved, and the continuing evolution of GPU technology that promises to become even more useful to molecular modeling. Hardware acceleration with commodity GPUs is expected to benefit the overall computational biology community by bringing teraflops performance to desktop workstations and in some cases potentially changing what were formerly batch-mode computational jobs into interactive tasks. PMID:20675161

GPU-accelerated molecular modeling coming of age.

PubMed

Stone, John E; Hardy, David J; Ufimtsev, Ivan S; Schulten, Klaus

2010-09-01

Graphics processing units (GPUs) have traditionally been used in molecular modeling solely for visualization of molecular structures and animation of trajectories resulting from molecular dynamics simulations. Modern GPUs have evolved into fully programmable, massively parallel co-processors that can now be exploited to accelerate many scientific computations, typically providing about one order of magnitude speedup over CPU code and in special cases providing speedups of two orders of magnitude. This paper surveys the development of molecular modeling algorithms that leverage GPU computing, the advances already made and remaining issues to be resolved, and the continuing evolution of GPU technology that promises to become even more useful to molecular modeling. Hardware acceleration with commodity GPUs is expected to benefit the overall computational biology community by bringing teraflops performance to desktop workstations and in some cases potentially changing what were formerly batch-mode computational jobs into interactive tasks. (c) 2010 Elsevier Inc. All rights reserved.

Coarse-grained molecular dynamics simulations for giant protein-DNA complexes

NASA Astrophysics Data System (ADS)

Takada, Shoji

Biomolecules are highly hierarchic and intrinsically flexible. Thus, computational modeling calls for multi-scale methodologies. We have been developing a coarse-grained biomolecular model where on-average 10-20 atoms are grouped into one coarse-grained (CG) particle. Interactions among CG particles are tuned based on atomistic interactions and the fluctuation matching algorithm. CG molecular dynamics methods enable us to simulate much longer time scale motions of much larger molecular systems than fully atomistic models. After broad sampling of structures with CG models, we can easily reconstruct atomistic models, from which one can continue conventional molecular dynamics simulations if desired. Here, we describe our CG modeling methodology for protein-DNA complexes, together with various biological applications, such as the DNA duplication initiation complex, model chromatins, and transcription factor dynamics on chromatin-like environment.

Panel 4: Recent Advances in Otitis Media in Molecular Biology, Biochemistry, Genetics, and Animal Models

PubMed Central

Li, Jian-Dong; Hermansson, Ann; Ryan, Allen F.; Bakaletz, Lauren O.; Brown, Steve D.; Cheeseman, Michael T.; Juhn, Steven K.; Jung, Timothy T. K.; Lim, David J.; Lim, Jae Hyang; Lin, Jizhen; Moon, Sung-Kyun; Post, J. Christopher

2014-01-01

Background Otitis media (OM) is the most common childhood bacterial infection and also the leading cause of conductive hearing loss in children. Currently, there is an urgent need for developing novel therapeutic agents for treating OM based on full understanding of molecular pathogenesis in the areas of molecular biology, biochemistry, genetics, and animal model studies in OM. Objective To provide a state-of-the-art review concerning recent advances in OM in the areas of molecular biology, biochemistry, genetics, and animal model studies and to discuss the future directions of OM studies in these areas. Data Sources and Review Methods A structured search of the current literature (since June 2007). The authors searched PubMed for published literature in the areas of molecular biology, biochemistry, genetics, and animal model studies in OM. Results Over the past 4 years, significant progress has been made in the areas of molecular biology, biochemistry, genetics, and animal model studies in OM. These studies brought new insights into our understanding of the molecular and biochemical mechanisms underlying the molecular pathogenesis of OM and helped identify novel therapeutic targets for OM. Conclusions and Implications for Practice Our understanding of the molecular pathogenesis of OM has been significantly advanced, particularly in the areas of inflammation, innate immunity, mucus overproduction, mucosal hyperplasia, middle ear and inner ear interaction, genetics, genome sequencing, and animal model studies. Although these studies are still in their experimental stages, they help identify new potential therapeutic targets. Future preclinical and clinical studies will help to translate these exciting experimental research findings into clinical applications. PMID:23536532

A Model of How Different Biology Experts Explain Molecular and Cellular Mechanisms

ERIC Educational Resources Information Center

Trujillo, Caleb M.; Anderson, Trevor R.; Pelaez, Nancy J.

2015-01-01

Constructing explanations is an essential skill for all science learners. The goal of this project was to model the key components of expert explanation of molecular and cellular mechanisms. As such, we asked: What is an appropriate model of the components of explanation used by biology experts to explain molecular and cellular mechanisms? Do…

A collaborative molecular modeling environment using a virtual tunneling service.

PubMed

Lee, Jun; Kim, Jee-In; Kang, Lin-Woo

2012-01-01

Collaborative researches of three-dimensional molecular modeling can be limited by different time zones and locations. A networked virtual environment can be utilized to overcome the problem caused by the temporal and spatial differences. However, traditional approaches did not sufficiently consider integration of different computing environments, which were characterized by types of applications, roles of users, and so on. We propose a collaborative molecular modeling environment to integrate different molecule modeling systems using a virtual tunneling service. We integrated Co-Coot, which is a collaborative crystallographic object-oriented toolkit, with VRMMS, which is a virtual reality molecular modeling system, through a collaborative tunneling system. The proposed system showed reliable quantitative and qualitative results through pilot experiments.

Informing Mechanistic Toxicology with Computational Molecular Models

EPA Science Inventory

Computational molecular models of chemicals interacting with biomolecular targets provides toxicologists a valuable, affordable, and sustainable source of in silico molecular level information that augments, enriches, and complements in vitro and in vivo effo...

Assessment of PDF Micromixing Models Using DNS Data for a Two-Step Reaction

NASA Astrophysics Data System (ADS)

Tsai, Kuochen; Chakrabarti, Mitali; Fox, Rodney O.; Hill, James C.

1996-11-01

Although the probability density function (PDF) method is known to treat the chemical reaction terms exactly, its application to turbulent reacting flows have been overshadowed by the ability to model the molecular mixing terms satisfactorily. In this study, two PDF molecular mixing models, the linear-mean-square-estimation (LMSE or IEM) model and the generalized interaction-by-exchange-with-the-mean (GIEM) model, are compared with the DNS data in decaying turbulence with a two-step parallel-consecutive reaction and two segregated initial conditions: ``slabs" and ``blobs". Since the molecular mixing model is expected to have a strong effect on the mean values of chemical species under such initial conditions, the model evaluation is intended to answer the following questions: Can the PDF models predict the mean values of chemical species correctly with completely segregated initial conditions? (2) Is a single molecular mixing timescale sufficient for the PDF models to predict the mean values with different initial conditions? (3) Will the chemical reactions change the molecular mixing timescales of the reacting species enough to affect the accuracy of the model's prediction for the mean values of chemical species?

Simultaneous construction of PCR-DGGE-based predictive models of Listeria monocytogenes and Vibrio parahaemolyticus on cooked shrimps.

PubMed

Liao, C; Peng, Z Y; Li, J B; Cui, X W; Zhang, Z H; Malakar, P K; Zhang, W J; Pan, Y J; Zhao, Y

2015-03-01

The aim of this study was to simultaneously construct PCR-DGGE-based predictive models of Listeria monocytogenes and Vibrio parahaemolyticus on cooked shrimps at 4 and 10°C. Calibration curves were established to correlate peak density of DGGE bands with microbial counts. Microbial counts derived from PCR-DGGE and plate methods were fitted by Baranyi model to obtain molecular and traditional predictive models. For L. monocytogenes, growing at 4 and 10°C, molecular predictive models were constructed. It showed good evaluations of correlation coefficients (R(2) > 0.92), bias factors (Bf ) and accuracy factors (Af ) (1.0 ≤ Bf ≤ Af ≤ 1.1). Moreover, no significant difference was found between molecular and traditional predictive models when analysed on lag phase (λ), maximum growth rate (μmax ) and growth data (P > 0.05). But for V. parahaemolyticus, inactivated at 4 and 10°C, molecular models show significant difference when compared with traditional models. Taken together, these results suggest that PCR-DGGE based on DNA can be used to construct growth models, but it is inappropriate for inactivation models yet. This is the first report of developing PCR-DGGE to simultaneously construct multiple molecular models. It has been known for a long time that microbial predictive models based on traditional plate methods are time-consuming and labour-intensive. Denaturing gradient gel electrophoresis (DGGE) has been widely used as a semiquantitative method to describe complex microbial community. In our study, we developed DGGE to quantify bacterial counts and simultaneously established two molecular predictive models to describe the growth and survival of two bacteria (Listeria monocytogenes and Vibrio parahaemolyticus) at 4 and 10°C. We demonstrated that PCR-DGGE could be used to construct growth models. This work provides a new approach to construct molecular predictive models and thereby facilitates predictive microbiology and QMRA (Quantitative Microbial Risk Assessment). © 2014 The Society for Applied Microbiology.

Experimental and Numerical Analysis of Narrowband Coherent Rayleigh-Brillouin Scattering in Atomic and Molecular Species (Pre Print)

DTIC Science & Technology

2012-02-01

use of polar gas species. While current simplified models have adequately predicted CRS and CRBS line shapes for a wide variety of cases, multiple ...published simplified models are presented for argon, molecular nitrogen, and methane at 300 & 500 K and 1 atm. The simplified models require uncertain gas... models are presented for argon, molecular nitrogen, and methane at 300 & 500 K and 1 atm. The simplified models require uncertain gas properties

Molecular weight kinetics and chain scission models for dextran polymers during ultrasonic degradation.

PubMed

Pu, Yuanyuan; Zou, Qingsong; Hou, Dianzhi; Zhang, Yiping; Chen, Shan

2017-01-20

Ultrasonic degradation of six dextran samples with different initial molecular weights (IMW) has been performed to investigate the degradation behavior and chain scission mechanism of dextrans. The weight-average molecular weight (Mw) and polydispersity index (D value) were monitored by High Performance Gel Permeation Chromatography (HPGPC). Results showed that Mw and D value decreased with increasing ultrasonic time, resulting in a more homologous dextran solution with lower molecular weight. A significant degradation occurred in dextrans with higher IMW, particularly at the initial stage of the ultrasonic treatment. The Malhotra model was found to well describe the molecular weight kinetics for all dextran samples. Experimental data was fitted into two chain scission models to study dextran chain scission mechanism and the model performance was compared. Results indicated that the midpoint scission model agreed well with experimental results, with a linear regression factor of R 2 >0.99. Copyright © 2016 Elsevier Ltd. All rights reserved.

Ergodicity and model quality in template-restrained canonical and temperature/Hamiltonian replica exchange coarse-grained molecular dynamics simulations of proteins.

PubMed

Karczyńska, Agnieszka S; Czaplewski, Cezary; Krupa, Paweł; Mozolewska, Magdalena A; Joo, Keehyoung; Lee, Jooyoung; Liwo, Adam

2017-12-05

Molecular simulations restrained to single or multiple templates are commonly used in protein-structure modeling. However, the restraints introduce additional barriers, thus impairing the ergodicity of simulations, which can affect the quality of the resulting models. In this work, the effect of restraint types and simulation schemes on ergodicity and model quality was investigated by performing template-restrained canonical molecular dynamics (MD), multiplexed replica-exchange molecular dynamics, and Hamiltonian replica exchange molecular dynamics (HREMD) simulations with the coarse-grained UNRES force field on nine selected proteins, with pseudo-harmonic log-Gaussian (unbounded) or Lorentzian (bounded) restraint functions. The best ergodicity was exhibited by HREMD. It has been found that non-ergodicity does not affect model quality if good templates are used to generate restraints. However, when poor-quality restraints not covering the entire protein are used, the improved ergodicity of HREMD can lead to significantly improved protein models. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Direct Air Capture of CO2 with an Amine Resin: A Molecular Modeling Study of the CO2 Capturing Process

PubMed Central

2017-01-01

Several reactions, known from other amine systems for CO2 capture, have been proposed for Lewatit R VP OC 1065. The aim of this molecular modeling study is to elucidate the CO2 capture process: the physisorption process prior to the CO2-capture and the reactions. Molecular modeling yields that the resin has a structure with benzyl amine groups on alternating positions in close vicinity of each other. Based on this structure, the preferred adsorption mode of CO2 and H2O was established. Next, using standard Density Functional Theory two catalytic reactions responsible for the actual CO2 capture were identified: direct amine and amine-H2O catalyzed formation of carbamic acid. The latter is a new type of catalysis. Other reactions are unlikely. Quantitative verification of the molecular modeling results with known experimental CO2 adsorption isotherms, applying a dual site Langmuir adsorption isotherm model, further supports all results of this molecular modeling study. PMID:29142339

Molecular dynamics simulations of biological membranes and membrane proteins using enhanced conformational sampling algorithms☆

PubMed Central

Mori, Takaharu; Miyashita, Naoyuki; Im, Wonpil; Feig, Michael; Sugita, Yuji

2016-01-01

This paper reviews various enhanced conformational sampling methods and explicit/implicit solvent/membrane models, as well as their recent applications to the exploration of the structure and dynamics of membranes and membrane proteins. Molecular dynamics simulations have become an essential tool to investigate biological problems, and their success relies on proper molecular models together with efficient conformational sampling methods. The implicit representation of solvent/membrane environments is reasonable approximation to the explicit all-atom models, considering the balance between computational cost and simulation accuracy. Implicit models can be easily combined with replica-exchange molecular dynamics methods to explore a wider conformational space of a protein. Other molecular models and enhanced conformational sampling methods are also briefly discussed. As application examples, we introduce recent simulation studies of glycophorin A, phospholamban, amyloid precursor protein, and mixed lipid bilayers and discuss the accuracy and efficiency of each simulation model and method. This article is part of a Special Issue entitled: Membrane Proteins. Guest Editors: J.C. Gumbart and Sergei Noskov. PMID:26766517

Mark R. Nimlos | NREL

Science.gov Websites

, reaction kinetics, computational modeling, photochemistry, and molecular spectroscopy. Nimlos has served as Chemical reaction energetics and kinetics Biomass pyrolysis and gasification Heterogeneous catalysis in zeolites Quantum modeling and kinetic modeling of reaction Molecular dynamics modeling

Constructing Molecular Models with Low-Cost Toy Beads

ERIC Educational Resources Information Center

Ng, Pun-hon; Wong, Siu-ling; Mak, Se-yuen

2012-01-01

In teaching the science of the nano world, ball-and-stick molecular models are frequently used as 3D representations of molecules. Unlike a chemical formula, a molecular model allows us to visualise the 3D shape of the molecule and the relative positions of its atoms, the bonds between atoms and why a pair of mirror isomers with the same atoms,…

Modeling Stochastic Kinetics of Molecular Machines at Multiple Levels: From Molecules to Modules

PubMed Central

Chowdhury, Debashish

2013-01-01

A molecular machine is either a single macromolecule or a macromolecular complex. In spite of the striking superficial similarities between these natural nanomachines and their man-made macroscopic counterparts, there are crucial differences. Molecular machines in a living cell operate stochastically in an isothermal environment far from thermodynamic equilibrium. In this mini-review we present a catalog of the molecular machines and an inventory of the essential toolbox for theoretically modeling these machines. The tool kits include 1), nonequilibrium statistical-physics techniques for modeling machines and machine-driven processes; and 2), statistical-inference methods for reverse engineering a functional machine from the empirical data. The cell is often likened to a microfactory in which the machineries are organized in modular fashion; each module consists of strongly coupled multiple machines, but different modules interact weakly with each other. This microfactory has its own automated supply chain and delivery system. Buoyed by the success achieved in modeling individual molecular machines, we advocate integration of these models in the near future to develop models of functional modules. A system-level description of the cell from the perspective of molecular machinery (the mechanome) is likely to emerge from further integrations that we envisage here. PMID:23746505

Transitioning NWChem to the Next Generation of Manycore Machines

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

Bylaska, Eric J.; Apra, E; Kowalski, Karol

The NorthWest chemistry (NWChem) modeling software is a popular molecular chemistry simulation software that was designed from the start to work on massively parallel processing supercomputers [1-3]. It contains an umbrella of modules that today includes self-consistent eld (SCF), second order Møller-Plesset perturbation theory (MP2), coupled cluster (CC), multiconguration self-consistent eld (MCSCF), selected conguration interaction (CI), tensor contraction engine (TCE) many body methods, density functional theory (DFT), time-dependent density functional theory (TDDFT), real-time time-dependent density functional theory, pseudopotential plane-wave density functional theory (PSPW), band structure (BAND), ab initio molecular dynamics (AIMD), Car-Parrinello molecular dynamics (MD), classical MD, hybrid quantum mechanicsmore » molecular mechanics (QM/MM), hybrid ab initio molecular dynamics molecular mechanics (AIMD/MM), gauge independent atomic orbital nuclear magnetic resonance (GIAO NMR), conductor like screening solvation model (COSMO), conductor-like screening solvation model based on density (COSMO-SMD), and reference interaction site model (RISM) solvation models, free energy simulations, reaction path optimization, parallel in time, among other capabilities [4]. Moreover, new capabilities continue to be added with each new release.« less

Cellular automata with object-oriented features for parallel molecular network modeling.

PubMed

Zhu, Hao; Wu, Yinghui; Huang, Sui; Sun, Yan; Dhar, Pawan

2005-06-01

Cellular automata are an important modeling paradigm for studying the dynamics of large, parallel systems composed of multiple, interacting components. However, to model biological systems, cellular automata need to be extended beyond the large-scale parallelism and intensive communication in order to capture two fundamental properties characteristic of complex biological systems: hierarchy and heterogeneity. This paper proposes extensions to a cellular automata language, Cellang, to meet this purpose. The extended language, with object-oriented features, can be used to describe the structure and activity of parallel molecular networks within cells. Capabilities of this new programming language include object structure to define molecular programs within a cell, floating-point data type and mathematical functions to perform quantitative computation, message passing capability to describe molecular interactions, as well as new operators, statements, and built-in functions. We discuss relevant programming issues of these features, including the object-oriented description of molecular interactions with molecule encapsulation, message passing, and the description of heterogeneity and anisotropy at the cell and molecule levels. By enabling the integration of modeling at the molecular level with system behavior at cell, tissue, organ, or even organism levels, the program will help improve our understanding of how complex and dynamic biological activities are generated and controlled by parallel functioning of molecular networks. Index Terms-Cellular automata, modeling, molecular network, object-oriented.

Computational Materials Research

NASA Technical Reports Server (NTRS)

Hinkley, Jeffrey A. (Editor); Gates, Thomas S. (Editor)

1996-01-01

Computational Materials aims to model and predict thermodynamic, mechanical, and transport properties of polymer matrix composites. This workshop, the second coordinated by NASA Langley, reports progress in measurements and modeling at a number of length scales: atomic, molecular, nano, and continuum. Assembled here are presentations on quantum calculations for force field development, molecular mechanics of interfaces, molecular weight effects on mechanical properties, molecular dynamics applied to poling of polymers for electrets, Monte Carlo simulation of aromatic thermoplastics, thermal pressure coefficients of liquids, ultrasonic elastic constants, group additivity predictions, bulk constitutive models, and viscoplasticity characterization.

Computer-aided molecular modeling techniques for predicting the stability of drug cyclodextrin inclusion complexes in aqueous solutions

NASA Astrophysics Data System (ADS)

Faucci, Maria Teresa; Melani, Fabrizio; Mura, Paola

2002-06-01

Molecular modeling was used to investigate factors influencing complex formation between cyclodextrins and guest molecules and predict their stability through a theoretical model based on the search for a correlation between experimental stability constants ( Ks) and some theoretical parameters describing complexation (docking energy, host-guest contact surfaces, intermolecular interaction fields) calculated from complex structures at a minimum conformational energy, obtained through stochastic methods based on molecular dynamic simulations. Naproxen, ibuprofen, ketoprofen and ibuproxam were used as model drug molecules. Multiple Regression Analysis allowed identification of the significant factors for the complex stability. A mathematical model ( r=0.897) related log Ks with complex docking energy and lipophilic molecular fields of cyclodextrin and drug.

A Collaborative Molecular Modeling Environment Using a Virtual Tunneling Service

PubMed Central

Lee, Jun; Kim, Jee-In; Kang, Lin-Woo

2012-01-01

Collaborative researches of three-dimensional molecular modeling can be limited by different time zones and locations. A networked virtual environment can be utilized to overcome the problem caused by the temporal and spatial differences. However, traditional approaches did not sufficiently consider integration of different computing environments, which were characterized by types of applications, roles of users, and so on. We propose a collaborative molecular modeling environment to integrate different molecule modeling systems using a virtual tunneling service. We integrated Co-Coot, which is a collaborative crystallographic object-oriented toolkit, with VRMMS, which is a virtual reality molecular modeling system, through a collaborative tunneling system. The proposed system showed reliable quantitative and qualitative results through pilot experiments. PMID:22927721

Magnetohydrodynamic Models of Molecular Tornadoes

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

Au, Kelvin; Fiege, Jason D., E-mail: fiege@physics.umanitoba.ca

Recent observations near the Galactic Center (GC) have found several molecular filaments displaying striking helically wound morphology that are collectively known as molecular tornadoes. We investigate the equilibrium structure of these molecular tornadoes by formulating a magnetohydrodynamic model of a rotating, helically magnetized filament. A special analytical solution is derived where centrifugal forces balance exactly with toroidal magnetic stress. From the physics of torsional Alfvén waves we derive a constraint that links the toroidal flux-to-mass ratio and the pitch angle of the helical field to the rotation laws, which we find to be an important component in describing the molecularmore » tornado structure. The models are compared to the Ostriker solution for isothermal, nonmagnetic, nonrotating filaments. We find that neither the analytic model nor the Alfvén wave model suffer from the unphysical density inversions noted by other authors. A Monte Carlo exploration of our parameter space is constrained by observational measurements of the Pigtail Molecular Cloud, the Double Helix Nebula, and the GC Molecular Tornado. Observable properties such as the velocity dispersion, filament radius, linear mass, and surface pressure can be used to derive three dimensionless constraints for our dimensionless models of these three objects. A virial analysis of these constrained models is studied for these three molecular tornadoes. We find that self-gravity is relatively unimportant, whereas magnetic fields and external pressure play a dominant role in the confinement and equilibrium radial structure of these objects.« less

Prediction of Sliding Friction Coefficient Based on a Novel Hybrid Molecular-Mechanical Model.

PubMed

Zhang, Xiaogang; Zhang, Yali; Wang, Jianmei; Sheng, Chenxing; Li, Zhixiong

2018-08-01

Sliding friction is a complex phenomenon which arises from the mechanical and molecular interactions of asperities when examined in a microscale. To reveal and further understand the effects of micro scaled mechanical and molecular components of friction coefficient on overall frictional behavior, a hybrid molecular-mechanical model is developed to investigate the effects of main factors, including different loads and surface roughness values, on the sliding friction coefficient in a boundary lubrication condition. Numerical modelling was conducted using a deterministic contact model and based on the molecular-mechanical theory of friction. In the contact model, with given external loads and surface topographies, the pressure distribution, real contact area, and elastic/plastic deformation of each single asperity contact were calculated. Then asperity friction coefficient was predicted by the sum of mechanical and molecular components of friction coefficient. The mechanical component was mainly determined by the contact width and elastic/plastic deformation, and the molecular component was estimated as a function of the contact area and interfacial shear stress. Numerical results were compared with experimental results and a good agreement was obtained. The model was then used to predict friction coefficients in different operating and surface conditions. Numerical results explain why applied load has a minimum effect on the friction coefficients. They also provide insight into the effect of surface roughness on the mechanical and molecular components of friction coefficients. It is revealed that the mechanical component dominates the friction coefficient when the surface roughness is large (Rq > 0.2 μm), while the friction coefficient is mainly determined by the molecular component when the surface is relatively smooth (Rq < 0.2 μm). Furthermore, optimal roughness values for minimizing the friction coefficient are recommended.

Capillary Rise: Validity of the Dynamic Contact Angle Models.

PubMed

Wu, Pingkeng; Nikolov, Alex D; Wasan, Darsh T

2017-08-15

The classical Lucas-Washburn-Rideal (LWR) equation, using the equilibrium contact angle, predicts a faster capillary rise process than experiments in many cases. The major contributor to the faster prediction is believed to be the velocity dependent dynamic contact angle. In this work, we investigated the dynamic contact angle models for their ability to correct the dynamic contact angle effect in the capillary rise process. We conducted capillary rise experiments of various wetting liquids in borosilicate glass capillaries and compared the model predictions with our experimental data. The results show that the LWR equations modified by the molecular kinetic theory and hydrodynamic model provide good predictions on the capillary rise of all the testing liquids with fitting parameters, while the one modified by Joos' empirical equation works for specific liquids, such as silicone oils. The LWR equation modified by molecular self-layering model predicts well the capillary rise of carbon tetrachloride, octamethylcyclotetrasiloxane, and n-alkanes with the molecular diameter or measured solvation force data. The molecular self-layering model modified LWR equation also has good predictions on the capillary rise of silicone oils covering a wide range of bulk viscosities with the same key parameter W(0), which results from the molecular self-layering. The advantage of the molecular self-layering model over the other models reveals the importance of the layered molecularly thin wetting film ahead of the main meniscus in the energy dissipation associated with dynamic contact angle. The analysis of the capillary rise of silicone oils with a wide range of bulk viscosities provides new insights into the capillary dynamics of polymer melts.

Degradation mechanisms of bioresorbable polyesters. Part 2. Effects of initial molecular weight and residual monomer.

PubMed

Gleadall, Andrew; Pan, Jingzhe; Kruft, Marc-Anton; Kellomäki, Minna

2014-05-01

This paper presents an understanding of how initial molecular weight and initial monomer fraction affect the degradation of bioresorbable polymers in terms of the underlying hydrolysis mechanisms. A mathematical model was used to analyse the effects of initial molecular weight for various hydrolysis mechanisms including noncatalytic random scission, autocatalytic random scission, noncatalytic end scission or autocatalytic end scission. Different behaviours were identified to relate initial molecular weight to the molecular weight half-life and to the time until the onset of mass loss. The behaviours were validated by fitting the model to experimental data for molecular weight reduction and mass loss of samples with different initial molecular weights. Several publications that consider initial molecular weight were reviewed. The effect of residual monomer on degradation was also analysed, and shown to accelerate the reduction of molecular weight and mass loss. An inverse square root law relationship was found between molecular weight half-life and initial monomer fraction for autocatalytic hydrolysis. The relationship was tested by fitting the model to experimental data with various residual monomer contents. Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Combined Molecular Dynamics Simulation-Molecular-Thermodynamic Theory Framework for Predicting Surface Tensions.

PubMed

Sresht, Vishnu; Lewandowski, Eric P; Blankschtein, Daniel; Jusufi, Arben

2017-08-22

A molecular modeling approach is presented with a focus on quantitative predictions of the surface tension of aqueous surfactant solutions. The approach combines classical Molecular Dynamics (MD) simulations with a molecular-thermodynamic theory (MTT) [ Y. J. Nikas, S. Puvvada, D. Blankschtein, Langmuir 1992 , 8 , 2680 ]. The MD component is used to calculate thermodynamic and molecular parameters that are needed in the MTT model to determine the surface tension isotherm. The MD/MTT approach provides the important link between the surfactant bulk concentration, the experimental control parameter, and the surfactant surface concentration, the MD control parameter. We demonstrate the capability of the MD/MTT modeling approach on nonionic alkyl polyethylene glycol surfactants at the air-water interface and observe reasonable agreement of the predicted surface tensions and the experimental surface tension data over a wide range of surfactant concentrations below the critical micelle concentration. Our modeling approach can be extended to ionic surfactants and their mixtures with both ionic and nonionic surfactants at liquid-liquid interfaces.

Diffusion-controlled interface kinetics-inclusive system-theoretic propagation models for molecular communication systems

NASA Astrophysics Data System (ADS)

Chude-Okonkwo, Uche A. K.; Malekian, Reza; Maharaj, B. T.

2015-12-01

Inspired by biological systems, molecular communication has been proposed as a new communication paradigm that uses biochemical signals to transfer information from one nano device to another over a short distance. The biochemical nature of the information transfer process implies that for molecular communication purposes, the development of molecular channel models should take into consideration diffusion phenomenon as well as the physical/biochemical kinetic possibilities of the process. The physical and biochemical kinetics arise at the interfaces between the diffusion channel and the transmitter/receiver units. These interfaces are herein termed molecular antennas. In this paper, we present the deterministic propagation model of the molecular communication between an immobilized nanotransmitter and nanoreceiver, where the emission and reception kinetics are taken into consideration. Specifically, we derived closed-form system-theoretic models and expressions for configurations that represent different communication systems based on the type of molecular antennas used. The antennas considered are the nanopores at the transmitter and the surface receptor proteins/enzymes at the receiver. The developed models are simulated to show the influence of parameters such as the receiver radius, surface receptor protein/enzyme concentration, and various reaction rate constants. Results show that the effective receiver surface area and the rate constants are important to the system's output performance. Assuming high rate of catalysis, the analysis of the frequency behavior of the developed propagation channels in the form of transfer functions shows significant difference introduce by the inclusion of the molecular antennas into the diffusion-only model. It is also shown that for t > > 0 and with the information molecules' concentration greater than the Michaelis-Menten kinetic constant of the systems, the inclusion of surface receptors proteins and enzymes in the models makes the system act like a band-stop filter over an infinite frequency range.

Bayesian random local clocks, or one rate to rule them all

PubMed Central

2010-01-01

Background Relaxed molecular clock models allow divergence time dating and "relaxed phylogenetic" inference, in which a time tree is estimated in the face of unequal rates across lineages. We present a new method for relaxing the assumption of a strict molecular clock using Markov chain Monte Carlo to implement Bayesian modeling averaging over random local molecular clocks. The new method approaches the problem of rate variation among lineages by proposing a series of local molecular clocks, each extending over a subregion of the full phylogeny. Each branch in a phylogeny (subtending a clade) is a possible location for a change of rate from one local clock to a new one. Thus, including both the global molecular clock and the unconstrained model results, there are a total of 22n-2 possible rate models available for averaging with 1, 2, ..., 2n - 2 different rate categories. Results We propose an efficient method to sample this model space while simultaneously estimating the phylogeny. The new method conveniently allows a direct test of the strict molecular clock, in which one rate rules them all, against a large array of alternative local molecular clock models. We illustrate the method's utility on three example data sets involving mammal, primate and influenza evolution. Finally, we explore methods to visualize the complex posterior distribution that results from inference under such models. Conclusions The examples suggest that large sequence datasets may only require a small number of local molecular clocks to reconcile their branch lengths with a time scale. All of the analyses described here are implemented in the open access software package BEAST 1.5.4 (http://beast-mcmc.googlecode.com/). PMID:20807414

Molecular dynamics computer simulation of permeation in solids

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

Pohl, P.I.; Heffelfinger, G.S.; Fisler, D.K.

1997-12-31

In this work the authors simulate permeation of gases and cations in solid models using molecular mechanics and a dual control volume grand canonical molecular dynamics technique. The molecular sieving nature of microporous zeolites are discussed and compared with that for amorphous silica made by sol-gel methods. One mesoporous and one microporous membrane model are tested with Lennard-Jones gases corresponding to He, H{sub 2}, Ar and CH{sub 4}. The mesoporous membrane model clearly follows a Knudsen diffusion mechanism, while the microporous model having a hard-sphere cutoff pore diameter of {approximately}3.4 {angstrom} demonstrates molecular sieving of the methane ({sigma} = 3.8more » {angstrom}) but anomalous behavior for Ar ({sigma} = 3.4 {angstrom}). Preliminary results of Ca{sup +} diffusion in calcite and He/H{sub 2} diffusion in polyisobutylene are also presented.« less

A statistic-thermodynamic model for the DOM degradation in the estuary

NASA Astrophysics Data System (ADS)

Zheng, Quanan; Chen, Qin; Zhao, Haihong; Shi, Jiuxin; Cao, Yong; Wang, Dan

2008-03-01

This study aims to clarify the role of dissolved salts playing in the degradation process of terrestrial dissolved organic matter (DOM) at a scale of molecular movement. The molecular thermal movement is perpetual motion. In a multi-molecular system, this random motion also causes collision between the molecules. Seawater is a multi-molecular system consisting from water, salt, and terrestrial DOM molecules. This study attributes the DOM degradation in the estuary to the inelastic collision of DOM molecule with charged salt ions. From statistic-thermodynamic theories of molecular collision, the DOM degradation model and the DOM distribution model are derived. The models are validated by the field observations and satellite data. Thus, we conclude that the inelastic collision between the terrestrial DOM molecules and dissolved salt ions in seawater is a decisive dynamic mechanism for rapid loss of terrestrial DOM.

Quantitative structure-retention relationships for gas chromatographic retention indices of alkylbenzenes with molecular graph descriptors.

PubMed

Ivanciuc, O; Ivanciuc, T; Klein, D J; Seitz, W A; Balaban, A T

2001-02-01

Quantitative structure-retention relationships (QSRR) represent statistical models that quantify the connection between the molecular structure and the chromatographic retention indices of organic compounds, allowing the prediction of retention indices of novel, not yet synthesized compounds, solely from their structural descriptors. Using multiple linear regression, QSRR models for the gas chromatographic Kováts retention indices of 129 alkylbenzenes are generated using molecular graph descriptors. The correlational ability of structural descriptors computed from 10 molecular matrices is investigated, showing that the novel reciprocal matrices give numerical indices with improved correlational ability. A QSRR equation with 5 graph descriptors gives the best calibration and prediction results, demonstrating the usefulness of the molecular graph descriptors in modeling chromatographic retention parameters. The sequential orthogonalization of descriptors suggests simpler QSRR models by eliminating redundant structural information.

Molecular Modeling on the PC (by Matthew F. Schlecht)

NASA Astrophysics Data System (ADS)

Rioux, Reviewed Frank

2000-06-01

"Computeraided molecular modeling doesn't exist for its own sake, but to contribute to scientific endeavor, and enable the scientist to work smarter." This is the last sentence of Schlecht's preface and it says something very important about contemporary scientific research in the academic and industrial venues. Owing to the accelerating improvement in computer technology (hardware and software) and its widespread availability, molecular modeling has become a reliable and important tool in chemical research. Consequently, experimentalists have incorporated molecular modeling techniques in their research, and partnerships with computational chemists have become common. This is a wellorganized and thorough monograph that devotes its attention to one type of molecular modeling, molecular mechanics, and one molecular modeling software package, PCMODEL. Schlecht targets two reader-user groups, the novice and the journeyman modeler, and articulates three goals. He wants to provide the novice with an introduction to molecular mechanics, and after that with some practical examples of the use of empirical force field calculations. His third goal is to provide the journeyman modeler with a reference work that will aid "further study and practice". These are potentially conflicting goals, but Schlecht is, in my opinion, successful because of the way his book is organized. A comprehensive treatment such as this one is not meant to be read from cover to cover, because it is both an exposition of basic principles and a user's manual. Therefore, the novice and the experienced modeler will undoubtedly use this book in different ways. For example, a novice modeler might be advised to read the Preface and Chapter 1, which together provide a broad introduction to the historical development and goals of molecular mechanics. From there the novice could go to Chapter 5 and read section 5.1 on the components of the molecular mechanics force field, which is presented in 22 pages with plenty of graphical support. The reader is now ready to move to Chapter 6 on applications and work through the 32 exercises (Chapters 3 and 4 have an additional 11 exercises) designed to illustrate the current uses of molecular modeling in academic and industrial research. Chapter 3 (Input and Output), Chapter 4 (File Formats), and the balance of Chapter 5 can be consulted as needed. For example, Chapter 5 contains 160 pages on the evolution of the various empirical force fields in use today and important information in each case on parameterization and implementation. Besides finding a clearly written, wellorganized, thorough presentation, the reader will appreciate a number of other important features. There are numerous references (993) to the primary literature covering the field of molecular mechanics from its beginnings to mid1997, when the book went to press. There is a complete glossary of PCMODEL commands, and a comprehensive and valuable glossary (77 pages) of frequently used computer terms. There are 392 figures (many of them screen captures) providing illustrations of the PCMODEL interface in use and examples of input and output files. To aid the reader/user in obtaining expertise as a modeler, a diskette containing all the structure files for all the exercises accompanies the text. In addition, the author provides, on the same diskette, a browserreadable HTML file that contains links to a large number of pertinent resources on the World Wide Web. In summary, Molecular Modeling on the PC, by Matthew Schlecht, is a very impressive contribution to the molecular modeling literature. Schlecht's book should be in every college and university library and in the personal libraries of those who want to learn more about molecular mechanics or who anticipate its use in their teaching or research.

Molecular modeling and SPRi investigations of interleukin 6 (IL6) protein and DNA aptamers.

PubMed

Rhinehardt, Kristen L; Vance, Stephen A; Mohan, Ram V; Sandros, Marinella; Srinivas, Goundla

2018-06-01

Interleukin 6 (IL6), an inflammatory response protein has major implications in immune-related inflammatory diseases. Identification of aptamers for the IL6 protein aids in diagnostic, therapeutic, and theranostic applications. Three different DNA aptamers and their interactions with IL6 protein were extensively investigated in a phosphate buffed saline (PBS) solution. Molecular-level modeling through molecular dynamics provided insights of structural, conformational changes and specific binding domains of these protein-aptamer complexes. Multiple simulations reveal consistent binding region for all protein-aptamer complexes. Conformational changes coupled with quantitative analysis of center of mass (COM) distance, radius of gyration (R g ), and number of intermolecular hydrogen bonds in each IL6 protein-aptamer complex was used to determine their binding performance strength and obtain molecular configurations with strong binding. A similarity comparison of the molecular configurations with strong binding from molecular-level modeling concurred with Surface Plasmon Resonance imaging (SPRi) for these three aptamer complexes, thus corroborating molecular modeling analysis findings. Insights from the natural progression of IL6 protein-aptamer binding modeled in this work has identified key features such as the orientation and location of the aptamer in the binding event. These key features are not readily feasible from wet lab experiments and impact the efficacy of the aptamers in diagnostic and theranostic applications.

Modeling the Hydrogen Bond within Molecular Dynamics

ERIC Educational Resources Information Center

Lykos, Peter

2004-01-01

The structure of a hydrogen bond is elucidated within the framework of molecular dynamics based on the model of Rahman and Stillinger (R-S) liquid water treatment. Thus, undergraduates are exposed to the powerful but simple use of classical mechanics to solid objects from a molecular viewpoint.

Multifunctional receptor model for dioxin and related compound toxic action: possible thyroid hormone-responsive effector-linked site.

PubMed Central

McKinney, J D

1989-01-01

Molecular/theoretical modeling studies have revealed that thyroid hormones and toxic chlorinated aromatic hydrocarbons of environmental significance (for which dioxin or TCDD is the prototype) have similar structural properties that could be important in molecular recognition in biochemical systems. These molecular properties include a somewhat rigid, sterically accessible and polarizable aromatic ring and size-limited, hydrophobic lateral substituents, usually contained in opposite adjoining rings of a diphenyl compound. These molecular properties define the primary binding groups thought to be important in molecular recognition of both types of structures in biochemical systems. Similar molecular reactivities are supported by the demonstration of effective specific binding of thyroid hormones and chlorinated aromatic hydrocarbons with four different proteins, enzymes, or receptor preparations that are known or suspected to be involved in the expression of thyroid hormone activity. These binding interactions represent both aromatic-aromatic (stacking) and molecular cleft-type recognition processes. A multiple protein or multifunctional receptor-ligand binding mechanism model is proposed as a way of visualizing the details and possible role of both the stacking and cleft type molecular recognition factors in the expression of biological activity. The model suggests a means by which hormone-responsive effector-linked sites (possible protein-protein-DNA complexes) can maintain highly structurally specific control of hormone action. Finally, the model also provides a theoretical basis for the design and conduct of further biological experimentation on the molecular mechanism(s) of action of toxic chlorinated aromatic hydrocarbons and thyroid hormones. Images FIGURE 3. A FIGURE 3. B FIGURE 3. C FIGURE 3. D PMID:2551666

An Easily Constructed and Versatile Molecular Model

NASA Astrophysics Data System (ADS)

Hernandez, Sandra A.; Rodriguez, Nora M.; Quinzani, Oscar

1996-08-01

Three-dimensional molecular models are powerful tools used in basic courses of general and organic chemistry when the students must visualize the spatial distributions of atoms in molecules and relate them to the physical and chemical properties of such molecules. This article discusses inexpensive, easily carried, and semipermanent molecular models that the students may build by themselves. These models are based upon two different types of arrays of thin flexible wires, like telephone hook-up wires, which may be bent easily but keep their shapes.

Open source molecular modeling.

PubMed

Pirhadi, Somayeh; Sunseri, Jocelyn; Koes, David Ryan

2016-09-01

The success of molecular modeling and computational chemistry efforts are, by definition, dependent on quality software applications. Open source software development provides many advantages to users of modeling applications, not the least of which is that the software is free and completely extendable. In this review we categorize, enumerate, and describe available open source software packages for molecular modeling and computational chemistry. An updated online version of this catalog can be found at https://opensourcemolecularmodeling.github.io. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

Validation of systems biology derived molecular markers of renal donor organ status associated with long term allograft function.

PubMed

Perco, Paul; Heinzel, Andreas; Leierer, Johannes; Schneeberger, Stefan; Bösmüller, Claudia; Oberhuber, Rupert; Wagner, Silvia; Engler, Franziska; Mayer, Gert

2018-05-03

Donor organ quality affects long term outcome after renal transplantation. A variety of prognostic molecular markers is available, yet their validity often remains undetermined. A network-based molecular model reflecting donor kidney status based on transcriptomics data and molecular features reported in scientific literature to be associated with chronic allograft nephropathy was created. Significantly enriched biological processes were identified and representative markers were selected. An independent kidney pre-implantation transcriptomics dataset of 76 organs was used to predict estimated glomerular filtration rate (eGFR) values twelve months after transplantation using available clinical data and marker expression values. The best-performing regression model solely based on the clinical parameters donor age, donor gender, and recipient gender explained 17% of variance in post-transplant eGFR values. The five molecular markers EGF, CD2BP2, RALBP1, SF3B1, and DDX19B representing key molecular processes of the constructed renal donor organ status molecular model in addition to the clinical parameters significantly improved model performance (p-value = 0.0007) explaining around 33% of the variability of eGFR values twelve months after transplantation. Collectively, molecular markers reflecting donor organ status significantly add to prediction of post-transplant renal function when added to the clinical parameters donor age and gender.

Teaching 1H NMR Spectrometry Using Computer Modeling.

ERIC Educational Resources Information Center

Habata, Yoichi; Akabori, Sadatoshi

2001-01-01

Molecular modeling by computer is used to display stereochemistry, molecular orbitals, structure of transition states, and progress of reactions. Describes new ideas for teaching 1H NMR spectroscopy using computer modeling. (Contains 12 references.) (ASK)

Molecular Modeling and Computational Chemistry at Humboldt State University.

ERIC Educational Resources Information Center

Paselk, Richard A.; Zoellner, Robert W.

2002-01-01

Describes a molecular modeling and computational chemistry (MM&CC) facility for undergraduate instruction and research at Humboldt State University. This facility complex allows the introduction of MM&CC throughout the chemistry curriculum with tailored experiments in general, organic, and inorganic courses as well as a new molecular modeling…

Molecular dynamics simulations of biological membranes and membrane proteins using enhanced conformational sampling algorithms.

PubMed

Mori, Takaharu; Miyashita, Naoyuki; Im, Wonpil; Feig, Michael; Sugita, Yuji

2016-07-01

This paper reviews various enhanced conformational sampling methods and explicit/implicit solvent/membrane models, as well as their recent applications to the exploration of the structure and dynamics of membranes and membrane proteins. Molecular dynamics simulations have become an essential tool to investigate biological problems, and their success relies on proper molecular models together with efficient conformational sampling methods. The implicit representation of solvent/membrane environments is reasonable approximation to the explicit all-atom models, considering the balance between computational cost and simulation accuracy. Implicit models can be easily combined with replica-exchange molecular dynamics methods to explore a wider conformational space of a protein. Other molecular models and enhanced conformational sampling methods are also briefly discussed. As application examples, we introduce recent simulation studies of glycophorin A, phospholamban, amyloid precursor protein, and mixed lipid bilayers and discuss the accuracy and efficiency of each simulation model and method. This article is part of a Special Issue entitled: Membrane Proteins edited by J.C. Gumbart and Sergei Noskov. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

A pharmacophore model specific to active site of CYP1A2 with a novel molecular modeling explorer and CoMFA.

PubMed

Zhang, Tao; Wei, Dong-Qing; Chou, Kuo-Chen

2012-03-01

Comparative molecular field analysis (CoMFA) is a widely used 3D-QSAR method by which we can investigate the potential relation between biological activity of compounds and their structural features. In this study, a new application of this approach is presented by combining the molecular modeling with a new developed pharmacophore model specific to CYP1A2 active site. During constructing the model, we used the molecular dynamics simulation and molecular docking method to select the sensible binding conformations for 17 CYP1A2 substrates based on the experimental data. Subsequently, the results obtained via the alignment of binding conformations of substrates were projected onto the active- site residues, upon which a simple blueprint of active site was produced. It was validated by the experimental and computational results that the model did exhibit the high degree of rationality and provide useful insights into the substrate binding. It is anticipated that our approach can be extended to investigate the protein-ligand interactions for many other enzyme-catalyzed systems as well.

Supercomputer applications in molecular modeling.

PubMed

Gund, T M

1988-01-01

An overview of the functions performed by molecular modeling is given. Molecular modeling techniques benefiting from supercomputing are described, namely, conformation, search, deriving bioactive conformations, pharmacophoric pattern searching, receptor mapping, and electrostatic properties. The use of supercomputers for problems that are computationally intensive, such as protein structure prediction, protein dynamics and reactivity, protein conformations, and energetics of binding is also examined. The current status of supercomputing and supercomputer resources are discussed.

Physical models have gender-specific effects on student understanding of protein structure-function relationships.

PubMed

Forbes-Lorman, Robin M; Harris, Michelle A; Chang, Wesley S; Dent, Erik W; Nordheim, Erik V; Franzen, Margaret A

2016-07-08

Understanding how basic structural units influence function is identified as a foundational/core concept for undergraduate biological and biochemical literacy. It is essential for students to understand this concept at all size scales, but it is often more difficult for students to understand structure-function relationships at the molecular level, which they cannot as effectively visualize. Students need to develop accurate, 3-dimensional mental models of biomolecules to understand how biomolecular structure affects cellular functions at the molecular level, yet most traditional curricular tools such as textbooks include only 2-dimensional representations. We used a controlled, backward design approach to investigate how hand-held physical molecular model use affected students' ability to logically predict structure-function relationships. Brief (one class period) physical model use increased quiz score for females, whereas there was no significant increase in score for males using physical models. Females also self-reported higher learning gains in their understanding of context-specific protein function. Gender differences in spatial visualization may explain the gender-specific benefits of physical model use observed. © 2016 The Authors Biochemistry and Molecular Biology Education published by Wiley Periodicals, Inc. on behalf of International Union of Biochemistry and Molecular Biology, 44(4):326-335, 2016. © 2016 The International Union of Biochemistry and Molecular Biology.

Modeling stochastic kinetics of molecular machines at multiple levels: from molecules to modules.

PubMed

Chowdhury, Debashish

2013-06-04

A molecular machine is either a single macromolecule or a macromolecular complex. In spite of the striking superficial similarities between these natural nanomachines and their man-made macroscopic counterparts, there are crucial differences. Molecular machines in a living cell operate stochastically in an isothermal environment far from thermodynamic equilibrium. In this mini-review we present a catalog of the molecular machines and an inventory of the essential toolbox for theoretically modeling these machines. The tool kits include 1), nonequilibrium statistical-physics techniques for modeling machines and machine-driven processes; and 2), statistical-inference methods for reverse engineering a functional machine from the empirical data. The cell is often likened to a microfactory in which the machineries are organized in modular fashion; each module consists of strongly coupled multiple machines, but different modules interact weakly with each other. This microfactory has its own automated supply chain and delivery system. Buoyed by the success achieved in modeling individual molecular machines, we advocate integration of these models in the near future to develop models of functional modules. A system-level description of the cell from the perspective of molecular machinery (the mechanome) is likely to emerge from further integrations that we envisage here. Copyright © 2013 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Structural Analysis Of CD59 Of Chinese Tree Shrew: A New Reference Molecule For Human Immune System Specific CD59 Drug Discovery.

PubMed

Panda, Subhamay; Kumari, Leena; Panda, Santamay

2017-11-17

Chinese tree shrews (Tupaia belangeri chinensis) bear several characteristics that are considered to be very crucial for utilizing in animal experimental models in biomedical research. Subsequent to the identification of key aspects and signaling pathways in nervous and immune systems, it is revealed that tree shrews acquires shared common as well as unique characteristics, and hence offers a genetic basis for employing this animal as a prospective model for biomedical research. CD59 glycoprotein, commonly referred to as MAC-inhibitory protein (MAC-IP), membrane inhibitor of reactive lysis (MIRL), or protectin, is encoded by the CD59 gene in human beings. It is the member of the LY6/uPAR/alpha-neurotoxin protein family. With this initial point the objective of this study was to determine a comparative composite based structure of CD59 of Chinese tree shrew. The additional objective of this study was to examine the distribution of negatively and positively charged amino acid over molecular modeled structure, distribution of secondary structural elements, hydrophobicity molecular surface analysis and electrostatic potential analysis with the assistance of several bioinformatical analytical tools. CD59 Amino acid sequence of Chinese tree shrew collected from the online database system of National Centre for Biotechnology Information. SignalP 4.0 online server was employed for detection of signal peptide instance within the protein sequence of CD59. Molecular model structure of CD59 protein was generated by the Iterative Threading ASSEmbly Refinement (I-TASSER) suite. The confirmation for three-dimensional structural model was evaluated by structure validation tools. Location of negatively and positively charged amino acid over molecular modeled structure, distribution of secondary structural elements, and hydrophobicity molecular surface analysis was performed with the help of Chimera tool. Electrostatic potential analysis was carried out with the adaptive Poisson-Boltzmann solver package. Subsequently validated model was used for the functionally critical amino acids and active site prediction. The functionally critical amino acids and ligand- binding site (LBS) of the proteins (modeled) was determined using the COACH program. Analysis of Ramachandran plot for Chinese tree shrew depicted that overall, 100% of the residues in homology model were observed in allowed and favored regions, sequentially leading to the validation of the standard of generated protein structural model. In case of CD59 of Chinese tree shrew, the total score of G-factor was found to be -0.66 that was generally larger than the acceptable value. This approach suggests the significance and acceptability of the modeled structure of CD59 of Chinese tree shrew. The molecular model data in cooperation to other relevant post model analysis data put forward molecular insight to protecting activity of CD59 protein molecule of Chinese tree shrew. In the present study, we have proposed the first molecular model structure of uncharted CD59 of Chinese tree shrew by significantly utilizing the comparative composite modeling approach. Therefore, the development of a structural model of the CD59 protein was carried out and analyzed further for deducing molecular enrichment technique. The collaborative effort of molecular model and other relevant data of post model analysis carry forward molecular understanding to protecting activity of CD59 functions towards better insight of features of this natural lead compound. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Modeling of molecular diffusion and thermal conduction with multi-particle interaction in compressible turbulence

NASA Astrophysics Data System (ADS)

Tai, Y.; Watanabe, T.; Nagata, K.

2018-03-01

A mixing volume model (MVM) originally proposed for molecular diffusion in incompressible flows is extended as a model for molecular diffusion and thermal conduction in compressible turbulence. The model, established for implementation in Lagrangian simulations, is based on the interactions among spatially distributed notional particles within a finite volume. The MVM is tested with the direct numerical simulation of compressible planar jets with the jet Mach number ranging from 0.6 to 2.6. The MVM well predicts molecular diffusion and thermal conduction for a wide range of the size of mixing volume and the number of mixing particles. In the transitional region of the jet, where the scalar field exhibits a sharp jump at the edge of the shear layer, a smaller mixing volume is required for an accurate prediction of mean effects of molecular diffusion. The mixing time scale in the model is defined as the time scale of diffusive effects at a length scale of the mixing volume. The mixing time scale is well correlated for passive scalar and temperature. Probability density functions of the mixing time scale are similar for molecular diffusion and thermal conduction when the mixing volume is larger than a dissipative scale because the mixing time scale at small scales is easily affected by different distributions of intermittent small-scale structures between passive scalar and temperature. The MVM with an assumption of equal mixing time scales for molecular diffusion and thermal conduction is useful in the modeling of the thermal conduction when the modeling of the dissipation rate of temperature fluctuations is difficult.

The application of molecular modelling in the safety assessment of chemicals: A case study on ligand-dependent PPARγ dysregulation.

PubMed

Al Sharif, Merilin; Tsakovska, Ivanka; Pajeva, Ilza; Alov, Petko; Fioravanzo, Elena; Bassan, Arianna; Kovarich, Simona; Yang, Chihae; Mostrag-Szlichtyng, Aleksandra; Vitcheva, Vessela; Worth, Andrew P; Richarz, Andrea-N; Cronin, Mark T D

2017-12-01

The aim of this paper was to provide a proof of concept demonstrating that molecular modelling methodologies can be employed as a part of an integrated strategy to support toxicity prediction consistent with the mode of action/adverse outcome pathway (MoA/AOP) framework. To illustrate the role of molecular modelling in predictive toxicology, a case study was undertaken in which molecular modelling methodologies were employed to predict the activation of the peroxisome proliferator-activated nuclear receptor γ (PPARγ) as a potential molecular initiating event (MIE) for liver steatosis. A stepwise procedure combining different in silico approaches (virtual screening based on docking and pharmacophore filtering, and molecular field analysis) was developed to screen for PPARγ full agonists and to predict their transactivation activity (EC 50 ). The performance metrics of the classification model to predict PPARγ full agonists were balanced accuracy=81%, sensitivity=85% and specificity=76%. The 3D QSAR model developed to predict EC 50 of PPARγ full agonists had the following statistical parameters: q 2 cv =0.610, N opt =7, SEP cv =0.505, r 2 pr =0.552. To support the linkage of PPARγ agonism predictions to prosteatotic potential, molecular modelling was combined with independently performed mechanistic mining of available in vivo toxicity data followed by ToxPrint chemotypes analysis. The approaches investigated demonstrated a potential to predict the MIE, to facilitate the process of MoA/AOP elaboration, to increase the scientific confidence in AOP, and to become a basis for 3D chemotype development. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

A log-normal distribution model for the molecular weight of aquatic fulvic acids

USGS Publications Warehouse

Cabaniss, S.E.; Zhou, Q.; Maurice, P.A.; Chin, Y.-P.; Aiken, G.R.

2000-01-01

The molecular weight of humic substances influences their proton and metal binding, organic pollutant partitioning, adsorption onto minerals and activated carbon, and behavior during water treatment. We propose a lognormal model for the molecular weight distribution in aquatic fulvic acids to provide a conceptual framework for studying these size effects. The normal curve mean and standard deviation are readily calculated from measured M(n) and M(w) and vary from 2.7 to 3 for the means and from 0.28 to 0.37 for the standard deviations for typical aquatic fulvic acids. The model is consistent with several types of molecular weight data, including the shapes of high- pressure size-exclusion chromatography (HP-SEC) peaks. Applications of the model to electrostatic interactions, pollutant solubilization, and adsorption are explored in illustrative calculations.The molecular weight of humic substances influences their proton and metal binding, organic pollutant partitioning, adsorption onto minerals and activated carbon, and behavior during water treatment. We propose a log-normal model for the molecular weight distribution in aquatic fulvic acids to provide a conceptual framework for studying these size effects. The normal curve mean and standard deviation are readily calculated from measured Mn and Mw and vary from 2.7 to 3 for the means and from 0.28 to 0.37 for the standard deviations for typical aquatic fulvic acids. The model is consistent with several type's of molecular weight data, including the shapes of high-pressure size-exclusion chromatography (HP-SEC) peaks. Applications of the model to electrostatic interactions, pollutant solubilization, and adsorption are explored in illustrative calculations.

Interaction of a sodium ion with the water liquid-vapor interface

NASA Technical Reports Server (NTRS)

Wilson, M. A.; Pohorille, A.; Pratt, L. R.; MacElroy, R. D. (Principal Investigator)

1989-01-01

Molecular dynamics results are presented for the density profile of a sodium ion near the water liquid-vapor interface at 320 K. These results are compared with the predictions of a simple dielectric model for the interaction of a monovalent ion with this interface. The interfacial region described by the model profile is too narrow and the profile decreases too abruptly near the solution interface. Thus, the simple model does not provide a satisfactory description of the molecular dynamics results for ion positions within two molecular diameters from the solution interface where appreciable ion concentrations are observed. These results suggest that surfaces associated with dielectric models of ionic processes at aqueous solution interfaces should be located at least two molecular diameters inside the liquid phase. A free energy expense of about 2 kcal/mol is required to move the ion within two molecular layers of the free water liquid-vapor interface.

In vitro molecular machine learning algorithm via symmetric internal loops of DNA.

PubMed

Lee, Ji-Hoon; Lee, Seung Hwan; Baek, Christina; Chun, Hyosun; Ryu, Je-Hwan; Kim, Jin-Woo; Deaton, Russell; Zhang, Byoung-Tak

2017-08-01

Programmable biomolecules, such as DNA strands, deoxyribozymes, and restriction enzymes, have been used to solve computational problems, construct large-scale logic circuits, and program simple molecular games. Although studies have shown the potential of molecular computing, the capability of computational learning with DNA molecules, i.e., molecular machine learning, has yet to be experimentally verified. Here, we present a novel molecular learning in vitro model in which symmetric internal loops of double-stranded DNA are exploited to measure the differences between training instances, thus enabling the molecules to learn from small errors. The model was evaluated on a data set of twenty dialogue sentences obtained from the television shows Friends and Prison Break. The wet DNA-computing experiments confirmed that the molecular learning machine was able to generalize the dialogue patterns of each show and successfully identify the show from which the sentences originated. The molecular machine learning model described here opens the way for solving machine learning problems in computer science and biology using in vitro molecular computing with the data encoded in DNA molecules. Copyright © 2017. Published by Elsevier B.V.

Investigations of FAK inhibitors: a combination of 3D-QSAR, docking, and molecular dynamics simulations studies.

PubMed

Cheng, Peng; Li, Jiaojiao; Wang, Juan; Zhang, Xiaoyun; Zhai, Honglin

2018-05-01

Focal adhesion kinase (FAK) is one kind of tyrosine kinases that modulates integrin and growth factor signaling pathways, which is a promising therapeutic target because of involving in cancer cell migration, proliferation, and survival. To investigate the mechanism between FAK and triazinic inhibitors and design high activity inhibitors, a molecular modeling integrated with 3D-QSAR, molecular docking, molecular dynamics simulations, and binding free energy calculations was performed. The optimum CoMFA and CoMSIA models showed good reliability and satisfactory predictability (with Q 2  = 0.663, R 2  = 0.987, [Formula: see text] = 0.921 and Q 2  = 0.670, R 2  = 0.981, [Formula: see text] = 0.953). Its contour maps could provide structural features to improve inhibitory activity. Furthermore, a good consistency between contour maps, docking, and molecular dynamics simulations strongly demonstrates that the molecular modeling is reliable. Based on it, we designed several new compounds and their inhibitory activities were validated by the molecular models. We expect our studies could bring new ideas to promote the development of novel inhibitors with higher inhibitory activity for FAK.

Practical quantum mechanics-based fragment methods for predicting molecular crystal properties.

PubMed

Wen, Shuhao; Nanda, Kaushik; Huang, Yuanhang; Beran, Gregory J O

2012-06-07

Significant advances in fragment-based electronic structure methods have created a real alternative to force-field and density functional techniques in condensed-phase problems such as molecular crystals. This perspective article highlights some of the important challenges in modeling molecular crystals and discusses techniques for addressing them. First, we survey recent developments in fragment-based methods for molecular crystals. Second, we use examples from our own recent research on a fragment-based QM/MM method, the hybrid many-body interaction (HMBI) model, to analyze the physical requirements for a practical and effective molecular crystal model chemistry. We demonstrate that it is possible to predict molecular crystal lattice energies to within a couple kJ mol(-1) and lattice parameters to within a few percent in small-molecule crystals. Fragment methods provide a systematically improvable approach to making predictions in the condensed phase, which is critical to making robust predictions regarding the subtle energy differences found in molecular crystals.

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

Barbante, Paolo; Frezzotti, Aldo; Gibelli, Livio

The unsteady evaporation of a thin planar liquid film is studied by molecular dynamics simulations of Lennard-Jones fluid. The obtained results are compared with the predictions of a diffuse interface model in which capillary Korteweg contributions are added to hydrodynamic equations, in order to obtain a unified description of the liquid bulk, liquid-vapor interface and vapor region. Particular care has been taken in constructing a diffuse interface model matching the thermodynamic and transport properties of the Lennard-Jones fluid. The comparison of diffuse interface model and molecular dynamics results shows that, although good agreement is obtained in equilibrium conditions, remarkable deviationsmore » of diffuse interface model predictions from the reference molecular dynamics results are observed in the simulation of liquid film evaporation. It is also observed that molecular dynamics results are in good agreement with preliminary results obtained from a composite model which describes the liquid film by a standard hydrodynamic model and the vapor by the Boltzmann equation. The two mathematical model models are connected by kinetic boundary conditions assuming unit evaporation coefficient.« less

Insights from molecular modeling and dynamics simulation of pathogen resistance (R) protein from brinjal.

PubMed

Shrivastava, Dipty; Nain, Vikrant; Sahi, Shakti; Verma, Anju; Sharma, Priyanka; Sharma, Prakash Chand; Kumar, Polumetla Ananda

2011-01-22

Resistance (R) protein recognizes molecular signature of pathogen infection and activates downstream hypersensitive response signalling in plants. R protein works as a molecular switch for pathogen defence signalling and represent one of the largest plant gene family. Hence, understanding molecular structure and function of R proteins has been of paramount importance for plant biologists. The present study is aimed at predicting structure of R proteins signalling domains (CC-NBS) by creating a homology model, refining and optimising the model by molecular dynamics simulation and comparing ADP and ATP binding. Based on sequence similarity with proteins of known structures, CC-NBS domains were initially modelled using CED- 4 (cell death abnormality protein) and APAF-1 (apoptotic protease activating factor) as multiple templates. The final CC-NBS structural model was built and optimized by molecular dynamic simulation for 5 nanoseconds (ns). Docking of ADP and ATP at active site shows that both ligand bind specifically with same residues and with minor difference (1 Kcal/mol) in binding energy. Sharing of binding site by ADP and ATP and low difference in their binding site makes CC-NBS suitable for working as molecular switch. Furthermore, structural superimposition elucidate that CC-NBS and CARD (caspase recruitment domains) domain of CED-4 have low RMSD value of 0.9 A° Availability of 3D structural model for both CC and NBS domains will . help in getting deeper insight in these pathogen defence genes.

MIDG-Emerging grid technologies for multi-site preclinical molecular imaging research communities.

PubMed

Lee, Jasper; Documet, Jorge; Liu, Brent; Park, Ryan; Tank, Archana; Huang, H K

2011-03-01

Molecular imaging is the visualization and identification of specific molecules in anatomy for insight into metabolic pathways, tissue consistency, and tracing of solute transport mechanisms. This paper presents the Molecular Imaging Data Grid (MIDG) which utilizes emerging grid technologies in preclinical molecular imaging to facilitate data sharing and discovery between preclinical molecular imaging facilities and their collaborating investigator institutions to expedite translational sciences research. Grid-enabled archiving, management, and distribution of animal-model imaging datasets help preclinical investigators to monitor, access and share their imaging data remotely, and promote preclinical imaging facilities to share published imaging datasets as resources for new investigators. The system architecture of the Molecular Imaging Data Grid is described in a four layer diagram. A data model for preclinical molecular imaging datasets is also presented based on imaging modalities currently used in a molecular imaging center. The MIDG system components and connectivity are presented. And finally, the workflow steps for grid-based archiving, management, and retrieval of preclincial molecular imaging data are described. Initial performance tests of the Molecular Imaging Data Grid system have been conducted at the USC IPILab using dedicated VMware servers. System connectivity, evaluated datasets, and preliminary results are presented. The results show the system's feasibility, limitations, direction of future research. Translational and interdisciplinary research in medicine is increasingly interested in cellular and molecular biology activity at the preclinical levels, utilizing molecular imaging methods on animal models. The task of integrated archiving, management, and distribution of these preclinical molecular imaging datasets at preclinical molecular imaging facilities is challenging due to disparate imaging systems and multiple off-site investigators. A Molecular Imaging Data Grid design, implementation, and initial evaluation is presented to demonstrate the secure and novel data grid solution for sharing preclinical molecular imaging data across the wide-area-network (WAN).

Designing an educative curriculum unit for teaching molecular geometry in high school chemistry

NASA Astrophysics Data System (ADS)

Makarious, Nader N.

Chemistry is a highly abstract discipline that is taught and learned with the aid of various models. Among the most challenging, yet a fundamental topic in general chemistry at the high school level, is molecular geometry. This study focused on developing exemplary educative curriculum materials pertaining to the topic of molecular geometry. The methodology used in this study consisted of several steps. First, a diverse set of models were analyzed to determine to what extent each model serves its purpose in teaching molecular geometry. Second, a number of high school teachers and college chemistry professors were asked to share their experiences on using models in teaching molecular geometry through an online questionnaire. Third, findings from the comparative analysis of models, teachers’ experiences, literature review on models and students’ misconceptions, the curriculum expectations of the Next Generation Science Standards and their emphasis on three-dimensional learning and nature of science (NOS) contributed to the development of the molecular geometry unit. Fourth, the developed unit was reviewed by fellow teachers and doctoral-level science education experts and was revised to further improve its coherence and clarity in support of teaching and learning of the molecular geometry concepts. The produced educative curriculum materials focus on the scientific practice of developing and using models as promoted in the Next Generations Science Standards (NGSS) while also addressing nature of science (NOS) goals. The educative features of the newly developed unit support teachers’ pedagogical knowledge (PK) and pedagogical content knowledge (PCK). The unit includes an overview, teacher’s guide, and eight detailed lesson plans with inquiry oriented modeling activities replete with models and suggestions for teachers, as well as formative and summative assessment tasks. The unit design process serves as a model for redesigning other instructional units in science disciplines in general and chemistry courses in particular.

Molecular Modeling on Berberine Derivatives toward BuChE: An Integrated Study with Quantitative Structure-Activity Relationships Models, Molecular Docking, and Molecular Dynamics Simulations.

PubMed

Fang, Jiansong; Pang, Xiaocong; Wu, Ping; Yan, Rong; Gao, Li; Li, Chao; Lian, Wenwen; Wang, Qi; Liu, Ai-lin; Du, Guan-hua

2016-05-01

A dataset of 67 berberine derivatives for the inhibition of butyrylcholinesterase (BuChE) was studied based on the combination of quantitative structure-activity relationships models, molecular docking, and molecular dynamics methods. First, a series of berberine derivatives were reported, and their inhibitory activities toward butyrylcholinesterase (BuChE) were evaluated. By 2D- quantitative structure-activity relationships studies, the best model built by partial least-square had a conventional correlation coefficient of the training set (R(2)) of 0.883, a cross-validation correlation coefficient (Qcv2) of 0.777, and a conventional correlation coefficient of the test set (Rpred2) of 0.775. The model was also confirmed by Y-randomization examination. In addition, the molecular docking and molecular dynamics simulation were performed to better elucidate the inhibitory mechanism of three typical berberine derivatives (berberine, C2, and C55) toward BuChE. The predicted binding free energy results were consistent with the experimental data and showed that the van der Waals energy term (ΔEvdw) difference played the most important role in differentiating the activity among the three inhibitors (berberine, C2, and C55). The developed quantitative structure-activity relationships models provide details on the fine relationship linking structure and activity and offer clues for structural modifications, and the molecular simulation helps to understand the inhibitory mechanism of the three typical inhibitors. In conclusion, the results of this study provide useful clues for new drug design and discovery of BuChE inhibitors from berberine derivatives. © 2015 John Wiley & Sons A/S.

Flexoelectricity of model and living membranes.

PubMed

Petrov, Alexander G

2002-03-19

The theory and experiments on model and biomembrane flexoelectricity are reviewed. Biological implications of flexoelectricity are underlined. Molecular machinery and molecular electronics applications are pointed out.

Molecular Modeling as a Self-Taught Component of a Conventional Undergraduate Chemical Reaction Engineering Course

ERIC Educational Resources Information Center

Rothe, Erhard W.; Zygmunt, William E.

2016-01-01

We inserted a self-taught molecular modeling project into an otherwise conventional undergraduate chemical-reaction-engineering course. Our objectives were that students should (a) learn with minimal instructor intervention, (b) gain an appreciation for the relationship between molecular structure and, first, macroscopic state functions in…

Molecular Modeling of Estrogen Receptor Using Molecular Operating Environment

ERIC Educational Resources Information Center

Roy, Urmi; Luck, Linda A.

2007-01-01

Molecular modeling is pervasive in the pharmaceutical industry that employs many of our students from Biology, Chemistry and the interdisciplinary majors. To expose our students to this important aspect of their education we have incorporated a set of tutorials in our Biochemistry class. The present article describes one of our tutorials where…

Numerical study of influence of molecular diffusion in the Mild combustion regime

NASA Astrophysics Data System (ADS)

Mardani, Amir; Tabejamaat, Sadegh; Ghamari, Mohsen

2010-09-01

In this paper, the importance of molecular diffusion versus turbulent transport in the moderate or intense low-oxygen dilution (Mild) combustion mode has been numerically studied. The experimental conditions of Dally et al. [Proc. Combust. Inst. 29 (2002) 1147-1154] were used for modelling. The EDC model was used to describe the turbulence-chemistry interaction. The DRM-22 reduced mechanism and the GRI 2.11 full mechanism were used to represent the chemical reactions of an H2/methane jet flame. The importance of molecular diffusion for various O2 levels, jet Reynolds numbers and H2 fuel contents was investigated. Results show that the molecular diffusion in Mild combustion cannot be ignored in comparison with the turbulent transport. Also, the method of inclusion of molecular diffusion in combustion modelling has a considerable effect on the accuracy of numerical modelling of Mild combustion. By decreasing the jet Reynolds number, decreasing the oxygen concentration in the airflow or increasing H2 in the fuel mixture, the influence of molecular diffusion on Mild combustion increases.

Studies of chain substitution caused sub-fibril level differences in stiffness and ultrastructure of wildtype and oim/oim collagen fibers using multifrequency-AFM and molecular modeling.

PubMed

Li, Tao; Chang, Shu-Wei; Rodriguez-Florez, Naiara; Buehler, Markus J; Shefelbine, Sandra; Dao, Ming; Zeng, Kaiyang

2016-11-01

Molecular alteration in type I collagen, i.e., substituting the α2 chain with α1 chain in tropocollagen molecule, can cause osteogenesis imperfecta (OI), a brittle bone disease, which can be represented by a mouse model (oim/oim). In this work, we use dual-frequency Atomic Force Microscopy (AFM) and incorporated with molecular modeling to quantify the ultrastructure and stiffness of the individual native collagen fibers from wildtype (+/+) and oim/oim diseased mice humeri. Our work presents direct experimental evidences that the +/+ fibers have highly organized and compact ultrastructure and corresponding ordered stiffness distribution. In contrast, oim/oim fibers have ordered but loosely packed ultrastructure with uncorrelated stiffness distribution, as well as local defects. The molecular model also demonstrates the structural and molecular packing differences between +/+ and oim/oim collagens. The molecular mutation significantly altered sub-fibril structure and mechanical property of collagen fibers. This study can give the new insight for the mechanisms and treatment of the brittle bone disease. Copyright © 2016 Elsevier Ltd. All rights reserved.

Molecular Modeling Studies of 4,5-Dihydro-1H-pyrazolo[4,3-h] quinazoline Derivatives as Potent CDK2/Cyclin A Inhibitors Using 3D-QSAR and Docking

PubMed Central

Ai, Yong; Wang, Shao-Teng; Sun, Ping-Hua; Song, Fa-Jun

2010-01-01

CDK2/cyclin A has appeared as an attractive drug targets over the years with diverse therapeutic potentials. A computational strategy based on comparative molecular fields analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) followed by molecular docking studies were performed on a series of 4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline derivatives as potent CDK2/cyclin A inhibitors. The CoMFA and CoMSIA models, using 38 molecules in the training set, gave r2cv values of 0.747 and 0.518 and r2 values of 0.970 and 0.934, respectively. 3D contour maps generated by the CoMFA and CoMSIA models were used to identify the key structural requirements responsible for the biological activity. Molecular docking was applied to explore the binding mode between the ligands and the receptor. The information obtained from molecular modeling studies may be helpful to design novel inhibitors of CDK2/cyclin A with desired activity. PMID:21152296

Molecular modeling studies of 4,5-dihydro-1H-pyrazolo[4,3-h] quinazoline derivatives as potent CDK2/Cyclin a inhibitors using 3D-QSAR and docking.

PubMed

Ai, Yong; Wang, Shao-Teng; Sun, Ping-Hua; Song, Fa-Jun

2010-09-28

CDK2/cyclin A has appeared as an attractive drug targets over the years with diverse therapeutic potentials. A computational strategy based on comparative molecular fields analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) followed by molecular docking studies were performed on a series of 4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline derivatives as potent CDK2/cyclin A inhibitors. The CoMFA and CoMSIA models, using 38 molecules in the training set, gave r(2) (cv) values of 0.747 and 0.518 and r(2) values of 0.970 and 0.934, respectively. 3D contour maps generated by the CoMFA and CoMSIA models were used to identify the key structural requirements responsible for the biological activity. Molecular docking was applied to explore the binding mode between the ligands and the receptor. The information obtained from molecular modeling studies may be helpful to design novel inhibitors of CDK2/cyclin A with desired activity.

Fine- and hyperfine-structure effects in molecular photoionization. II. Resonance-enhanced multiphoton ionization and hyperfine-selective generation of molecular cations

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

Germann, Matthias; Willitsch, Stefan, E-mail: stefan.willitsch@unibas.ch

2016-07-28

Resonance-enhanced multiphoton ionization (REMPI) is a widely used technique for studying molecular photoionization and producing molecular cations for spectroscopy and dynamics studies. Here, we present a model for describing hyperfine-structure effects in the REMPI process and for predicting hyperfine populations in molecular ions produced by this method. This model is a generalization of our model for fine- and hyperfine-structure effects in one-photon ionization of molecules presented in Paper I [M. Germann and S. Willitsch, J. Chem. Phys. 145, 044314 (2016)]. This generalization is achieved by covering two main aspects: (1) treatment of the neutral bound-bound transition including the hyperfine structuremore » that makes up the first step of the REMPI process and (2) modification of our ionization model to account for anisotropic populations resulting from this first excitation step. Our findings may be used for analyzing results from experiments with molecular ions produced by REMPI and may serve as a theoretical background for hyperfine-selective ionization experiments.« less

Many Molecular Properties from One Kernel in Chemical Space

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

Ramakrishnan, Raghunathan; von Lilienfeld, O. Anatole

We introduce property-independent kernels for machine learning modeling of arbitrarily many molecular properties. The kernels encode molecular structures for training sets of varying size, as well as similarity measures sufficiently diffuse in chemical space to sample over all training molecules. Corresponding molecular reference properties provided, they enable the instantaneous generation of ML models which can systematically be improved through the addition of more data. This idea is exemplified for single kernel based modeling of internal energy, enthalpy, free energy, heat capacity, polarizability, electronic spread, zero-point vibrational energy, energies of frontier orbitals, HOMOLUMO gap, and the highest fundamental vibrational wavenumber. Modelsmore » of these properties are trained and tested using 112 kilo organic molecules of similar size. Resulting models are discussed as well as the kernels’ use for generating and using other property models.« less

Improving a Lecture-Size Molecular Model Set by Repurposing Used Whiteboard Markers

ERIC Educational Resources Information Center

Dragojlovic, Veljko

2015-01-01

Preparation of an inexpensive model set from whiteboard markers and either HGS molecular model set or atoms made of wood is described. The model set is relatively easy to prepare and is sufficiently large to be suitable as an instructor set for use in lectures.

Building better water models using the shape of the charge distribution of a water molecule

NASA Astrophysics Data System (ADS)

Dharmawardhana, Chamila Chathuranga; Ichiye, Toshiko

2017-11-01

The unique properties of liquid water apparently arise from more than just the tetrahedral bond angle between the nuclei of a water molecule since simple three-site models of water are poor at mimicking these properties in computer simulations. Four- and five-site models add partial charges on dummy sites and are better at modeling these properties, which suggests that the shape of charge distribution is important. Since a multipole expansion of the electrostatic potential describes a charge distribution in an orthogonal basis set that is exact in the limit of infinite order, multipoles may be an even better way to model the charge distribution. In particular, molecular multipoles up to the octupole centered on the oxygen appear to describe the electrostatic potential from electronic structure calculations better than four- and five-site models, and molecular multipole models give better agreement with the temperature and pressure dependence of many liquid state properties of water while retaining the computational efficiency of three-site models. Here, the influence of the shape of the molecular charge distribution on liquid state properties is examined by correlating multipoles of non-polarizable water models with their liquid state properties in computer simulations. This will aid in the development of accurate water models for classical simulations as well as in determining the accuracy needed in quantum mechanical/molecular mechanical studies and ab initio molecular dynamics simulations of water. More fundamentally, this will lead to a greater understanding of how the charge distribution of a water molecule leads to the unique properties of liquid water. In particular, these studies indicate that p-orbital charge out of the molecular plane is important.

Complex molecular assemblies at hand via interactive simulations.

PubMed

Delalande, Olivier; Férey, Nicolas; Grasseau, Gilles; Baaden, Marc

2009-11-30

Studying complex molecular assemblies interactively is becoming an increasingly appealing approach to molecular modeling. Here we focus on interactive molecular dynamics (IMD) as a textbook example for interactive simulation methods. Such simulations can be useful in exploring and generating hypotheses about the structural and mechanical aspects of biomolecular interactions. For the first time, we carry out low-resolution coarse-grain IMD simulations. Such simplified modeling methods currently appear to be more suitable for interactive experiments and represent a well-balanced compromise between an important gain in computational speed versus a moderate loss in modeling accuracy compared to higher resolution all-atom simulations. This is particularly useful for initial exploration and hypothesis development for rare molecular interaction events. We evaluate which applications are currently feasible using molecular assemblies from 1900 to over 300,000 particles. Three biochemical systems are discussed: the guanylate kinase (GK) enzyme, the outer membrane protease T and the soluble N-ethylmaleimide-sensitive factor attachment protein receptors complex involved in membrane fusion. We induce large conformational changes, carry out interactive docking experiments, probe lipid-protein interactions and are able to sense the mechanical properties of a molecular model. Furthermore, such interactive simulations facilitate exploration of modeling parameters for method improvement. For the purpose of these simulations, we have developed a freely available software library called MDDriver. It uses the IMD protocol from NAMD and facilitates the implementation and application of interactive simulations. With MDDriver it becomes very easy to render any particle-based molecular simulation engine interactive. Here we use its implementation in the Gromacs software as an example. Copyright 2009 Wiley Periodicals, Inc.

2D- and 3D-quantitative structure-activity relationship studies for a series of phenazine N,N'-dioxide as antitumour agents.

PubMed

Cunha, Jonathan Da; Lavaggi, María Laura; Abasolo, María Inés; Cerecetto, Hugo; González, Mercedes

2011-12-01

Hypoxic regions of tumours are associated with increased resistance to radiation and chemotherapy. Nevertheless, hypoxia has been used as a tool for specific activation of some antitumour prodrugs, named bioreductive agents. Phenazine dioxides are an example of such bioreductive prodrugs. Our 2D-quantitative structure activity relationship studies established that phenazine dioxides electronic and lipophilic descriptors are related to survival fraction in oxia or in hypoxia. Additionally, statistically significant models, derived by partial least squares, were obtained between survival fraction in oxia and comparative molecular field analysis standard model (r² = 0.755, q² = 0.505 and F = 26.70) or comparative molecular similarity indices analysis-combined steric and electrostatic fields (r² = 0.757, q² = 0.527 and F = 14.93), and survival fraction in hypoxia and comparative molecular field analysis standard model (r² = 0.736, q² = 0.521 and F = 18.63) or comparative molecular similarity indices analysis-hydrogen bond acceptor field (r² = 0.858, q² = 0.737 and F = 27.19). Categorical classification was used for the biological parameter selective cytotoxicity emerging also good models, derived by soft independent modelling of class analogy, with both comparative molecular field analysis standard model (96% of overall classification accuracy) and comparative molecular similarity indices analysis-steric field (92% of overall classification accuracy). 2D- and 3D-quantitative structure-activity relationships models provided important insights into the chemical and structural basis involved in the molecular recognition process of these phenazines as bioreductive agents and should be useful for the design of new structurally related analogues with improved potency. © 2011 John Wiley & Sons A/S.

Macro and micro analysis of small molecule diffusion in amorphous polymers

NASA Astrophysics Data System (ADS)

Putta, Santosh Krishna

In this study, both macroscopic and microscopic numerical techniques have been explored, to model and understand the diffusion behavior of small molecules in amorphous polymers, which very often do not follow the classical Fickian law. It was attempted to understand the influence of various aspects of the molecular structure of a polymer on its macroscopic diffusion behavior. At the macroscopic level, a hybrid finite-element/finite-difference model is developed to implement the coupled diffusion and deformation constitutive equations. A viscoelasticity theory, combined with time-freevolume superposition is used to model the deformation processes. A freevolume-based model is used to model the diffusion processes. The freevolume in the polymer is used as a coupling factor between the deformation and the diffusion processes. The model is shown to qualitatively describe some of the typical non-Fickian diffusion behavior in polymers. However, it does not directly involve the microstructure of a polymer. Further, some of the input parameters to the model are difficult to obtain experimentally. A numerical microscopic approach is therefore adopted to study the molecular structure of polymers. A molecular mechanics and dynamics technique combined with a modified Rotational Isomeric State (RIS) approach, is followed to generate the molecular structure for two types of polycarbonates, and, two types of polyacrylates, starting only with their chemical structures. A new efficient 3-D algorithm for Delaunay Tessellation is developed, and, then applied to discretize the molecular structure into Delaunay Tetrahedra. By using the dicretized molecular structure, size, shape, and, connectivity of free-spaces for small molecule diffusion in the above mentioned polymers, are then studied in relation to their diffusion properties. The influence of polymer and side chain flexibility, and diffusant-diffusant and diffusant-polymer molecular interactions, is also discussed with respect to the diffusion properties.

Molecular Model of a Quantum Dot Beyond the Constant Interaction Approximation

NASA Astrophysics Data System (ADS)

Temirov, Ruslan; Green, Matthew F. B.; Friedrich, Niklas; Leinen, Philipp; Esat, Taner; Chmielniak, Pawel; Sarwar, Sidra; Rawson, Jeff; Kögerler, Paul; Wagner, Christian; Rohlfing, Michael; Tautz, F. Stefan

2018-05-01

We present a physically intuitive model of molecular quantum dots beyond the constant interaction approximation. It accurately describes their charging behavior and allows the extraction of important molecular properties that are otherwise experimentally inaccessible. The model is applied to data recorded with a noncontact atomic force microscope on three different molecules that act as a quantum dot when attached to the microscope tip. The results are in excellent agreement with first-principles simulations.

3D-quantitative structure-activity relationship studies on benzothiadiazepine hydroxamates as inhibitors of tumor necrosis factor-alpha converting enzyme.

PubMed

Murumkar, Prashant R; Giridhar, Rajani; Yadav, Mange Ram

2008-04-01

A set of 29 benzothiadiazepine hydroxamates having selective tumor necrosis factor-alpha converting enzyme inhibitory activity were used to compare the quality and predictive power of 3D-quantitative structure-activity relationship, comparative molecular field analysis, and comparative molecular similarity indices models for the atom-based, centroid/atom-based, data-based, and docked conformer-based alignment. Removal of two outliers from the initial training set of molecules improved the predictivity of models. Among the 3D-quantitative structure-activity relationship models developed using the above four alignments, the database alignment provided the optimal predictive comparative molecular field analysis model for the training set with cross-validated r(2) (q(2)) = 0.510, non-cross-validated r(2) = 0.972, standard error of estimates (s) = 0.098, and F = 215.44 and the optimal comparative molecular similarity indices model with cross-validated r(2) (q(2)) = 0.556, non-cross-validated r(2) = 0.946, standard error of estimates (s) = 0.163, and F = 99.785. These models also showed the best test set prediction for six compounds with predictive r(2) values of 0.460 and 0.535, respectively. The contour maps obtained from 3D-quantitative structure-activity relationship studies were appraised for activity trends for the molecules analyzed. The comparative molecular similarity indices models exhibited good external predictivity as compared with that of comparative molecular field analysis models. The data generated from the present study helped us to further design and report some novel and potent tumor necrosis factor-alpha converting enzyme inhibitors.

An Introductory Classroom Exercise on Protein Molecular Model Visualization and Detailed Analysis of Protein-Ligand Binding

ERIC Educational Resources Information Center

Poeylaut-Palena, Andres, A.; de los Angeles Laborde, Maria

2013-01-01

A learning module for molecular level analysis of protein structure and ligand/drug interaction through the visualization of X-ray diffraction is presented. Using DeepView as molecular model visualization software, students learn about the general concepts of protein structure. This Biochemistry classroom exercise is designed to be carried out by…

The Use of Molecular Modeling as "Pseudoexperimental" Data for Teaching VSEPR as a Hands-On General Chemistry Activity

ERIC Educational Resources Information Center

Martin, Christopher B.; Vandehoef, Crissie; Cook, Allison

2015-01-01

A hands-on activity appropriate for first-semester general chemistry students is presented that combines traditional VSEPR methods of predicting molecular geometries with introductory use of molecular modeling. Students analyze a series of previously calculated output files consisting of several molecules each in various geometries. Each structure…

Prediction of quantum interference in molecular junctions using a parabolic diagram: Understanding the origin of Fano and anti- resonances

NASA Astrophysics Data System (ADS)

Nozaki, Daijiro; Avdoshenko, Stanislav M.; Sevinçli, Hâldun; Gutierrez, Rafael; Cuniberti, Gianaurelio

2013-03-01

Recently the interest in quantum interference (QI) phenomena in molecular devices (molecular junctions) has been growing due to the unique features observed in the transmission spectra. In order to design single molecular devices exploiting QI effects as desired, it is necessary to provide simple rules for predicting the appearance of QI effects such as anti-resonances or Fano line shapes and for controlling them. In this study, we derive a transmission function of a generic molecular junction with a side group (T-shaped molecular junction) using a minimal toy model. We developed a simple method to predict the appearance of quantum interference, Fano resonances or anti- resonances, and its position in the conductance spectrum by introducing a simple graphical representation (parabolic model). Using it we can easily visualize the relation between the key electronic parameters and the positions of normal resonant peaks and anti-resonant peaks induced by quantum interference in the conductance spectrum. We also demonstrate Fano and anti-resonance in T-shaped molecular junctions using a simple tight-binding model. This parabolic model enables one to infer on-site energies of T-shaped molecules and the coupling between side group and main conduction channel from transmission spectra.

DeePMD-kit: A deep learning package for many-body potential energy representation and molecular dynamics

NASA Astrophysics Data System (ADS)

Wang, Han; Zhang, Linfeng; Han, Jiequn; E, Weinan

2018-07-01

Recent developments in many-body potential energy representation via deep learning have brought new hopes to addressing the accuracy-versus-efficiency dilemma in molecular simulations. Here we describe DeePMD-kit, a package written in Python/C++ that has been designed to minimize the effort required to build deep learning based representation of potential energy and force field and to perform molecular dynamics. Potential applications of DeePMD-kit span from finite molecules to extended systems and from metallic systems to chemically bonded systems. DeePMD-kit is interfaced with TensorFlow, one of the most popular deep learning frameworks, making the training process highly automatic and efficient. On the other end, DeePMD-kit is interfaced with high-performance classical molecular dynamics and quantum (path-integral) molecular dynamics packages, i.e., LAMMPS and the i-PI, respectively. Thus, upon training, the potential energy and force field models can be used to perform efficient molecular simulations for different purposes. As an example of the many potential applications of the package, we use DeePMD-kit to learn the interatomic potential energy and forces of a water model using data obtained from density functional theory. We demonstrate that the resulted molecular dynamics model reproduces accurately the structural information contained in the original model.

Extending rule-based methods to model molecular geometry and 3D model resolution.

PubMed

Hoard, Brittany; Jacobson, Bruna; Manavi, Kasra; Tapia, Lydia

2016-08-01

Computational modeling is an important tool for the study of complex biochemical processes associated with cell signaling networks. However, it is challenging to simulate processes that involve hundreds of large molecules due to the high computational cost of such simulations. Rule-based modeling is a method that can be used to simulate these processes with reasonably low computational cost, but traditional rule-based modeling approaches do not include details of molecular geometry. The incorporation of geometry into biochemical models can more accurately capture details of these processes, and may lead to insights into how geometry affects the products that form. Furthermore, geometric rule-based modeling can be used to complement other computational methods that explicitly represent molecular geometry in order to quantify binding site accessibility and steric effects. We propose a novel implementation of rule-based modeling that encodes details of molecular geometry into the rules and binding rates. We demonstrate how rules are constructed according to the molecular curvature. We then perform a study of antigen-antibody aggregation using our proposed method. We simulate the binding of antibody complexes to binding regions of the shrimp allergen Pen a 1 using a previously developed 3D rigid-body Monte Carlo simulation, and we analyze the aggregate sizes. Then, using our novel approach, we optimize a rule-based model according to the geometry of the Pen a 1 molecule and the data from the Monte Carlo simulation. We use the distances between the binding regions of Pen a 1 to optimize the rules and binding rates. We perform this procedure for multiple conformations of Pen a 1 and analyze the impact of conformation and resolution on the optimal rule-based model. We find that the optimized rule-based models provide information about the average steric hindrance between binding regions and the probability that antibodies will bind to these regions. These optimized models quantify the variation in aggregate size that results from differences in molecular geometry and from model resolution.

Testing the molecular clock using mechanistic models of fossil preservation and molecular evolution

PubMed Central

2017-01-01

Molecular sequence data provide information about relative times only, and fossil-based age constraints are the ultimate source of information about absolute times in molecular clock dating analyses. Thus, fossil calibrations are critical to molecular clock dating, but competing methods are difficult to evaluate empirically because the true evolutionary time scale is never known. Here, we combine mechanistic models of fossil preservation and sequence evolution in simulations to evaluate different approaches to constructing fossil calibrations and their impact on Bayesian molecular clock dating, and the relative impact of fossil versus molecular sampling. We show that divergence time estimation is impacted by the model of fossil preservation, sampling intensity and tree shape. The addition of sequence data may improve molecular clock estimates, but accuracy and precision is dominated by the quality of the fossil calibrations. Posterior means and medians are poor representatives of true divergence times; posterior intervals provide a much more accurate estimate of divergence times, though they may be wide and often do not have high coverage probability. Our results highlight the importance of increased fossil sampling and improved statistical approaches to generating calibrations, which should incorporate the non-uniform nature of ecological and temporal fossil species distributions. PMID:28637852

A simple model for molecular hydrogen chemistry coupled to radiation hydrodynamics

NASA Astrophysics Data System (ADS)

Nickerson, Sarah; Teyssier, Romain; Rosdahl, Joakim

2018-06-01

We introduce non-equilibrium molecular hydrogen chemistry into the radiation-hydrodynamics code RAMSES-RT. This is an adaptive mesh refinement grid code with radiation hydrodynamics that couples the thermal chemistry of hydrogen and helium to moment-based radiative transfer with the Eddington tensor closure model. The H2 physics that we include are formation on dust grains, gas phase formation, formation by three-body collisions, collisional destruction, photodissociation, photoionisation, cosmic ray ionisation and self-shielding. In particular, we implement the first model for H2 self-shielding that is tied locally to moment-based radiative transfer by enhancing photo-destruction. This self-shielding from Lyman-Werner line overlap is critical to H2 formation and gas cooling. We can now track the non-equilibrium evolution of molecular, atomic, and ionised hydrogen species with their corresponding dissociating and ionising photon groups. Over a series of tests we show that our model works well compared to specialised photodissociation region codes. We successfully reproduce the transition depth between molecular and atomic hydrogen, molecular cooling of the gas, and a realistic Strömgren sphere embedded in a molecular medium. In this paper we focus on test cases to demonstrate the validity of our model on small scales. Our ultimate goal is to implement this in large-scale galactic simulations.

Monogenic Mouse Models of Autism Spectrum Disorders: Common Mechanisms and Missing Links

PubMed Central

Hulbert, Samuel W.; Jiang, Yong-hui

2016-01-01

Autism Spectrum Disorders (ASDs) present unique challenges in the fields of genetics and neurobiology because of the clinical and molecular heterogeneity underlying these disorders. Genetic mutations found in ASD patients provide opportunities to dissect the molecular and circuit mechanisms underlying autistic behaviors using animal models. Ongoing studies of genetically modified models have offered critical insight into possible common mechanisms arising from different mutations, but links between molecular abnormalities and behavioral phenotypes remain elusive. The challenges encountered in modeling autism in mice demand a new analytic paradigm that integrates behavioral analysis with circuit-level analysis in genetically modified models with strong construct validity. PMID:26733386

Understanding valence-shell electron-pair repulsion (VSEPR) theory using origami molecular models

NASA Astrophysics Data System (ADS)

Endah Saraswati, Teguh; Saputro, Sulistyo; Ramli, Murni; Praseptiangga, Danar; Khasanah, Nurul; Marwati, Sri

2017-01-01

Valence-shell electron-pair repulsion (VSEPR) theory is conventionally used to predict molecular geometry. However, it is difficult to explore the full implications of this theory by simply drawing chemical structures. Here, we introduce origami modelling as a more accessible approach for exploration of the VSEPR theory. Our technique is simple, readily accessible and inexpensive compared with other sophisticated methods such as computer simulation or commercial three-dimensional modelling kits. This method can be implemented in chemistry education at both the high school and university levels. We discuss the example of a simple molecular structure prediction for ammonia (NH3). Using the origami model, both molecular shape and the scientific justification can be visualized easily. This ‘hands-on’ approach to building molecules will help promote understanding of VSEPR theory.

Limiting assumptions in molecular modeling: electrostatics.

PubMed

Marshall, Garland R

2013-02-01

Molecular mechanics attempts to represent intermolecular interactions in terms of classical physics. Initial efforts assumed a point charge located at the atom center and coulombic interactions. It is been recognized over multiple decades that simply representing electrostatics with a charge on each atom failed to reproduce the electrostatic potential surrounding a molecule as estimated by quantum mechanics. Molecular orbitals are not spherically symmetrical, an implicit assumption of monopole electrostatics. This perspective reviews recent evidence that requires use of multipole electrostatics and polarizability in molecular modeling.

Electron Transport Modeling of Molecular Nanoscale Bridges Used in Energy Conversion Schemes

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

Dunietz, Barry D

2016-08-09

The goal of the research program is to reliably describe electron transport and transfer processes at the molecular level. Such insight is essential for improving molecular applications of solar and thermal energy conversion. We develop electronic structure models to study (1) photoinduced electron transfer and transport processes in organic semiconducting materials, and (2) charge and heat transport through molecular bridges. We seek fundamental understanding of key processes, which lead to design new experiments and ultimately to achieve systems with improved properties.

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.

Multipole correction of atomic monopole models of molecular charge distribution. I. Peptides

NASA Technical Reports Server (NTRS)

Sokalski, W. A.; Keller, D. A.; Ornstein, R. L.; Rein, R.

1993-01-01

The defects in atomic monopole models of molecular charge distribution have been analyzed for several model-blocked peptides and compared with accurate quantum chemical values. The results indicate that the angular characteristics of the molecular electrostatic potential around functional groups capable of forming hydrogen bonds can be considerably distorted within various models relying upon isotropic atomic charges only. It is shown that these defects can be corrected by augmenting the atomic point charge models by cumulative atomic multipole moments (CAMMs). Alternatively, sets of off-center atomic point charges could be automatically derived from respective multipoles, providing approximately equivalent corrections. For the first time, correlated atomic multipoles have been calculated for N-acetyl, N'-methylamide-blocked derivatives of glycine, alanine, cysteine, threonine, leucine, lysine, and serine using the MP2 method. The role of the correlation effects in the peptide molecular charge distribution are discussed.

Two-Dimensional Model of Scrolled Packings of Molecular Nanoribbons

NASA Astrophysics Data System (ADS)

Savin, A. V.; Mazo, M. A.

2018-04-01

A simplified model of the in-plane molecular chain, allowing the description of folded and scrolled packings of molecular nanoribbons of different structures, is proposed. Using this model, possible steady states of single-layer nanoribbons scrolls of graphene, graphane, fluorographene, and fluorographane (graphene hydrogenated on the one side and fluorinated on the other side) are obtained. Their stability is demonstrated and their energy is calculated as a function of the nanoribbon length. It is shown that the scrolled packing is the most energetically favorable nanoribbon conformation at long lengths. The existences of scrolled packings for fluorographene nanoribbons and the existence of two different scroll types corresponding to left- and right-hand Archimedean spirals for fluorographane nanoribbons in the chain model are shown for the first time. The simplicity of the proposed model makes it possible to consider the dynamics of scrolls of rather long molecular nanoribbons at long enough time intervals.

Atomistic insight into the catalytic mechanism of glycosyltransferases by combined quantum mechanics/molecular mechanics (QM/MM) methods.

PubMed

Tvaroška, Igor

2015-02-11

Glycosyltransferases catalyze the formation of glycosidic bonds by assisting the transfer of a sugar residue from donors to specific acceptor molecules. Although structural and kinetic data have provided insight into mechanistic strategies employed by these enzymes, molecular modeling studies are essential for the understanding of glycosyltransferase catalyzed reactions at the atomistic level. For such modeling, combined quantum mechanics/molecular mechanics (QM/MM) methods have emerged as crucial. These methods allow the modeling of enzymatic reactions by using quantum mechanical methods for the calculation of the electronic structure of the active site models and treating the remaining enzyme environment by faster molecular mechanics methods. Herein, the application of QM/MM methods to glycosyltransferase catalyzed reactions is reviewed, and the insight from modeling of glycosyl transfer into the mechanisms and transition states structures of both inverting and retaining glycosyltransferases are discussed. Copyright © 2014 Elsevier Ltd. All rights reserved.

COLLABORATIVE RESEARCH AND DEVELOPMENT (CR&D) Delivery Order 0059: Molecular Dynamics Modeling Support

DTIC Science & Technology

2008-03-01

Molecular Dynamics Simulations 5 Theory: Equilibrium Molecular Dynamics Simulations 6 Theory: Non...Equilibrium Molecular Dynamics Simulations 8 Carbon Nanotube Simulations : Approach and results from equilibrium and non-equilibrium molecular dynamics ...touched from the perspective of molecular dynamics simulations . However, ordered systems such as “Carbon Nanotubes” have been investigated in terms

Uncovering molecular processes in crystal nucleation and growth by using molecular simulation.

PubMed

Anwar, Jamshed; Zahn, Dirk

2011-02-25

Exploring nucleation processes by molecular simulation provides a mechanistic understanding at the atomic level and also enables kinetic and thermodynamic quantities to be estimated. However, whilst the potential for modeling crystal nucleation and growth processes is immense, there are specific technical challenges to modeling. In general, rare events, such as nucleation cannot be simulated using a direct "brute force" molecular dynamics approach. The limited time and length scales that are accessible by conventional molecular dynamics simulations have inspired a number of advances to tackle problems that were considered outside the scope of molecular simulation. While general insights and features could be explored from efficient generic models, new methods paved the way to realistic crystal nucleation scenarios. The association of single ions in solvent environments, the mechanisms of motif formation, ripening reactions, and the self-organization of nanocrystals can now be investigated at the molecular level. The analysis of interactions with growth-controlling additives gives a new understanding of functionalized nanocrystals and the precipitation of composite materials. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Magnetic polyoxometalates: from molecular magnetism to molecular spintronics and quantum computing.

PubMed

Clemente-Juan, Juan M; Coronado, Eugenio; Gaita-Ariño, Alejandro

2012-11-21

In this review we discuss the relevance of polyoxometalate (POM) chemistry to provide model objects in molecular magnetism. We present several potential applications in nanomagnetism, in particular, in molecular spintronics and quantum computing.

Smart Sensing Based on DNA-Metal Interaction Enables a Label-Free and Resettable Security Model of Electrochemical Molecular Keypad Lock.

PubMed

Du, Yan; Han, Xu; Wang, Chenxu; Li, Yunhui; Li, Bingling; Duan, Hongwei

2018-01-26

Recently, molecular keypad locks have received increasing attention. As a new subgroup of smart biosensors, they show great potential for protecting information as a molecular security data processor, rather than merely molecular recognition and quantitation. Herein, label-free electrochemically transduced Ag + and cysteine (Cys) sensors were developed. A molecular keypad lock model with reset function was successfully realized based on the balanced interaction of metal ion with its nucleic acid and chemical ligands. The correct input of "1-2-3" (i.e., "Ag + -Cys-cDNA") is the only password of such molecular keypad lock. Moreover, the resetting process of either correct or wrong input order could be easily made by Cys, buffer, and DI water treatment. Therefore, our system provides an even smarter system of molecular keypad lock, which could inhibit illegal access of unauthorized users, holding great promise in information protection at the molecular level.

Gas solubility in dilute solutions: A novel molecular thermodynamic perspective

NASA Astrophysics Data System (ADS)

Chialvo, Ariel A.

2018-05-01

We present an explicit molecular-based interpretation of the thermodynamic phase equilibrium underlying gas solubility in liquids, through rigorous links between the microstructure of the dilute systems and the relevant macroscopic quantities that characterize their solution thermodynamics. We apply the formal analysis to unravel and highlight the molecular-level nature of the approximations behind the widely used Krichevsky-Kasarnovsky [J. Am. Chem. Soc. 57, 2168 (1935)] and Krichevsky-Ilinskaya [Acta Physicochim. 20, 327 (1945)] equations for the modeling of gas solubility. Then, we implement a general molecular-based approach to gas solubility and illustrate it by studying Lennard-Jones binary systems whose microstructure and thermodynamic properties were consistently generated via integral equation calculations. Furthermore, guided by the molecular-based analysis, we propose a novel macroscopic modeling approach to gas solubility, emphasize some usually overlook modeling subtleties, and identify novel interdependences among relevant solubility quantities that can be used as either handy modeling constraints or tools for consistency tests.

MAIN software for density averaging, model building, structure refinement and validation

PubMed Central

Turk, Dušan

2013-01-01

MAIN is software that has been designed to interactively perform the complex tasks of macromolecular crystal structure determination and validation. Using MAIN, it is possible to perform density modification, manual and semi-automated or automated model building and rebuilding, real- and reciprocal-space structure optimization and refinement, map calculations and various types of molecular structure validation. The prompt availability of various analytical tools and the immediate visualization of molecular and map objects allow a user to efficiently progress towards the completed refined structure. The extraordinary depth perception of molecular objects in three dimensions that is provided by MAIN is achieved by the clarity and contrast of colours and the smooth rotation of the displayed objects. MAIN allows simultaneous work on several molecular models and various crystal forms. The strength of MAIN lies in its manipulation of averaged density maps and molecular models when noncrystallographic symmetry (NCS) is present. Using MAIN, it is possible to optimize NCS parameters and envelopes and to refine the structure in single or multiple crystal forms. PMID:23897458

Multi-level molecular modelling for plasma medicine

NASA Astrophysics Data System (ADS)

Bogaerts, Annemie; Khosravian, Narjes; Van der Paal, Jonas; Verlackt, Christof C. W.; Yusupov, Maksudbek; Kamaraj, Balu; Neyts, Erik C.

2016-02-01

Modelling at the molecular or atomic scale can be very useful for obtaining a better insight in plasma medicine. This paper gives an overview of different atomic/molecular scale modelling approaches that can be used to study the direct interaction of plasma species with biomolecules or the consequences of these interactions for the biomolecules on a somewhat longer time-scale. These approaches include density functional theory (DFT), density functional based tight binding (DFTB), classical reactive and non-reactive molecular dynamics (MD) and united-atom or coarse-grained MD, as well as hybrid quantum mechanics/molecular mechanics (QM/MM) methods. Specific examples will be given for three important types of biomolecules, present in human cells, i.e. proteins, DNA and phospholipids found in the cell membrane. The results show that each of these modelling approaches has its specific strengths and limitations, and is particularly useful for certain applications. A multi-level approach is therefore most suitable for obtaining a global picture of the plasma-biomolecule interactions.

Gas solubility in dilute solutions: A novel molecular thermodynamic perspective.

PubMed

Chialvo, Ariel A

2018-05-07

We present an explicit molecular-based interpretation of the thermodynamic phase equilibrium underlying gas solubility in liquids, through rigorous links between the microstructure of the dilute systems and the relevant macroscopic quantities that characterize their solution thermodynamics. We apply the formal analysis to unravel and highlight the molecular-level nature of the approximations behind the widely used Krichevsky-Kasarnovsky [J. Am. Chem. Soc. 57, 2168 (1935)] and Krichevsky-Ilinskaya [Acta Physicochim. 20, 327 (1945)] equations for the modeling of gas solubility. Then, we implement a general molecular-based approach to gas solubility and illustrate it by studying Lennard-Jones binary systems whose microstructure and thermodynamic properties were consistently generated via integral equation calculations. Furthermore, guided by the molecular-based analysis, we propose a novel macroscopic modeling approach to gas solubility, emphasize some usually overlook modeling subtleties, and identify novel interdependences among relevant solubility quantities that can be used as either handy modeling constraints or tools for consistency tests.

Challenges in Materials Transformation Modeling for Polyolefins Industry

NASA Astrophysics Data System (ADS)

Lai, Shih-Yaw; Swogger, Kurt W.

2004-06-01

Unlike most published polymer processing and/or forming research, the transformation of polyolefins to fabricated articles often involves non-confined flow or so-called free surface flow (e.g. fiber spinning, blown films, and cast films) in which elongational flow takes place during a fabrication process. Obviously, the characterization and validation of extensional rheological parameters and their use to develop rheological constitutive models are the focus of polyolefins materials transformation research. Unfortunately, there are challenges that remain with limited validation for non-linear, non-isothermal constitutive models for polyolefins. Further complexity arises in the transformation of polyolefins in the elongational flow system as it involves stress-induced crystallization process. The complicated nature of elongational, non-linear rheology and non-isothermal crystallization kinetics make the development of numerical methods very challenging for the polyolefins materials forming modeling. From the product based company standpoint, the challenges of materials transformation research go beyond elongational rheology, crystallization kinetics and its numerical modeling. In order to make models useful for the polyolefin industry, it is critical to develop links between molecular parameters to both equipment and materials forming parameters. The recent advances in the constrained geometry catalysis and materials sciences understanding (INSITE technology and molecular design capability) has made industrial polyolefinic materials forming modeling more viable due to the fact that the molecular structure of the polymer can be well predicted and controlled during the polymerization. In this paper, we will discuss inter-relationship (models) among molecular parameters such as polymer molecular weight (Mw), molecular weight distribution (MWD), long chain branching (LCB), short chain branching (SCB or comonomer types and distribution) and their affects on shear and elongational rheologies, on tie-molecules probabilities, on non-isothermal stress-induced crystallization, on crystalline/amorphous orientation vs. mechanical property relationship, etc. All of the above mentioned inter-relationships (models) are critical to the successful development of a knowledge based industrial model. Dow Polyolefins and Elastomers business is one of the world largest polyolefins resin producers with the most advanced INSITE technology and a "6-Day model" molecular design capability. Dow also offers one of the broadest polyolefinic product ranges and applications to the market.

The great descriptor melting pot: mixing descriptors for the common good of QSAR models.

PubMed

Tseng, Yufeng J; Hopfinger, Anton J; Esposito, Emilio Xavier

2012-01-01

The usefulness and utility of QSAR modeling depends heavily on the ability to estimate the values of molecular descriptors relevant to the endpoints of interest followed by an optimized selection of descriptors to form the best QSAR models from a representative set of the endpoints of interest. The performance of a QSAR model is directly related to its molecular descriptors. QSAR modeling, specifically model construction and optimization, has benefited from its ability to borrow from other unrelated fields, yet the molecular descriptors that form QSAR models have remained basically unchanged in both form and preferred usage. There are many types of endpoints that require multiple classes of descriptors (descriptors that encode 1D through multi-dimensional, 4D and above, content) needed to most fully capture the molecular features and interactions that contribute to the endpoint. The advantages of QSAR models constructed from multiple, and different, descriptor classes have been demonstrated in the exploration of markedly different, and principally biological systems and endpoints. Multiple examples of such QSAR applications using different descriptor sets are described and that examined. The take-home-message is that a major part of the future of QSAR analysis, and its application to modeling biological potency, ADME-Tox properties, general use in virtual screening applications, as well as its expanding use into new fields for building QSPR models, lies in developing strategies that combine and use 1D through nD molecular descriptors.

Bacterial molecular networks: bridging the gap between functional genomics and dynamical modelling.

PubMed

van Helden, Jacques; Toussaint, Ariane; Thieffry, Denis

2012-01-01

This introductory review synthesizes the contents of the volume Bacterial Molecular Networks of the series Methods in Molecular Biology. This volume gathers 9 reviews and 16 method chapters describing computational protocols for the analysis of metabolic pathways, protein interaction networks, and regulatory networks. Each protocol is documented by concrete case studies dedicated to model bacteria or interacting populations. Altogether, the chapters provide a representative overview of state-of-the-art methods for data integration and retrieval, network visualization, graph analysis, and dynamical modelling.

Mitochondrial genetics in Bakers' yeast: a molecular mechanism for recombinational polarity and suppressiveness.

PubMed

Perlman, P S; Birky, C W

1974-11-01

Recombinational polarity and suppressiveness are two well-known but puzzling cytoplasmic genetic phenomena in bakers' yeast, Saccharomyces cerevisiae. Little progress has been made in characterizing the underlying molecular mechanisms of these phenomena. In this paper we describe a molecular model for recombinational polarity that is compatible with the available genetic evidence. The model stresses the role of small deletions and excision/repair processes in otherwise canonical recombinational events. According to the model, both phenomena require recombination and may share mechanistic elements.

An engineering assessment of gas/surface interactions in free-molecular aerodynamics

NASA Technical Reports Server (NTRS)

Knox, E. C.; Liver, Peter A.; Collins, Frank G.

1991-01-01

Data available on the gas/surface interaction (GSI) phenomenon, particularly in the rarefied to near-free-molecular flow regime are collected, categorized, and analyzed with a purpose of developing a GSI model that could be used as a guide to spacecraft designers. The study shows that there are not enough useful data for building a high-confidence GSI model. However, sufficient results are obtained to suggest that continued reliance on the diffuse GSI model is inappropriate, particularly in the near-free-molecular regime.

Analysis of Physical and Numerical Factors for Prediction of UV Radiation from High Altitude Two-Phase Plumes

DTIC Science & Technology

2008-05-30

varies from continuum inside the nozzle, to transitional in the near field, to free molecular in the far field of the plume. The scales of interest vary...unity based on the rocket length. This results in the formation of a viscous shock layer characterized by a bimodal molecular velocity distribution. The...transfer model. Previous analysis21 have shown that the heat transfer model implemented in CFD++ is reproduced closely by the free molecular model

Application of DEN refinement and automated model building to a difficult case of molecular-replacement phasing: the structure of a putative succinyl-diaminopimelate desuccinylase from Corynebacterium glutamicum.

PubMed

Brunger, Axel T; Das, Debanu; Deacon, Ashley M; Grant, Joanna; Terwilliger, Thomas C; Read, Randy J; Adams, Paul D; Levitt, Michael; Schröder, Gunnar F

2012-04-01

Phasing by molecular replacement remains difficult for targets that are far from the search model or in situations where the crystal diffracts only weakly or to low resolution. Here, the process of determining and refining the structure of Cgl1109, a putative succinyl-diaminopimelate desuccinylase from Corynebacterium glutamicum, at ∼3 Å resolution is described using a combination of homology modeling with MODELLER, molecular-replacement phasing with Phaser, deformable elastic network (DEN) refinement and automated model building using AutoBuild in a semi-automated fashion, followed by final refinement cycles with phenix.refine and Coot. This difficult molecular-replacement case illustrates the power of including DEN restraints derived from a starting model to guide the movements of the model during refinement. The resulting improved model phases provide better starting points for automated model building and produce more significant difference peaks in anomalous difference Fourier maps to locate anomalous scatterers than does standard refinement. This example also illustrates a current limitation of automated procedures that require manual adjustment of local sequence misalignments between the homology model and the target sequence.

Application of DEN refinement and automated model building to a difficult case of molecular-replacement phasing: the structure of a putative succinyl-diaminopimelate desuccinylase from Corynebacterium glutamicum

PubMed Central

Brunger, Axel T.; Das, Debanu; Deacon, Ashley M.; Grant, Joanna; Terwilliger, Thomas C.; Read, Randy J.; Adams, Paul D.; Levitt, Michael; Schröder, Gunnar F.

2012-01-01

Phasing by molecular replacement remains difficult for targets that are far from the search model or in situations where the crystal diffracts only weakly or to low resolution. Here, the process of determining and refining the structure of Cgl1109, a putative succinyl-diaminopimelate desuccinylase from Corynebacterium glutamicum, at ∼3 Å resolution is described using a combination of homology modeling with MODELLER, molecular-replacement phasing with Phaser, deformable elastic network (DEN) refinement and automated model building using AutoBuild in a semi-automated fashion, followed by final refinement cycles with phenix.refine and Coot. This difficult molecular-replacement case illustrates the power of including DEN restraints derived from a starting model to guide the movements of the model during refinement. The resulting improved model phases provide better starting points for automated model building and produce more significant difference peaks in anomalous difference Fourier maps to locate anomalous scatterers than does standard refinement. This example also illustrates a current limitation of automated procedures that require manual adjustment of local sequence misalignments between the homology model and the target sequence. PMID:22505259

Exploring Organic Mechanistic Puzzles with Molecular Modeling

ERIC Educational Resources Information Center

Horowitz, Gail; Schwartz, Gary

2004-01-01

The molecular modeling was used to reinforce more general skills such as deducing and drawing reaction mechanisms, analyzing reaction kinetics and thermodynamics and drawing reaction coordinate energy diagrams. This modeling was done through the design of mechanistic puzzles, involving reactions not familiar to the students.

Predictive Finite Rate Model for Oxygen-Carbon Interactions at High Temperature

NASA Astrophysics Data System (ADS)

Poovathingal, Savio

An oxidation model for carbon surfaces is developed to predict ablation rates for carbon heat shields used in hypersonic vehicles. Unlike existing empirical models, the approach used here was to probe gas-surface interactions individually and then based on an understanding of the relevant fundamental processes, build a predictive model that would be accurate over a wide range of pressures and temperatures, and even microstructures. Initially, molecular dynamics was used to understand the oxidation processes on the surface. The molecular dynamics simulations were compared to molecular beam experiments and good qualitative agreement was observed. The simulations reproduced cylindrical pitting observed in the experiments where oxidation was rapid and primarily occurred around a defect. However, the studies were limited to small systems at low temperatures and could simulate time scales only of the order of nanoseconds. Molecular beam experiments at high surface temperature indicated that a majority of surface reaction products were produced through thermal mechanisms. Since the reactions were thermal, they occurred over long time scales which were computationally prohibitive for molecular dynamics to simulate. The experiments provided detailed dynamical data on the scattering of O, O2, CO, and CO2 and it was found that the data from molecular beam experiments could be used directly to build a model. The data was initially used to deduce surface reaction probabilities at 800 K. The reaction probabilities were then incorporated into the direct simulation Monte Carlo (DSMC) method. Simulations were performed where the microstructure was resolved and dissociated oxygen convected and diffused towards it. For a gas-surface temperature of 800 K, it was found that despite CO being the dominant surface reaction product, a gas-phase reaction forms significant CO2 within the microstructure region. It was also found that surface area did not play any role in concentration of reaction products because the reaction probabilities were in the diffusion dominant regime. The molecular beam data at different surface temperatures was then used to build a finite rate model. Each reaction mechanism and all rate parameters of the new model were determined individually based on the molecular beam data. Despite the experiments being performed at near vacuum conditions, the finite rate model developed using the data could be used at pressures and temperatures relevant to hypersonic conditions. The new model was implemented in a computational fluid dynamics (CFD) solver and flow over a hypersonic vehicle was simulated. The new model predicted similar overall mass loss rates compared to existing models, however, the individual species production rates were completely different. The most notable difference was that the new model (based on molecular beam data) predicts CO as the oxidation reaction product with virtually no CO2 production, whereas existing models predict the exact opposite trend. CO being the dominant oxidation product is consistent with recent high enthalpy wind tunnel experiments. The discovery that measurements taken in molecular beam facilities are able to determine individual reaction mechanisms, including dependence on surface coverage, opens up an entirely new way of constructing ablation models.

Conceptual Model-Based Systems Biology: Mapping Knowledge and Discovering Gaps in the mRNA Transcription Cycle

PubMed Central

Somekh, Judith; Choder, Mordechai; Dori, Dov

2012-01-01

We propose a Conceptual Model-based Systems Biology framework for qualitative modeling, executing, and eliciting knowledge gaps in molecular biology systems. The framework is an adaptation of Object-Process Methodology (OPM), a graphical and textual executable modeling language. OPM enables concurrent representation of the system's structure—the objects that comprise the system, and behavior—how processes transform objects over time. Applying a top-down approach of recursively zooming into processes, we model a case in point—the mRNA transcription cycle. Starting with this high level cell function, we model increasingly detailed processes along with participating objects. Our modeling approach is capable of modeling molecular processes such as complex formation, localization and trafficking, molecular binding, enzymatic stimulation, and environmental intervention. At the lowest level, similar to the Gene Ontology, all biological processes boil down to three basic molecular functions: catalysis, binding/dissociation, and transporting. During modeling and execution of the mRNA transcription model, we discovered knowledge gaps, which we present and classify into various types. We also show how model execution enhances a coherent model construction. Identification and pinpointing knowledge gaps is an important feature of the framework, as it suggests where research should focus and whether conjectures about uncertain mechanisms fit into the already verified model. PMID:23308089

Multi-scale modelling of supercapacitors: From molecular simulations to a transmission line model

NASA Astrophysics Data System (ADS)

Pean, C.; Rotenberg, B.; Simon, P.; Salanne, M.

2016-09-01

We perform molecular dynamics simulations of a typical nanoporous-carbon based supercapacitor. The organic electrolyte consists in 1-ethyl-3-methylimidazolium and hexafluorophosphate ions dissolved in acetonitrile. We simulate systems at equilibrium, for various applied voltages. This allows us to determine the relevant thermodynamic (capacitance) and transport (in-pore resistivities) properties. These quantities are then injected in a transmission line model for testing its ability to predict the charging properties of the device. The results from this macroscopic model are in good agreement with non-equilibrium molecular dynamics simulations, which validates its use for interpreting electrochemical impedance experiments.

On the computation of molecular surface correlations for protein docking using fourier techniques.

PubMed

Sakk, Eric

2007-08-01

The computation of surface correlations using a variety of molecular models has been applied to the unbound protein docking problem. Because of the computational complexity involved in examining all possible molecular orientations, the fast Fourier transform (FFT) (a fast numerical implementation of the discrete Fourier transform (DFT)) is generally applied to minimize the number of calculations. This approach is rooted in the convolution theorem which allows one to inverse transform the product of two DFTs in order to perform the correlation calculation. However, such a DFT calculation results in a cyclic or "circular" correlation which, in general, does not lead to the same result as the linear correlation desired for the docking problem. In this work, we provide computational bounds for constructing molecular models used in the molecular surface correlation problem. The derived bounds are then shown to be consistent with various intuitive guidelines previously reported in the protein docking literature. Finally, these bounds are applied to different molecular models in order to investigate their effect on the correlation calculation.

Variational Implicit Solvation with Solute Molecular Mechanics: From Diffuse-Interface to Sharp-Interface Models.

PubMed

Li, Bo; Zhao, Yanxiang

2013-01-01

Central in a variational implicit-solvent description of biomolecular solvation is an effective free-energy functional of the solute atomic positions and the solute-solvent interface (i.e., the dielectric boundary). The free-energy functional couples together the solute molecular mechanical interaction energy, the solute-solvent interfacial energy, the solute-solvent van der Waals interaction energy, and the electrostatic energy. In recent years, the sharp-interface version of the variational implicit-solvent model has been developed and used for numerical computations of molecular solvation. In this work, we propose a diffuse-interface version of the variational implicit-solvent model with solute molecular mechanics. We also analyze both the sharp-interface and diffuse-interface models. We prove the existence of free-energy minimizers and obtain their bounds. We also prove the convergence of the diffuse-interface model to the sharp-interface model in the sense of Γ-convergence. We further discuss properties of sharp-interface free-energy minimizers, the boundary conditions and the coupling of the Poisson-Boltzmann equation in the diffuse-interface model, and the convergence of forces from diffuse-interface to sharp-interface descriptions. Our analysis relies on the previous works on the problem of minimizing surface areas and on our observations on the coupling between solute molecular mechanical interactions with the continuum solvent. Our studies justify rigorously the self consistency of the proposed diffuse-interface variational models of implicit solvation.

wFReDoW: A Cloud-Based Web Environment to Handle Molecular Docking Simulations of a Fully Flexible Receptor Model

PubMed Central

De Paris, Renata; Frantz, Fábio A.; Norberto de Souza, Osmar; Ruiz, Duncan D. A.

2013-01-01

Molecular docking simulations of fully flexible protein receptor (FFR) models are coming of age. In our studies, an FFR model is represented by a series of different conformations derived from a molecular dynamic simulation trajectory of the receptor. For each conformation in the FFR model, a docking simulation is executed and analyzed. An important challenge is to perform virtual screening of millions of ligands using an FFR model in a sequential mode since it can become computationally very demanding. In this paper, we propose a cloud-based web environment, called web Flexible Receptor Docking Workflow (wFReDoW), which reduces the CPU time in the molecular docking simulations of FFR models to small molecules. It is based on the new workflow data pattern called self-adaptive multiple instances (P-SaMIs) and on a middleware built on Amazon EC2 instances. P-SaMI reduces the number of molecular docking simulations while the middleware speeds up the docking experiments using a High Performance Computing (HPC) environment on the cloud. The experimental results show a reduction in the total elapsed time of docking experiments and the quality of the new reduced receptor models produced by discarding the nonpromising conformations from an FFR model ruled by the P-SaMI data pattern. PMID:23691504

Information engineering for molecular diagnostics.

PubMed Central

Sorace, J. M.; Ritondo, M.; Canfield, K.

1994-01-01

Clinical laboratories are beginning to apply the recent advances in molecular biology to the testing of patient samples. The emerging field of Molecular Diagnostics will require a new Molecular Diagnostics Laboratory Information System which handles the data types, samples and test methods found in this field. The system must be very flexible in regards to supporting ad-hoc queries. The requirements which are shaping the developments in this field are reviewed and a data model developed. Several queries which demonstrate the data models ability to support the information needs of this area have been developed and run. These results demonstrate the ability of the purposed data model to meet the current and projected needs of this rapidly expanding field. PMID:7949937

The Effect of Different Molecular Models on High School Students' Conceptions of Molecular Genetics

ERIC Educational Resources Information Center

Rotbain, Yosi; Stavy, Ruth; Marbach-Ad, Gili

2008-01-01

Our main goal in this study was to explore whether the use of models in high school molecular genetics instruction can contribute to students' understanding of concepts and processes in genetics. Three hundred and nineteen students from four comparable groups of 11th- and 12th-grade students participated. The control group (116 students) was…

Coestimation of recombination, substitution and molecular adaptation rates by approximate Bayesian computation.

PubMed

Lopes, J S; Arenas, M; Posada, D; Beaumont, M A

2014-03-01

The estimation of parameters in molecular evolution may be biased when some processes are not considered. For example, the estimation of selection at the molecular level using codon-substitution models can have an upward bias when recombination is ignored. Here we address the joint estimation of recombination, molecular adaptation and substitution rates from coding sequences using approximate Bayesian computation (ABC). We describe the implementation of a regression-based strategy for choosing subsets of summary statistics for coding data, and show that this approach can accurately infer recombination allowing for intracodon recombination breakpoints, molecular adaptation and codon substitution rates. We demonstrate that our ABC approach can outperform other analytical methods under a variety of evolutionary scenarios. We also show that although the choice of the codon-substitution model is important, our inferences are robust to a moderate degree of model misspecification. In addition, we demonstrate that our approach can accurately choose the evolutionary model that best fits the data, providing an alternative for when the use of full-likelihood methods is impracticable. Finally, we applied our ABC method to co-estimate recombination, substitution and molecular adaptation rates from 24 published human immunodeficiency virus 1 coding data sets.

In silico modelling and molecular dynamics simulation studies of thiazolidine based PTP1B inhibitors.

PubMed

Mahapatra, Manoj Kumar; Bera, Krishnendu; Singh, Durg Vijay; Kumar, Rajnish; Kumar, Manoj

2018-04-01

Protein tyrosine phosphatase 1B (PTP1B) has been identified as a negative regulator of insulin and leptin signalling pathway; hence, it can be considered as a new therapeutic target of intervention for the treatment of type 2 diabetes. Inhibition of this molecular target takes care of both diabetes and obesity, i.e. diabestiy. In order to get more information on identification and optimization of lead, pharmacophore modelling, atom-based 3D QSAR, docking and molecular dynamics studies were carried out on a set of ligands containing thiazolidine scaffold. A six-point pharmacophore model consisting of three hydrogen bond acceptor (A), one negative ionic (N) and two aromatic rings (R) with discrete geometries as pharmacophoric features were developed for a predictive 3D QSAR model. The probable binding conformation of the ligands within the active site was studied through molecular docking. The molecular interactions and the structural features responsible for PTP1B inhibition and selectivity were further supplemented by molecular dynamics simulation study for a time scale of 30 ns. The present investigation has identified some of the indispensible structural features of thiazolidine analogues which can further be explored to optimize PTP1B inhibitors.

Coarse gaining of molecular crystals: limitations imposed by molecular flexibility

NASA Astrophysics Data System (ADS)

Picu, Catalin; Pal, Anirban

Molecular crystals include molecular electronics, energetic materials, pharmaceuticals and some food components. In many of these applications the small scale mechanical behavior of the crystal is important such as for example in energetic materials where detonation is induced by the formation of hot spots which are induced thermomechanically, and in pharmaceuticals where phase stability is critical for the biochemical activity of the drug. Accurate modeling of these processes requires resolving the atomistic scale details of the material. However, the cost of these models is very large due to the complexity of the molecules forming the crystal, and some form of coarse graning is necessary. In this study we identify the limitations imposed by the need to accurately capture molecular flexibility on the development of coarse grained models for the energetic molecular crystal RDX. We define guidelines for the definition of coarse grained models that target elastic and plastic crystal scale properties such as elastic constants, thermal expansion, compressibility, the critical stress for the motion of dislocations (Peierls stress) and the stacking fault energy This work was supported by the ARO through Grant W911NF-09-1-0330 and AFRL through Grant FA8651-16-1-0004.

Molecular replacement: tricks and treats

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

Abergel, Chantal, E-mail: chantal.abergel@igs.cnrs-mrs.fr

2013-11-01

To be successful, molecular replacement relies on the quality of the model and of the crystallographic data. Some tricks that could be applied to the models or to the crystal to increase the success rate of MR are discussed here. Molecular replacement is the method of choice for X-ray crystallographic structure determination provided that suitable structural homologues are available in the PDB. Presently, there are ∼80 000 structures in the PDB (8074 were deposited in the year 2012 alone), of which ∼70% have been solved by molecular replacement. For successful molecular replacement the model must cover at least 50% ofmore » the total structure and the C{sub α} r.m.s.d. between the core model and the structure to be solved must be less than 2 Å. Here, an approach originally implemented in the CaspR server (http://www.igs.cnrs-mrs.fr/Caspr2/index.cgi) based on homology modelling to search for a molecular-replacement solution is discussed. How the use of as much information as possible from different sources can improve the model(s) is briefly described. The combination of structural information with distantly related sequences is crucial to optimize the multiple alignment that will define the boundaries of the core domains. PDB clusters (sequences with ≥30% identical residues) can also provide information on the eventual changes in conformation and will help to explore the relative orientations assumed by protein subdomains. Normal-mode analysis can also help in generating series of conformational models in the search for a molecular-replacement solution. Of course, finding a correct solution is only the first step and the accuracy of the identified solution is as important as the data quality to proceed through refinement. Here, some possible reasons for failure are discussed and solutions are proposed using a set of successful examples.« less

Chemical insight from density functional modeling of molecular adsorption: Tracking the bonding and diffusion of anthracene derivatives on Cu(111) with molecular orbitals

NASA Astrophysics Data System (ADS)

Wyrick, Jonathan; Einstein, T. L.; Bartels, Ludwig

2015-03-01

We present a method of analyzing the results of density functional modeling of molecular adsorption in terms of an analogue of molecular orbitals. This approach permits intuitive chemical insight into the adsorption process. Applied to a set of anthracene derivates (anthracene, 9,10-anthraquinone, 9,10-dithioanthracene, and 9,10-diselenonanthracene), we follow the electronic states of the molecules that are involved in the bonding process and correlate them to both the molecular adsorption geometry and the species' diffusive behavior. We additionally provide computational code to easily repeat this analysis on any system.

Atomic and molecular supernovae

NASA Technical Reports Server (NTRS)

Liu, Weihong

1997-01-01

Atomic and molecular physics of supernovae is discussed with an emphasis on the importance of detailed treatments of the critical atomic and molecular processes with the best available atomic and molecular data. The observations of molecules in SN 1987A are interpreted through a combination of spectral and chemical modelings, leading to strong constraints on the mixing and nucleosynthesis of the supernova. The non-equilibrium chemistry is used to argue that carbon dust can form in the oxygen-rich clumps where the efficient molecular cooling makes the nucleation of dust grains possible. For Type Ia supernovae, the analyses of their nebular spectra lead to strong constraints on the supernova explosion models.

Digital Learning Material for Student-Directed Model Building in Molecular Biology

ERIC Educational Resources Information Center

Aegerter-Wilmsen, Tinri; Coppens, Marjolijn; Janssen, Fred; Hartog, Rob; Bisseling, Ton

2005-01-01

The building of models to explain data and make predictions constitutes an important goal in molecular biology research. To give students the opportunity to practice such model building, two digital cases had previously been developed in which students are guided to build a model step by step. In this article, the development and initial…

United polarizable multipole water model for molecular mechanics simulation

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

Qi, Rui; Wang, Qiantao; Ren, Pengyu, E-mail: pren@mail.utexas.edu

2015-07-07

We report the development of a united AMOEBA (uAMOEBA) polarizable water model, which is computationally 3–5 times more efficient than the three-site AMOEBA03 model in molecular dynamics simulations while providing comparable accuracy for gas-phase and liquid properties. In this coarse-grained polarizable water model, both electrostatic (permanent and induced) and van der Waals representations have been reduced to a single site located at the oxygen atom. The permanent charge distribution is described via the molecular dipole and quadrupole moments and the many-body polarization via an isotropic molecular polarizability, all located at the oxygen center. Similarly, a single van der Waals interactionmore » site is used for each water molecule. Hydrogen atoms are retained only for the purpose of defining local frames for the molecular multipole moments and intramolecular vibrational modes. The parameters have been derived based on a combination of ab initio quantum mechanical and experimental data set containing gas-phase cluster structures and energies, and liquid thermodynamic properties. For validation, additional properties including dimer interaction energy, liquid structures, self-diffusion coefficient, and shear viscosity have been evaluated. The results demonstrate good transferability from the gas to the liquid phase over a wide range of temperatures, and from nonpolar to polar environments, due to the presence of molecular polarizability. The water coordination, hydrogen-bonding structure, and dynamic properties given by uAMOEBA are similar to those derived from the all-atom AMOEBA03 model and experiments. Thus, the current model is an accurate and efficient alternative for modeling water.« less

Nonmetallic electronegativity equalization and point-dipole interaction model including exchange interactions for molecular dipole moments and polarizabilities.

PubMed

Smalø, Hans S; Astrand, Per-Olof; Jensen, Lasse

2009-07-28

The electronegativity equalization model (EEM) has been combined with a point-dipole interaction model to obtain a molecular mechanics model consisting of atomic charges, atomic dipole moments, and two-atom relay tensors to describe molecular dipole moments and molecular dipole-dipole polarizabilities. The EEM has been phrased as an atom-atom charge-transfer model allowing for a modification of the charge-transfer terms to avoid that the polarizability approaches infinity for two particles at infinite distance and for long chains. In the present work, these shortcomings have been resolved by adding an energy term for transporting charges through individual atoms. A Gaussian distribution is adopted for the atomic charge distributions, resulting in a damping of the electrostatic interactions at short distances. Assuming that an interatomic exchange term may be described as the overlap between two electronic charge distributions, the EEM has also been extended by a short-range exchange term. The result is a molecular mechanics model where the difference of charge transfer in insulating and metallic systems is modeled regarding the difference in bond length between different types of system. For example, the model is capable of modeling charge transfer in both alkanes and alkenes with alternating double bonds with the same set of carbon parameters only relying on the difference in bond length between carbon sigma- and pi-bonds. Analytical results have been obtained for the polarizability of a long linear chain. These results show that the model is capable of describing the polarizability scaling both linearly and nonlinearly with the size of the system. Similarly, a linear chain with an end atom with a high electronegativity has been analyzed analytically. The dipole moment of this model system can either be independent of the length or increase linearly with the length of the chain. In addition, the model has been parametrized for alkane and alkene chains with data from density functional theory calculations, where the polarizability behaves differently with the chain length. For the molecular dipole moment, the same two systems have been studied with an aldehyde end group. Both the molecular polarizability and the dipole moment are well described as a function of the chain length for both alkane and alkene chains demonstrating the power of the presented model.

TMOD-05. MOLECULAR CHARACTERIZATION OF ORTHOTOPIC PATIENT-DERIVED XENOGRAFT MODELS OF PEDIATRIC BRAIN TUMORS AND THEIR USE IN PRECLINICAL EXPERIMENTS

PubMed Central

Brabetz, Sebastian; Schmidt, Christin; Groebner, Susanne N.; Mack, Norman; Seker-Cin, Huriye; Jones, David T.W.; Chavez, Lukas; Milde, Till; Witt, Olaf; Leary, Sarah E.; Li, Xiao-Nan; Wechsler-Reya, Robert J.; Olson, James M.; Pfister, Stefan M.; Kool, Marcel

2017-01-01

Abstract Genomic studies have shown that multiple molecular subtypes of pediatric brain tumors exist that are biologically and clinically highly distinct. These findings ask for novel subtype specific treatments. To develop these we need more and better preclinical models that correctly reflect the proper tumor (sub)type. Orthotopic patient-derived xenograft (PDX) models generated by intracranial injection of primary patient material into the brain of NSG mice offer the unique possibility to test novel substances in primary patient tissue in an in vivo environment. Prior to drug selection and testing, extensive molecular characterizations of PDX and matching primary tumor/blood (DNA methylation, DNA sequencing, and gene expression) are needed to see how the PDX represents the original disease and to learn about targetable oncogenic drivers in each model. In collaboration with several groups around the world we have generated and fully characterized thus far 75 PDX models reflecting 15 distinct subtypes of pediatric brain cancer. PDX models always retain their molecular subtype and in the vast majority of cases also mutations and copy number alterations compared to matching primary tumors. Most aggressive tumors, harboring MYC(N) amplifications, are overrepresented in the cohort, but also subtypes which have not been available for preclinical testing before due to lack of genetically engineered mouse models or suitable cell lines, such as Group 4 medulloblastoma, are included. All models and corresponding molecular data will become available for the community for preclinical research. Examples of such preclinical experiments will be presented. PDX models of pediatric brain tumors are still quite rare. Our repertoire of PDX models and corresponding molecular characterizations allow researchers all over the world to find the right models for their specific scientific questions. It will provide an unprecedented resource to study tumor biology and pave the way for improving treatment strategies for children with malignant brain tumors.

Tests of potential functional barriers for laminated multilayer food packages. Part II: Medium molecular weight permeants.

PubMed

Simal-Gándara, J; Sarria-Vidal, M; Rijk, R

2000-09-01

Experiments were performed to characterize the kinetics of the permeation of different medium molecular weight model permeants: bisphenol A, warfarin and anthracene, from liquid paraffin, through a surrogate potential functional barrier (25 microns-thick orientated polypropylene--OPP) into the food simulants olive oil and 3% (w/v) acetic acid. The characterization of permeation kinetics generally observed the permeation models previously reported to explain the experimental permeation results obtained for a low molecular weight group of model permeants. In general, the model permeants exhibited behaviour consistent with their relative molecular weights with respect to (a) the time taken to attain steady-state permeation into the food simulant in which they were more soluble, (b) their subsequent steady-state permeation rates, and (c) their partition between liquid paraffin and the OPP membrane.

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

de Miguel, E.; Rull, L.F.; Gubbins, K.E.

Using molecular-dynamics computer simulation, we study the dynamical behavior of the isotropic and nematic phases of highly anisotropic molecular fluids. The interactions are modeled by means of the Gay-Berne potential with anisotropy parameters {kappa}=3 and {kappa}{prime}=5. The linear-velocity autocorrelation function shows no evidence of a negative region in the isotropic phase, even at the higher densities considered. The self-diffusion coefficient parallel to the molecular axis shows an anomalous increase with density as the system enters the nematic region. This enhancement in parallel diffusion is also observed in the isotropic side of the transition as a precursor effect. The molecular reorientationmore » is discussed in the light of different theoretical models. The Debye diffusion model appears to explain the reorientational mechanism in the nematic phase. None of the models gives a satisfactory account of the reorientation process in the isotropic phase.« less

Use of molecular modeling to determine the interaction and competition of gases within coal for carbon dioxide sequestration

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

Jeffrey D. Evanseck; Jeffry D. Madura; Jonathan P. Mathews

2006-04-21

Molecular modeling was employed to both visualize and probe our understanding of carbon dioxide sequestration within a bituminous coal. A large-scale (>20,000 atoms) 3D molecular representation of Pocahontas No. 3 coal was generated. This model was constructed based on a the review data of Stock and Muntean, oxidation and decarboxylation data for aromatic clustersize frequency of Stock and Obeng, and the combination of Laser Desorption Mass Spectrometry data with HRTEM, enabled the inclusion of a molecular weight distribution. The model contains 21,931 atoms, with a molecular mass of 174,873 amu, and an average molecular weight of 714 amu, with 201more » structural components. The structure was evaluated based on several characteristics to ensure a reasonable constitution (chemical and physical representation). The helium density of Pocahontas No. 3 coal is 1.34 g/cm{sup 3} (dmmf) and the model was 1.27 g/cm{sup 3}. The structure is microporous, with a pore volume comprising 34% of the volume as expected for a coal of this rank. The representation was used to visualize CO{sub 2}, and CH{sub 4} capacity, and the role of moisture in swelling and CO{sub 2}, and CH{sub 4} capacity reduction. Inclusion of 0.68% moisture by mass (ash-free) enabled the model to swell by 1.2% (volume). Inclusion of CO{sub 2} enabled volumetric swelling of 4%.« less

Development of bovine serum albumin-water partition coefficients predictive models for ionogenic organic chemicals based on chemical form adjusted descriptors.

PubMed

Ding, Feng; Yang, Xianhai; Chen, Guosong; Liu, Jining; Shi, Lili; Chen, Jingwen

2017-10-01

The partition coefficients between bovine serum albumin (BSA) and water (K BSA/w ) for ionogenic organic chemicals (IOCs) were different greatly from those of neutral organic chemicals (NOCs). For NOCs, several excellent models were developed to predict their logK BSA/w . However, it was found that the conventional descriptors are inappropriate for modeling logK BSA/w of IOCs. Thus, alternative approaches are urgently needed to develop predictive models for K BSA/w of IOCs. In this study, molecular descriptors that can be used to characterize the ionization effects (e.g. chemical form adjusted descriptors) were calculated and used to develop predictive models for logK BSA/w of IOCs. The models developed had high goodness-of-fit, robustness, and predictive ability. The predictor variables selected to construct the models included the chemical form adjusted averages of the negative potentials on the molecular surface (V s-adj - ), the chemical form adjusted molecular dipole moment (dipolemoment adj ), the logarithm of the n-octanol/water distribution coefficient (logD). As these molecular descriptors can be calculated from their molecular structures directly, the developed model can be easily used to fill the logK BSA/w data gap for other IOCs within the applicability domain. Furthermore, the chemical form adjusted descriptors calculated in this study also could be used to construct predictive models on other endpoints of IOCs. Copyright © 2017 Elsevier Inc. All rights reserved.

Molecular Modeling of Nucleic Acid Structure: Electrostatics and Solvation

PubMed Central

Bergonzo, Christina; Galindo-Murillo, Rodrigo; Cheatham, Thomas E.

2014-01-01

This unit presents an overview of computer simulation techniques as applied to nucleic acid systems, ranging from simple in vacuo molecular modeling techniques to more complete all-atom molecular dynamics treatments that include an explicit representation of the environment. The third in a series of four units, this unit focuses on critical issues in solvation and the treatment of electrostatics. UNITS 7.5 & 7.8 introduced the modeling of nucleic acid structure at the molecular level. This included a discussion of how to generate an initial model, how to evaluate the utility or reliability of a given model, and ultimately how to manipulate this model to better understand the structure, dynamics, and interactions. Subject to an appropriate representation of the energy, such as a specifically parameterized empirical force field, the techniques of minimization and Monte Carlo simulation, as well as molecular dynamics (MD) methods, were introduced as means to sample conformational space for a better understanding of the relevance of a given model. From this discussion, the major limitations with modeling, in general, were highlighted. These are the difficult issues in sampling conformational space effectively—the multiple minima or conformational sampling problems—and accurately representing the underlying energy of interaction. In order to provide a realistic model of the underlying energetics for nucleic acids in their native environments, it is crucial to include some representation of solvation (by water) and also to properly treat the electrostatic interactions. These are discussed in detail in this unit. PMID:18428877

Molecular modeling of nucleic Acid structure: electrostatics and solvation.

PubMed

Bergonzo, Christina; Galindo-Murillo, Rodrigo; Cheatham, Thomas E

2014-12-19

This unit presents an overview of computer simulation techniques as applied to nucleic acid systems, ranging from simple in vacuo molecular modeling techniques to more complete all-atom molecular dynamics treatments that include an explicit representation of the environment. The third in a series of four units, this unit focuses on critical issues in solvation and the treatment of electrostatics. UNITS 7.5 & 7.8 introduced the modeling of nucleic acid structure at the molecular level. This included a discussion of how to generate an initial model, how to evaluate the utility or reliability of a given model, and ultimately how to manipulate this model to better understand its structure, dynamics, and interactions. Subject to an appropriate representation of the energy, such as a specifically parameterized empirical force field, the techniques of minimization and Monte Carlo simulation, as well as molecular dynamics (MD) methods, were introduced as a way of sampling conformational space for a better understanding of the relevance of a given model. This discussion highlighted the major limitations with modeling in general. When sampling conformational space effectively, difficult issues are encountered, such as multiple minima or conformational sampling problems, and accurately representing the underlying energy of interaction. In order to provide a realistic model of the underlying energetics for nucleic acids in their native environments, it is crucial to include some representation of solvation (by water) and also to properly treat the electrostatic interactions. These subjects are discussed in detail in this unit. Copyright © 2014 John Wiley & Sons, Inc.

Modeling Aromatic Liquids:  Toluene, Phenol, and Pyridine.

PubMed

Baker, Christopher M; Grant, Guy H

2007-03-01

Aromatic groups are now acknowledged to play an important role in many systems of interest. However, existing molecular mechanics methods provide a poor representation of these groups. In a previous paper, we have shown that the molecular mechanics treatment of benzene can be improved by the incorporation of an explicit representation of the aromatic π electrons. Here, we develop this concept further, developing charge-separation models for toluene, phenol, and pyridine. Monte Carlo simulations are used to parametrize the models, via the reproduction of experimental thermodynamic data, and our models are shown to outperform an existing atom-centered model. The models are then used to make predictions about the structures of the liquids at the molecular level and are tested further through their application to the modeling of gas-phase dimers and cation-π interactions.

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

Antonelli, Perry Edward

A low-level model-to-model interface is presented that will enable independent models to be linked into an integrated system of models. The interface is based on a standard set of functions that contain appropriate export and import schemas that enable models to be linked with no changes to the models themselves. These ideas are presented in the context of a specific multiscale material problem that couples atomistic-based molecular dynamics calculations to continuum calculations of fluid ow. These simulations will be used to examine the influence of interactions of the fluid with an adjacent solid on the fluid ow. The interface willmore » also be examined by adding it to an already existing modeling code, Large-scale Atomic/Molecular Massively Parallel Simulator (LAMMPS) and comparing it with our own molecular dynamics code.« less

Testing the role of molecular physics in dissipative divertor operations through helium plasmas at DIII-D

DOE PAGES

Canik, John M.; Briesemeister, Alexis R.; McLean, Adam G.; ...

2017-05-10

Recent experiments in DIII-D helium plasmas are examined to resolve the role of atomic and molecular physics in major discrepancies between experiment and modeling of dissipative divertor operation. Helium operation removes the complicated molecular processes of deuterium plasmas that are a prime candidate for the inability of standard fluid models to reproduce dissipative divertor operation, primarily the consistent under-prediction of radiated power. Modeling of these experiments shows that the full divertor radiation can be accounted for, but only if measures are taken to ensure that the model reproduces the measured divertor density. Relying on upstream measurements instead results in amore » lower divertor density and radiation than is measured, indicating a need for improved modeling of the connection between the diverter and the upstream scrape-off layer. Furthermore, these results show that fluid models are able to quantitatively describe the divertor-region plasma, including radiative losses, and indicate that efforts to improve the fidelity of the molecular deuterium models are likely to help resolve the discrepancy in radiation for deuterium plasmas.« less

Assessment of Simple Models for Molecular Simulation of Ethylene Carbonate and Propylene Carbonate as Solvents for Electrolyte Solutions.

PubMed

Chaudhari, Mangesh I; Muralidharan, Ajay; Pratt, Lawrence R; Rempe, Susan B

2018-02-12

Progress in understanding liquid ethylene carbonate (EC) and propylene carbonate (PC) on the basis of molecular simulation, emphasizing simple models of interatomic forces, is reviewed. Results on the bulk liquids are examined from the perspective of anticipated applications to materials for electrical energy storage devices. Preliminary results on electrochemical double-layer capacitors based on carbon nanotube forests and on model solid-electrolyte interphase (SEI) layers of lithium ion batteries are considered as examples. The basic results discussed suggest that an empirically parameterized, non-polarizable force field can reproduce experimental structural, thermodynamic, and dielectric properties of EC and PC liquids with acceptable accuracy. More sophisticated force fields might include molecular polarizability and Buckingham-model description of inter-atomic overlap repulsions as extensions to Lennard-Jones models of van der Waals interactions. Simple approaches should be similarly successful also for applications to organic molecular ions in EC/PC solutions, but the important case of Li[Formula: see text] deserves special attention because of the particularly strong interactions of that small ion with neighboring solvent molecules. To treat the Li[Formula: see text] ions in liquid EC/PC solutions, we identify interaction models defined by empirically scaled partial charges for ion-solvent interactions. The empirical adjustments use more basic inputs, electronic structure calculations and ab initio molecular dynamics simulations, and also experimental results on Li[Formula: see text] thermodynamics and transport in EC/PC solutions. Application of such models to the mechanism of Li[Formula: see text] transport in glassy SEI models emphasizes the advantage of long time-scale molecular dynamics studies of these non-equilibrium materials.

High Performance Parallel Computational Nanotechnology

NASA Technical Reports Server (NTRS)

Saini, Subhash; Craw, James M. (Technical Monitor)

1995-01-01

At a recent press conference, NASA Administrator Dan Goldin encouraged NASA Ames Research Center to take a lead role in promoting research and development of advanced, high-performance computer technology, including nanotechnology. Manufacturers of leading-edge microprocessors currently perform large-scale simulations in the design and verification of semiconductor devices and microprocessors. Recently, the need for this intensive simulation and modeling analysis has greatly increased, due in part to the ever-increasing complexity of these devices, as well as the lessons of experiences such as the Pentium fiasco. Simulation, modeling, testing, and validation will be even more important for designing molecular computers because of the complex specification of millions of atoms, thousands of assembly steps, as well as the simulation and modeling needed to ensure reliable, robust and efficient fabrication of the molecular devices. The software for this capacity does not exist today, but it can be extrapolated from the software currently used in molecular modeling for other applications: semi-empirical methods, ab initio methods, self-consistent field methods, Hartree-Fock methods, molecular mechanics; and simulation methods for diamondoid structures. In as much as it seems clear that the application of such methods in nanotechnology will require powerful, highly powerful systems, this talk will discuss techniques and issues for performing these types of computations on parallel systems. We will describe system design issues (memory, I/O, mass storage, operating system requirements, special user interface issues, interconnects, bandwidths, and programming languages) involved in parallel methods for scalable classical, semiclassical, quantum, molecular mechanics, and continuum models; molecular nanotechnology computer-aided designs (NanoCAD) techniques; visualization using virtual reality techniques of structural models and assembly sequences; software required to control mini robotic manipulators for positional control; scalable numerical algorithms for reliability, verifications and testability. There appears no fundamental obstacle to simulating molecular compilers and molecular computers on high performance parallel computers, just as the Boeing 777 was simulated on a computer before manufacturing it.

Optimization of a polymer composite employing molecular mechanic simulations and artificial neural networks for a novel intravaginal bioadhesive drug delivery device.

PubMed

Ndesendo, Valence M K; Pillay, Viness; Choonara, Yahya E; du Toit, Lisa C; Kumar, Pradeep; Buchmann, Eckhart; Meyer, Leith C R; Khan, Riaz A

2012-01-01

This study aimed at elucidating an optimal synergistic polymer composite for achieving a desirable molecular bioadhesivity and Matrix Erosion of a bioactive-loaded Intravaginal Bioadhesive Polymeric Device (IBPD) employing Molecular Mechanic Simulations and Artificial Neural Networks (ANN). Fifteen lead caplet-shaped devices were formulated by direct compression with the model bioactives zidovudine and polystyrene sulfonate. The Matrix Erosion was analyzed in simulated vaginal fluid to assess the critical integrity. Blueprinting the molecular mechanics of bioadhesion between vaginal epithelial glycoprotein (EGP), mucin (MUC) and the IBPD were performed on HyperChem 8.0.8 software (MM+ and AMBER force fields) for the quantification and characterization of correlative molecular interactions during molecular bioadhesion. Results proved that the IBPD bioadhesivity was pivoted on the conformation, orientation, and poly(acrylic acid) (PAA) composition that interacted with EGP and MUC present on the vaginal epithelium due to heterogeneous surface residue distributions (free energy= -46.33 kcalmol(-1)). ANN sensitivity testing as a connectionist model enabled strategic polymer selection for developing an IBPD with an optimally prolonged Matrix Erosion and superior molecular bioadhesivity (ME = 1.21-7.68%; BHN = 2.687-4.981 N/mm(2)). Molecular modeling aptly supported the EGP-MUC-PAA molecular interaction at the vaginal epithelium confirming the role of PAA in bioadhesion of the IBPD once inserted into the posterior fornix of the vagina.

Accelerated molecular dynamics and protein conformational change: a theoretical and practical guide using a membrane embedded model neurotransmitter transporter.

PubMed

Gedeon, Patrick C; Thomas, James R; Madura, Jeffry D

2015-01-01

Molecular dynamics simulation provides a powerful and accurate method to model protein conformational change, yet timescale limitations often prevent direct assessment of the kinetic properties of interest. A large number of molecular dynamic steps are necessary for rare events to occur, which allow a system to overcome energy barriers and conformationally transition from one potential energy minimum to another. For many proteins, the energy landscape is further complicated by a multitude of potential energy wells, each separated by high free-energy barriers and each potentially representative of a functionally important protein conformation. To overcome these obstacles, accelerated molecular dynamics utilizes a robust bias potential function to simulate the transition between different potential energy minima. This straightforward approach more efficiently samples conformational space in comparison to classical molecular dynamics simulation, does not require advanced knowledge of the potential energy landscape and converges to the proper canonical distribution. Here, we review the theory behind accelerated molecular dynamics and discuss the approach in the context of modeling protein conformational change. As a practical example, we provide a detailed, step-by-step explanation of how to perform an accelerated molecular dynamics simulation using a model neurotransmitter transporter embedded in a lipid cell membrane. Changes in protein conformation of relevance to the substrate transport cycle are then examined using principle component analysis.

The structure of PX3 (X = Cl, Br, I) molecular liquids from X-ray diffraction, molecular dynamics simulations, and reverse Monte Carlo modeling.

PubMed

Pothoczki, Szilvia; Temleitner, László; Pusztai, László

2014-02-07

Synchrotron X-ray diffraction measurements have been conducted on liquid phosphorus trichloride, tribromide, and triiodide. Molecular Dynamics simulations for these molecular liquids were performed with a dual purpose: (1) to establish whether existing intermolecular potential functions can provide a picture that is consistent with diffraction data and (2) to generate reliable starting configurations for subsequent Reverse Monte Carlo modelling. Structural models (i.e., sets of coordinates of thousands of atoms) that were fully consistent with experimental diffraction information, within errors, have been prepared by means of the Reverse Monte Carlo method. Comparison with reference systems, generated by hard sphere-like Monte Carlo simulations, was also carried out to demonstrate the extent to which simple space filling effects determine the structure of the liquids (and thus, also estimating the information content of measured data). Total scattering structure factors, partial radial distribution functions and orientational correlations as a function of distances between the molecular centres have been calculated from the models. In general, more or less antiparallel arrangements of the primary molecular axes that are found to be the most favourable orientation of two neighbouring molecules. In liquid PBr3 electrostatic interactions seem to play a more important role in determining intermolecular correlations than in the other two liquids; molecular arrangements in both PCl3 and PI3 are largely driven by steric effects.

Markov state models and molecular alchemy

NASA Astrophysics Data System (ADS)

Schütte, Christof; Nielsen, Adam; Weber, Marcus

2015-01-01

In recent years, Markov state models (MSMs) have attracted a considerable amount of attention with regard to modelling conformation changes and associated function of biomolecular systems. They have been used successfully, e.g. for peptides including time-resolved spectroscopic experiments, protein function and protein folding , DNA and RNA, and ligand-receptor interaction in drug design and more complicated multivalent scenarios. In this article, a novel reweighting scheme is introduced that allows to construct an MSM for certain molecular system out of an MSM for a similar system. This permits studying how molecular properties on long timescales differ between similar molecular systems without performing full molecular dynamics simulations for each system under consideration. The performance of the reweighting scheme is illustrated for simple test cases, including one where the main wells of the respective energy landscapes are located differently and an alchemical transformation of butane to pentane where the dimension of the state space is changed.

Study on the activity of non-purine xanthine oxidase inhibitor by 3D-QSAR modeling and molecular docking

NASA Astrophysics Data System (ADS)

Li, Peizhen; Tian, Yueli; Zhai, Honglin; Deng, Fangfang; Xie, Meihong; Zhang, Xiaoyun

2013-11-01

Non-purine derivatives have been shown to be promising novel drug candidates as xanthine oxidase inhibitors. Based on three-dimensional quantitative structure-activity relationship (3D-QSAR) methods including comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA), two 3D-QSAR models for a series of non-purine xanthine oxidase (XO) inhibitors were established, and their reliability was supported by statistical parameters. Combined 3D-QSAR modeling and the results of molecular docking between non-purine xanthine oxidase inhibitors and XO, the main factors that influenced activity of inhibitors were investigated, and the obtained results could explain known experimental facts. Furthermore, several new potential inhibitors with higher activity predicted were designed, which based on our analyses, and were supported by the simulation of molecular docking. This study provided some useful information for the development of non-purine xanthine oxidase inhibitors with novel structures.

A Mouse Ependymoma Model Provides Molecular Insights into Tumor Formation.

PubMed

Pajtler, Kristian W; Pfister, Stefan M

2018-06-26

Ozawa et al. present a murine tumor model resembling the most frequent molecular group of human supratentorial ependymoma, ST-EPN-RELA. Their model shows RELA-fusion-based de novo ependymoma tumorigenesis in the forebrain derived from neural stem cells. Copyright © 2018. Published by Elsevier Inc.

Reasoning with Atomic-Scale Molecular Dynamic Models

ERIC Educational Resources Information Center

Pallant, Amy; Tinker, Robert F.

2004-01-01

The studies reported in this paper are an initial effort to explore the applicability of computational models in introductory science learning. Two instructional interventions are described that use a molecular dynamics model embedded in a set of online learning activities with middle and high school students in 10 classrooms. The studies indicate…

Learning Molecular Behaviour May Improve Student Explanatory Models of the Greenhouse Effect

ERIC Educational Resources Information Center

Harris, Sara E.; Gold, Anne U.

2018-01-01

We assessed undergraduates' representations of the greenhouse effect, based on student-generated concept sketches, before and after a 30-min constructivist lesson. Principal component analysis of features in student sketches revealed seven distinct and coherent explanatory models including a new "Molecular Details" model. After the…

Testing the molecular clock using mechanistic models of fossil preservation and molecular evolution.

PubMed

Warnock, Rachel C M; Yang, Ziheng; Donoghue, Philip C J

2017-06-28

Molecular sequence data provide information about relative times only, and fossil-based age constraints are the ultimate source of information about absolute times in molecular clock dating analyses. Thus, fossil calibrations are critical to molecular clock dating, but competing methods are difficult to evaluate empirically because the true evolutionary time scale is never known. Here, we combine mechanistic models of fossil preservation and sequence evolution in simulations to evaluate different approaches to constructing fossil calibrations and their impact on Bayesian molecular clock dating, and the relative impact of fossil versus molecular sampling. We show that divergence time estimation is impacted by the model of fossil preservation, sampling intensity and tree shape. The addition of sequence data may improve molecular clock estimates, but accuracy and precision is dominated by the quality of the fossil calibrations. Posterior means and medians are poor representatives of true divergence times; posterior intervals provide a much more accurate estimate of divergence times, though they may be wide and often do not have high coverage probability. Our results highlight the importance of increased fossil sampling and improved statistical approaches to generating calibrations, which should incorporate the non-uniform nature of ecological and temporal fossil species distributions. © 2017 The Authors.

Towards a unifying theory for the first-, second-, and third-order molecular (non)linear optical response

NASA Astrophysics Data System (ADS)

Pérez-Moreno, Javier; Clays, Koen; Kuzyk, Mark G.

2010-05-01

We present a procedure for the modeling of the dispersion of the nonlinear optical response of complex molecular structures that is based strictly on the results from experimental characterization. We show how under some general conditions, the use of the Thomas-Kuhn sum-rules leads to a successful modeling of the nonlinear response of complex molecular structures.

Thermospheric Mass Density Specification: Synthesis of Observations and Models

DTIC Science & Technology

2013-10-21

Simulation Experiments (OSSEs) of the column-integrated ratio of atomic oxygen and molecular nitrogen. Note that OSSEs assimilate, for a given...realistic observing system, synthetically generated observational data often sampled from model simulation results, in place of actually observed values...and molecular oxygen mass mixing ratio). Note that in the TIEGCM the molecular nitrogen mass mixing ratio is specified so that the sum of mixing

Multigrid based First-Principles Molecular Dynamics

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

Fattebert, Jean-Luc; Osei-Kuffuor, Daniel; Dunn, Ian

2017-06-01

MGmol ls a First-Principles Molecular Dynamics code. It relies on the Born-Oppenheimer approximation and models the electronic structure using Density Functional Theory, either LDA or PBE. Norm-conserving pseudopotentials are used to model atomic cores.

Diamond-like nanoparticles influence on flavonoids transport: molecular modelling

NASA Astrophysics Data System (ADS)

Plastun, Inna L.; Agandeeva, Ksenia E.; Bokarev, Andrey N.; Zenkin, Nikita S.

2017-03-01

Intermolecular interaction of diamond-like nanoparticles and flavonoids is investigated by numerical simulation. Using molecular modelling by the density functional theory method, we analyze hydrogen bonds formation and their influence on IR - spectra and structure of molecular complex which is formed due to interaction between flavonoids and nanodiamonds surrounded with carboxylic groups. Enriched adamantane (1,3,5,7 - adamantanetetracarboxylic acid) is used as an example of diamond-like nanoparticles. Intermolecular forces and structure of hydrogen bonds are investigated. IR - spectra and structure parameters of quercetin - adamantanetetracarboxylic acid molecular complex are obtained by numerical simulation using the Gaussian software complex. Received data coincide well with experimental results. Intermolecular interactions and hydrogen bonding structure in the obtained molecular complex are examined. Possibilities of flavonoids interaction with DNA at the molecular level are also considered.

Molecular dynamics, flexible docking, virtual screening, ADMET predictions, and molecular interaction field studies to design novel potential MAO-B inhibitors.

PubMed

Braun, Glaucia H; Jorge, Daniel M M; Ramos, Henrique P; Alves, Raquel M; da Silva, Vinicius B; Giuliatti, Silvana; Sampaio, Suley Vilela; Taft, Carlton A; Silva, Carlos H T P

2008-02-01

Monoamine oxidase is a flavoenzyme bound to the mitochondrial outer membranes of the cells, which is responsible for the oxidative deamination of neurotransmitter and dietary amines. It has two distinct isozymic forms, designated MAO-A and MAO-B, each displaying different substrate and inhibitor specificities. They are the well-known targets for antidepressant, Parkinson's disease, and neuroprotective drugs. Elucidation of the x-ray crystallographic structure of MAO-B has opened the way for the molecular modeling studies. In this work we have used molecular modeling, density functional theory with correlation, virtual screening, flexible docking, molecular dynamics, ADMET predictions, and molecular interaction field studies in order to design new molecules with potential higher selectivity and enzymatic inhibitory activity over MAO-B.

Mirrored continuum and molecular scale simulations of the ignition of gamma phase RDX

NASA Astrophysics Data System (ADS)

Stewart, D. Scott; Chaudhuri, Santanu; Joshi, Kaushik; Lee, Kiabek

2015-06-01

We consider the ignition of a high-pressure gamma-phase of an explosive crystal of RDX which forms during overdriven shock initiation. Molecular dynamics (MD), with first-principles based or reactive force field based molecular potentials, provides a description of the chemistry as an extremely complex reaction network. The results of the molecular simulation is analyzed by sorting molecular product fragments into high and low molecular groups, to represent identifiable components that can be interpreted by a continuum model. A continuum model based on a Gibbs formulation, that has a single temperature and stress state for the mixture is used to represent the same RDX material and its chemistry. Each component in the continuum model has a corresponding Gibbs continuum potential, that are in turn inferred from molecular MD informed equation of state libraries such as CHEETAH, or are directly simulated by Monte Carlo MD simulations. Information about transport, kinetic rates and diffusion are derived from the MD simulation and the growth of a reactive hot spot in the RDX is studied with both simulations that mirror the other results to provide an essential, continuum/atomistic link. Supported by N000014-12-1-0555, subaward-36561937 (ONR).

Dipole-Oriented Molecular Solids Can Undergo a Phase Change and Still Maintain Electrical Polarization

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

Cassidy, Andrew; Jørgensen, Mads R. V.; Rosu-Finsen, Alexander

2016-10-02

It has recently been demonstrated that nanoscale molecular films can spontaneously assemble to self-generate intrinsic electric fields that can exceed 10 8 V/m. These electric fields originate from polarization charges in the material that arise because the films self-assemble to orient molecular dipole moments. This has been called the spontelectric effect. Such growth of spontaneously polarized layers of molecular solids has implications for our understanding of how intermolecular interactions dictate the structure of molecular materials used in a range of applications, for example, molecular semiconductors, sensors, and catalysts. In this paper, we present the first in situ structural characterization ofmore » a representative spontelectric solid, nitrous oxide. Infrared spectroscopy, temperature-programmed desorption, and neutron reflectivity measurements demonstrate that polarized films of nitrous oxide undergo a structural phase transformation upon heating above 48 K. A mean-field model can be used to describe quantitatively the magnitude of the spontaneously generated field as a function of film-growth temperature, and this model also recreates the phase change. Finally, this reinforces the spontelectric model as a means of describing long-range dipole–dipole interactions and points to a new type of ordering in molecular thin films.« less

Mathematical modeling of molecular diffusion through mucus

PubMed Central

Cu, Yen; Saltzman, W. Mark

2008-01-01

The rate of molecular transport through the mucus gel can be an important determinant of efficacy for therapeutic agents delivered by oral, intranasal, intravaginal/rectal, and intraocular routes. Transport through mucus can be described by mathematical models based on principles of physical chemistry and known characteristics of the mucus gel, its constituents, and of the drug itself. In this paper, we review mathematical models of molecular diffusion in mucus, as well as the techniques commonly used to measure diffusion of solutes in the mucus gel, mucus gel mimics, and mucosal epithelia. PMID:19135488

Development of Pantothenate Analogs That Can Treat Combat-Related Infections

DTIC Science & Technology

2014-04-01

determined by the molecular replacement method using the structure of S. aureus PanK excluding bound AMPPNP as a search model ( PDB code 2EWS). The...were solved by molecular replacement using the program PHASER11 and the EcPanK structure as a search model ( PDB : 1SQ5). The models went through...aureus PanK (SaPanK) complexed with N5- Pan (months 1-3) We solved the structure of the SaPanK�N5-Pan complex by the molecular replacement method

Combined HQSAR, topomer CoMFA, homology modeling and docking studies on triazole derivatives as SGLT2 inhibitors.

PubMed

Yu, Shuling; Yuan, Jintao; Zhang, Yi; Gao, Shufang; Gan, Ying; Han, Meng; Chen, Yuewen; Zhou, Qiaoqiao; Shi, Jiahua

2017-06-01

Sodium-glucose cotransporter 2 (SGLT2) is a promising target for diabetes therapy. We aimed to develop computational approaches to identify structural features for more potential SGLT2 inhibitors. In this work, 46 triazole derivatives as SGLT2 inhibitors were studied using a combination of several approaches, including hologram quantitative structure-activity relationships (HQSAR), topomer comparative molecular field analysis (CoMFA), homology modeling, and molecular docking. HQSAR and topomer CoMFA were used to construct models. Molecular docking was conducted to investigate the interaction of triazole derivatives and homology modeling of SGLT2, as well as to validate the results of the HQSAR and topomer CoMFA models. The most effective HQSAR and topomer CoMFA models exhibited noncross-validated correlation coefficients of 0.928 and 0.891 for the training set, respectively. External predictions were made successfully on a test set and then compared with previously reported models. The graphical results of HQSAR and topomer CoMFA were proven to be consistent with the binding mode of the inhibitors and SGLT2 from molecular docking. The models and docking provided important insights into the design of potent inhibitors for SGLT2.

In silico modelling of thiazolidine derivatives with antioxidant potency: Models quantify the degree of contribution of molecular fragments towards the free radical scavenging ability

NASA Astrophysics Data System (ADS)

De, Biplab; Adhikari, Indrani; Nandy, Ashis; Saha, Achintya; Goswami, Binoy Behari

2017-06-01

Design and development of antioxidant supplements constitute an essential aspect of research in order to derive molecules that would help to combat the free radical invasion to the human body and curb oxidative stress related diseases. The present work deals with the development of in silico models for a series of thiazolidine derivatives having antioxidant potential. The objective of the work is to obtain models that would help to design new thazolidine derivatives based on substituent modification and thereby predict their activity profile. The QSAR model thus developed helps in quantification of the extent of contribution of the various molecular fragments towards the activity of the molecules, while the 3D pharmacophore model provides a brief idea of the essential molecular features that help the molecules to interact with the neighbouring free radicals. Both the models have been extensively validated which ensures their predictive ability as well the potential to search molecular databases for selection of thiazolidine derivatives with potent antioxidant activity. The models can thus be utilised effectively for database searching with the aim to isolate active antioxidants belonging to the thiazolidine group.

A Model of How Different Biology Experts Explain Molecular and Cellular Mechanisms

PubMed Central

Trujillo, Caleb M.; Anderson, Trevor R.; Pelaez, Nancy J.

2015-01-01

Constructing explanations is an essential skill for all science learners. The goal of this project was to model the key components of expert explanation of molecular and cellular mechanisms. As such, we asked: What is an appropriate model of the components of explanation used by biology experts to explain molecular and cellular mechanisms? Do explanations made by experts from different biology subdisciplines at a university support the validity of this model? Guided by the modeling framework of R. S. Justi and J. K. Gilbert, the validity of an initial model was tested by asking seven biologists to explain a molecular mechanism of their choice. Data were collected from interviews, artifacts, and drawings, and then subjected to thematic analysis. We found that biologists explained the specific activities and organization of entities of the mechanism. In addition, they contextualized explanations according to their biological and social significance; integrated explanations with methods, instruments, and measurements; and used analogies and narrated stories. The derived methods, analogies, context, and how themes informed the development of our final MACH model of mechanistic explanations. Future research will test the potential of the MACH model as a guiding framework for instruction to enhance the quality of student explanations. PMID:25999313

The nearly neutral and selection theories of molecular evolution under the fisher geometrical framework: substitution rate, population size, and complexity.

PubMed

Razeto-Barry, Pablo; Díaz, Javier; Vásquez, Rodrigo A

2012-06-01

The general theories of molecular evolution depend on relatively arbitrary assumptions about the relative distribution and rate of advantageous, deleterious, neutral, and nearly neutral mutations. The Fisher geometrical model (FGM) has been used to make distributions of mutations biologically interpretable. We explored an FGM-based molecular model to represent molecular evolutionary processes typically studied by nearly neutral and selection models, but in which distributions and relative rates of mutations with different selection coefficients are a consequence of biologically interpretable parameters, such as the average size of the phenotypic effect of mutations and the number of traits (complexity) of organisms. A variant of the FGM-based model that we called the static regime (SR) represents evolution as a nearly neutral process in which substitution rates are determined by a dynamic substitution process in which the population's phenotype remains around a suboptimum equilibrium fitness produced by a balance between slightly deleterious and slightly advantageous compensatory substitutions. As in previous nearly neutral models, the SR predicts a negative relationship between molecular evolutionary rate and population size; however, SR does not have the unrealistic properties of previous nearly neutral models such as the narrow window of selection strengths in which they work. In addition, the SR suggests that compensatory mutations cannot explain the high rate of fixations driven by positive selection currently found in DNA sequences, contrary to what has been previously suggested. We also developed a generalization of SR in which the optimum phenotype can change stochastically due to environmental or physiological shifts, which we called the variable regime (VR). VR models evolution as an interplay between adaptive processes and nearly neutral steady-state processes. When strong environmental fluctuations are incorporated, the process becomes a selection model in which evolutionary rate does not depend on population size, but is critically dependent on the complexity of organisms and mutation size. For SR as well as VR we found that key parameters of molecular evolution are linked by biological factors, and we showed that they cannot be fixed independently by arbitrary criteria, as has usually been assumed in previous molecular evolutionary models.

The Nearly Neutral and Selection Theories of Molecular Evolution Under the Fisher Geometrical Framework: Substitution Rate, Population Size, and Complexity

PubMed Central

Razeto-Barry, Pablo; Díaz, Javier; Vásquez, Rodrigo A.

2012-01-01

The general theories of molecular evolution depend on relatively arbitrary assumptions about the relative distribution and rate of advantageous, deleterious, neutral, and nearly neutral mutations. The Fisher geometrical model (FGM) has been used to make distributions of mutations biologically interpretable. We explored an FGM-based molecular model to represent molecular evolutionary processes typically studied by nearly neutral and selection models, but in which distributions and relative rates of mutations with different selection coefficients are a consequence of biologically interpretable parameters, such as the average size of the phenotypic effect of mutations and the number of traits (complexity) of organisms. A variant of the FGM-based model that we called the static regime (SR) represents evolution as a nearly neutral process in which substitution rates are determined by a dynamic substitution process in which the population’s phenotype remains around a suboptimum equilibrium fitness produced by a balance between slightly deleterious and slightly advantageous compensatory substitutions. As in previous nearly neutral models, the SR predicts a negative relationship between molecular evolutionary rate and population size; however, SR does not have the unrealistic properties of previous nearly neutral models such as the narrow window of selection strengths in which they work. In addition, the SR suggests that compensatory mutations cannot explain the high rate of fixations driven by positive selection currently found in DNA sequences, contrary to what has been previously suggested. We also developed a generalization of SR in which the optimum phenotype can change stochastically due to environmental or physiological shifts, which we called the variable regime (VR). VR models evolution as an interplay between adaptive processes and nearly neutral steady-state processes. When strong environmental fluctuations are incorporated, the process becomes a selection model in which evolutionary rate does not depend on population size, but is critically dependent on the complexity of organisms and mutation size. For SR as well as VR we found that key parameters of molecular evolution are linked by biological factors, and we showed that they cannot be fixed independently by arbitrary criteria, as has usually been assumed in previous molecular evolutionary models. PMID:22426879

Peridynamics with LAMMPS : a user guide.

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

Lehoucq, Richard B.; Silling, Stewart Andrew; Plimpton, Steven James

2008-01-01

Peridynamics is a nonlocal formulation of continuum mechanics. The discrete peridynamic model has the same computational structure as a molecular dynamic model. This document details the implementation of a discrete peridynamic model within the LAMMPS molecular dynamic code. This document provides a brief overview of the peridynamic model of a continuum, then discusses how the peridynamic model is discretized, and overviews the LAMMPS implementation. A nontrivial example problem is also included.

Molecular clouds and galactic spiral structure

NASA Technical Reports Server (NTRS)

Dame, T. M.

1984-01-01

Galactic CO line emission at 115 GHz was surveyed in order to study the distribution of molecular clouds in the inner galaxy. Comparison of this survey with similar H1 data reveals a detailed correlation with the most intense 21 cm features. To each of the classical 21 cm H1 spiral arms of the inner galaxy there corresponds a CO molecular arm which is generally more clearly defined and of higher contrast. A simple model is devised for the galactic distribution of molecular clouds. The modeling results suggest that molecular clouds are essentially transient objects, existing for 15 to 40 million years after their formation in a spiral arm, and are largely confined to spiral features about 300 pc wide.

Molecular graph convolutions: moving beyond fingerprints

NASA Astrophysics Data System (ADS)

Kearnes, Steven; McCloskey, Kevin; Berndl, Marc; Pande, Vijay; Riley, Patrick

2016-08-01

Molecular "fingerprints" encoding structural information are the workhorse of cheminformatics and machine learning in drug discovery applications. However, fingerprint representations necessarily emphasize particular aspects of the molecular structure while ignoring others, rather than allowing the model to make data-driven decisions. We describe molecular graph convolutions, a machine learning architecture for learning from undirected graphs, specifically small molecules. Graph convolutions use a simple encoding of the molecular graph—atoms, bonds, distances, etc.—which allows the model to take greater advantage of information in the graph structure. Although graph convolutions do not outperform all fingerprint-based methods, they (along with other graph-based methods) represent a new paradigm in ligand-based virtual screening with exciting opportunities for future improvement.

Molecular graph convolutions: moving beyond fingerprints.

PubMed

Kearnes, Steven; McCloskey, Kevin; Berndl, Marc; Pande, Vijay; Riley, Patrick

2016-08-01

Molecular "fingerprints" encoding structural information are the workhorse of cheminformatics and machine learning in drug discovery applications. However, fingerprint representations necessarily emphasize particular aspects of the molecular structure while ignoring others, rather than allowing the model to make data-driven decisions. We describe molecular graph convolutions, a machine learning architecture for learning from undirected graphs, specifically small molecules. Graph convolutions use a simple encoding of the molecular graph-atoms, bonds, distances, etc.-which allows the model to take greater advantage of information in the graph structure. Although graph convolutions do not outperform all fingerprint-based methods, they (along with other graph-based methods) represent a new paradigm in ligand-based virtual screening with exciting opportunities for future improvement.

Special conference of the American Association for Cancer Research on molecular imaging in cancer: linking biology, function, and clinical applications in vivo.

PubMed

Luker, Gary D

2002-04-01

The AACR Special Conference on Molecular Imaging in Cancer: Linking Biology, Function, and Clinical Applications In Vivo, was held January 23-27, 2002, at the Contemporary Hotel, Walt Disney World, Orlando, FL. Co-Chairs David Piwnica-Worms, Patricia Price and Thomas Meade brought together researchers with diverse expertise in molecular biology, gene therapy, chemistry, engineering, pharmacology, and imaging to accelerate progress in developing and applying technologies for imaging specific cellular and molecular signals in living animals and humans. The format of the conference was the presentation of research that focused on basic and translational biology of cancer and current state-of-the-art techniques for molecular imaging in animal models and humans. This report summarizes the special conference on molecular imaging, highlighting the interfaces of molecular biology with animal models, instrumentation, chemistry, and pharmacology that are essential to convert the dreams and promise of molecular imaging into improved understanding, diagnosis, and management of cancer.

Principles that Govern the Performance of Molecular Motors

NASA Astrophysics Data System (ADS)

Eide, Jon; Chakraborty, Arup; Oster, George

2003-03-01

We have created a two dimensional polymeric coarse-grained model to simulate the power stroke from the F0F1 ATP synthase class of molecular motors. There has been much work to understand the structure and dynamics of this type of molecular motor using both constrained molecular dynamics and general Markov models but neither of them have been able to elucidate in a qualitative manner how a constant force is created and transferred in the motor at a nearly 100efficiency. Our model is a modified Rouse system using Brownian and Monte Carlo (with solvent) Dynamics, concentrating only on the catalytic site and protein structures that we think are important for motor motion and energy transfer. While modeling the real system as closely as possible, we have determined the optimum characteristics for maximum efficiency. The efficiency depends on the load against the polymer, the polymer flexibility, polymer and surface matching, and solvent interactions. Insight into the basic principles behind the mechanical motion of this system may have implications for many other molecular motors driven by nucleotide hydrolysis and help design synthetic devices that can carry out biomimetic tasks.

Clinically compatible flexible wide-field multi-color fluorescence endoscopy with a porcine colon model

PubMed Central

Oh, Gyugnseok; Park, Youngrong; Yoo, Su Woong; Hwang, Soonjoo; Chin-Yu, Alexey V. Dan; Ryu, Yeon-Mi; Kim, Sang-Yeob; Do, Eun-Ju; Kim, Ki Hean; Kim, Sungjee; Myung, Seung-Jae; Chung, Euiheon

2017-01-01

Early detection of structural or molecular changes in dysplastic epithelial tissues is crucial for cancer screening and surveillance. Multi-targeting molecular endoscopic fluorescence imaging may improve noninvasive detection of precancerous lesions in the colon. Here, we report the first clinically compatible, wide-field-of-view, multi-color fluorescence endoscopy with a leached fiber bundle scope using a porcine model. A porcine colon model that resembles the human colon is used for the detection of surrogate tumors composed of multiple biocompatible fluorophores (FITC, ICG, and heavy metal-free quantum dots (hfQDs)). With an ex vivo porcine colon tumor model, molecular imaging with hfQDs conjugated with MMP14 antibody was achieved by spraying molecular probes on a mucosa layer that contains xenograft tumors. With an in vivo porcine colon embedded with surrogate tumors, target-to-background ratios of 3.36 ± 0.43, 2.70 ± 0.72, and 2.10 ± 0.13 were achieved for FITC, ICG, and hfQD probes, respectively. This promising endoscopic technology with molecular contrast shows the capacity to reveal hidden tumors and guide treatment strategy decisions. PMID:28270983

Molecular model for the diffusion of associating telechelic polymer networks

NASA Astrophysics Data System (ADS)

Ramirez, Jorge; Dursch, Thomas; Olsen, Bradley

Understanding the mechanisms of motion and stress relaxation of associating polymers at the molecular level is critical for advanced technological applications such as enhanced oil-recovery, self-healing materials or drug delivery. In associating polymers, the strength and rates of association/dissociation of the reversible physical crosslinks govern the dynamics of the network and therefore all the macroscopic properties, like self-diffusion and rheology. Recently, by means of forced Rayleigh scattering experiments, we have proved that associating polymers of different architectures show super-diffusive behavior when the free motion of single molecular species is slowed down by association/dissociation kinetics. Here we discuss a new molecular picture for unentangled associating telechelic polymers that considers concentration, molecular weight, number of arms of the molecules and equilibrium and rate constants of association/dissociation. The model predicts super-diffusive behavior under the right combination of values of the parameters. We discuss some of the predictions of the model using scaling arguments, show detailed results from Brownian dynamics simulations of the FRS experiments, and attempt to compare the predictions of the model to experimental data.

Melting Behavior of a Model Molecular Crystalline GeI4

NASA Astrophysics Data System (ADS)

Fuchizaki, Kazuhiro; Asano, Yuta

2015-06-01

A model molecular crystalline GeI4 was examined using molecular dynamics simulation. The model was constructed in such a way that rigid tetrahedral molecules interact with each other via Lennard-Jones potentials whose centers are located at the vertices of a tetrahedron. Because no other interaction that can "soften" the intermolecular interaction was introduced, the melting curve of the model crystalline material does not exhibit the anomaly that was found for the real substance. However, the current investigation is useful in that it could settle the upper bound of pressure below which the model can predict properties of the molecular liquid. Moreover, singularity-free nature of the melting curve allowed us to analytically treat the melting curve in the light of the Kumari-Dass-Kechin equation. As a result, we could definitely conclude that the well-known Simon equation for the melting curve is merely an approximate expression. The condition for the validity of Simon's equation was identified.

The effect of the Mihalas, Hummer, and Daeppen equation of state and the molecular opacity on the standard solar model

NASA Technical Reports Server (NTRS)

Kim, Y.-C.; Demarque, P.; Guenther, D. B.

1991-01-01

Improvements to the Yale Rotating Stellar Evolution Code (YREC) by incorporating the Mihalas-Hummer-Daeppen equation of state, an improved opacity interpolation routine, and the effects of molecular opacities, calculated at Los Alamos, have been made. the effect of each of the improvements on the standard solar model has been tested independently by computing the corresponding solar nonradial oscillation frequencies. According to these tests, the Mihalas-Hummer-Daeppen equation of state has very little effect on the model's low l p-mode oscillation spectrum compared to the model using the existing analytical equation of state implemented in YREC. On the other hand, the molecular opacity does improve the model's oscillation spectrum. The effect of molecular opacity on the computed solar oscillation frequencies is much larger than that of the Mihalas-Hummer-Daeppen equation of state. together, the two improvements to the physics reduce the discrepancy with observations by 10 microHz for the low l modes.

Developing model asphalt systems using molecular simulation : final model.

DOT National Transportation Integrated Search

2009-09-01

Computer based molecular simulations have been used towards developing simple mixture compositions whose : physical properties resemble those of real asphalts. First, Monte Carlo simulations with the OPLS all-atom force : field were used to predict t...

Molecular Mechanisms of ZnO Nanoparticle Dispersion in Solution: Modeling of Surfactant Association, Electrostatic Shielding and Counter Ion Dynamics.

PubMed

Duchstein, Patrick; Milek, Theodor; Zahn, Dirk

2015-01-01

Molecular models of 5 nm sized ZnO/Zn(OH)2 core-shell nanoparticles in ethanolic solution were derived as scale-up models (based on an earlier model created from ion-by-ion aggregation and self-organization) and subjected to mechanistic analyses of surface stabilization by block-copolymers. The latter comprise a poly-methacrylate chain accounting for strong surfactant association to the nanoparticle by hydrogen bonding and salt-bridges. While dangling poly-ethylene oxide chains provide only a limited degree of sterical hindering to nanoparticle agglomeration, the key mechanism of surface stabilization is electrostatic shielding arising from the acrylates and a halo of Na+ counter ions associated to the nanoparticle. Molecular dynamics simulations reveal different solvent shells and distance-dependent mobility of ions and solvent molecules. From this, we provide a molecular rationale of effective particle size, net charge and polarizability of the nanoparticles in solution.

Molecular Mechanisms of ZnO Nanoparticle Dispersion in Solution: Modeling of Surfactant Association, Electrostatic Shielding and Counter Ion Dynamics

PubMed Central

Duchstein, Patrick; Milek, Theodor; Zahn, Dirk

2015-01-01

Molecular models of 5 nm sized ZnO/Zn(OH)2 core-shell nanoparticles in ethanolic solution were derived as scale-up models (based on an earlier model created from ion-by-ion aggregation and self-organization) and subjected to mechanistic analyses of surface stabilization by block-copolymers. The latter comprise a poly-methacrylate chain accounting for strong surfactant association to the nanoparticle by hydrogen bonding and salt-bridges. While dangling poly-ethylene oxide chains provide only a limited degree of sterical hindering to nanoparticle agglomeration, the key mechanism of surface stabilization is electrostatic shielding arising from the acrylates and a halo of Na+ counter ions associated to the nanoparticle. Molecular dynamics simulations reveal different solvent shells and distance-dependent mobility of ions and solvent molecules. From this, we provide a molecular rationale of effective particle size, net charge and polarizability of the nanoparticles in solution. PMID:25962096

The emerging role of cloud computing in molecular modelling.

PubMed

Ebejer, Jean-Paul; Fulle, Simone; Morris, Garrett M; Finn, Paul W

2013-07-01

There is a growing recognition of the importance of cloud computing for large-scale and data-intensive applications. The distinguishing features of cloud computing and their relationship to other distributed computing paradigms are described, as are the strengths and weaknesses of the approach. We review the use made to date of cloud computing for molecular modelling projects and the availability of front ends for molecular modelling applications. Although the use of cloud computing technologies for molecular modelling is still in its infancy, we demonstrate its potential by presenting several case studies. Rapid growth can be expected as more applications become available and costs continue to fall; cloud computing can make a major contribution not just in terms of the availability of on-demand computing power, but could also spur innovation in the development of novel approaches that utilize that capacity in more effective ways. Copyright © 2013 Elsevier Inc. All rights reserved.

Evolution of mechanical response of sodium montmorillonite interlayer with increasing hydration by molecular dynamics.

PubMed

Schmidt, Steven R; Katti, Dinesh R; Ghosh, Pijush; Katti, Kalpana S

2005-08-16

The mechanical response of the interlayer of hydrated montmorillonite was evaluated using steered molecular dynamics. An atomic model of the sodium montmorillonite was previously constructed. In the current study, the interlayer of the model was hydrated with multiple layers of water. Using steered molecular dynamics, external forces were applied to individual atoms of the clay surface, and the response of the model was studied. The displacement versus applied stress and stress versus strain relationships of various parts of the interlayer were studied. The paper describes the construction of the model, the simulation procedure, and results of the simulations. Some results of the previous work are further interpreted in the light of the current research. The simulations provide quantitative stress deformation relationships as well as an insight into the molecular interactions taking place between the clay surface and interlayer water and cations.

LAMMPS integrated materials engine (LIME) for efficient automation of particle-based simulations: application to equation of state generation

NASA Astrophysics Data System (ADS)

Barnes, Brian C.; Leiter, Kenneth W.; Becker, Richard; Knap, Jaroslaw; Brennan, John K.

2017-07-01

We describe the development, accuracy, and efficiency of an automation package for molecular simulation, the large-scale atomic/molecular massively parallel simulator (LAMMPS) integrated materials engine (LIME). Heuristics and algorithms employed for equation of state (EOS) calculation using a particle-based model of a molecular crystal, hexahydro-1,3,5-trinitro-s-triazine (RDX), are described in detail. The simulation method for the particle-based model is energy-conserving dissipative particle dynamics, but the techniques used in LIME are generally applicable to molecular dynamics simulations with a variety of particle-based models. The newly created tool set is tested through use of its EOS data in plate impact and Taylor anvil impact continuum simulations of solid RDX. The coarse-grain model results from LIME provide an approach to bridge the scales from atomistic simulations to continuum simulations.

An Evaluation of Explicit Receptor Flexibility in Molecular Docking Using Molecular Dynamics and Torsion Angle Molecular Dynamics.

PubMed

Armen, Roger S; Chen, Jianhan; Brooks, Charles L

2009-10-13

Incorporating receptor flexibility into molecular docking should improve results for flexible proteins. However, the incorporation of explicit all-atom flexibility with molecular dynamics for the entire protein chain may also introduce significant error and "noise" that could decrease docking accuracy and deteriorate the ability of a scoring function to rank native-like poses. We address this apparent paradox by comparing the success of several flexible receptor models in cross-docking and multiple receptor ensemble docking for p38α mitogen-activated protein (MAP) kinase. Explicit all-atom receptor flexibility has been incorporated into a CHARMM-based molecular docking method (CDOCKER) using both molecular dynamics (MD) and torsion angle molecular dynamics (TAMD) for the refinement of predicted protein-ligand binding geometries. These flexible receptor models have been evaluated, and the accuracy and efficiency of TAMD sampling is directly compared to MD sampling. Several flexible receptor models are compared, encompassing flexible side chains, flexible loops, multiple flexible backbone segments, and treatment of the entire chain as flexible. We find that although including side chain and some backbone flexibility is required for improved docking accuracy as expected, docking accuracy also diminishes as additional and unnecessary receptor flexibility is included into the conformational search space. Ensemble docking results demonstrate that including protein flexibility leads to to improved agreement with binding data for 227 active compounds. This comparison also demonstrates that a flexible receptor model enriches high affinity compound identification without significantly increasing the number of false positives from low affinity compounds.

An Evaluation of Explicit Receptor Flexibility in Molecular Docking Using Molecular Dynamics and Torsion Angle Molecular Dynamics

PubMed Central

Armen, Roger S.; Chen, Jianhan; Brooks, Charles L.

2009-01-01

Incorporating receptor flexibility into molecular docking should improve results for flexible proteins. However, the incorporation of explicit all-atom flexibility with molecular dynamics for the entire protein chain may also introduce significant error and “noise” that could decrease docking accuracy and deteriorate the ability of a scoring function to rank native-like poses. We address this apparent paradox by comparing the success of several flexible receptor models in cross-docking and multiple receptor ensemble docking for p38α mitogen-activated protein (MAP) kinase. Explicit all-atom receptor flexibility has been incorporated into a CHARMM-based molecular docking method (CDOCKER) using both molecular dynamics (MD) and torsion angle molecular dynamics (TAMD) for the refinement of predicted protein-ligand binding geometries. These flexible receptor models have been evaluated, and the accuracy and efficiency of TAMD sampling is directly compared to MD sampling. Several flexible receptor models are compared, encompassing flexible side chains, flexible loops, multiple flexible backbone segments, and treatment of the entire chain as flexible. We find that although including side chain and some backbone flexibility is required for improved docking accuracy as expected, docking accuracy also diminishes as additional and unnecessary receptor flexibility is included into the conformational search space. Ensemble docking results demonstrate that including protein flexibility leads to to improved agreement with binding data for 227 active compounds. This comparison also demonstrates that a flexible receptor model enriches high affinity compound identification without significantly increasing the number of false positives from low affinity compounds. PMID:20160879

Molecular modeling-driven approach for identification of Janus kinase 1 inhibitors through 3D-QSAR, docking and molecular dynamics simulations.

PubMed

Itteboina, Ramesh; Ballu, Srilata; Sivan, Sree Kanth; Manga, Vijjulatha

2017-10-01

Janus kinase 1 (JAK 1) belongs to the JAK family of intracellular nonreceptor tyrosine kinase. JAK-signal transducer and activator of transcription (JAK-STAT) pathway mediate signaling by cytokines, which control survival, proliferation and differentiation of a variety of cells. Three-dimensional quantitative structure activity relationship (3 D-QSAR), molecular docking and molecular dynamics (MD) methods was carried out on a dataset of Janus kinase 1(JAK 1) inhibitors. Ligands were constructed and docked into the active site of protein using GLIDE 5.6. Best docked poses were selected after analysis for further 3 D-QSAR analysis using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) methodology. Employing 60 molecules in the training set, 3 D-QSAR models were generate that showed good statistical reliability, which is clearly observed in terms of r 2 ncv and q 2 loo values. The predictive ability of these models was determined using a test set of 25 molecules that gave acceptable predictive correlation (r 2 Pred ) values. The key amino acid residues were identified by means of molecular docking, and the stability and rationality of the derived molecular conformations were also validated by MD simulation. The good consonance between the docking results and CoMFA/CoMSIA contour maps provides helpful clues about the reasonable modification of molecules in order to design more efficient JAK 1 inhibitors. The developed models are expected to provide some directives for further synthesis of highly effective JAK 1 inhibitors.

Use of Molecular Models for Active Learning in Biochemistry Lecture Courses

ERIC Educational Resources Information Center

Hageman, James H.

2010-01-01

The pedagogical value of having biochemistry and organic chemistry students build and manipulate physical models of chemical species is well established in the literature. Nevertheless, for the most part, the use of molecular models is generally limited to several laboratory exercises or to demonstrations in the classroom setting. A simple…

Manipulating 3D-Printed and Paper Models Enhances Student Understanding of Viral Replication

ERIC Educational Resources Information Center

Couper, Lisa; Johannes, Kristen; Powers, Jackie; Silberglitt, Matt; Davenport, Jodi

2016-01-01

Understanding key concepts in molecular biology requires reasoning about molecular processes that are not directly observable and, as such, presents a challenge to students and teachers. We ask whether novel interactive physical models and activities can help students understand key processes in viral replication. Our 3D tangible models are…

The physics of interstellar shock waves

NASA Technical Reports Server (NTRS)

Shull, J. Michael; Draine, Bruce T.

1987-01-01

This review discusses the observations and theoretical models of interstellar shock waves, in both diffuse cloud and molecular cloud environments. It summarizes the relevant gas dynamics, atomic, molecular and grain processes, radiative transfer, and physics of radiative and magnetic precursors in shock models. It then describes the importance of shocks for observations, diagnostics, and global interstellar dynamics. It concludes with current research problems and data needs for atomic, molecular and grain physics.

Ratios of molecular hydrogen line intensities in shocked gas - Evidence for cooling zones

NASA Technical Reports Server (NTRS)

Brand, P. W. J. L.; Moorhouse, A.; Bird, M.; Burton, M. G.; Geballe, T. R.

1988-01-01

Column densities of molecular hydrogen have been calculated from 19 infrared vibration-rotation and pure rotational line intensities measured at peak 1 of the Orion molecular outflow. The run of column density with energy level is similar to a simple coolng zone model of the line-emitting region, but is not well fitted by predictions of C-shock models current in the literature.

In Silico Analyses of Substrate Interactions with Human Serum Paraoxonase 1

DTIC Science & Technology

2008-01-01

substrate interactions of HuPON1 remains elusive. In this study, we apply homology modeling, docking, and molecular dynamic (MD) simulations to probe the...mod- eling; docking; molecular dynamics simulations ; binding free energy decomposition. 486 PROTEINS Published 2008 WILEY-LISS, INC. yThis article is a...apply homology modeling, docking, and molecular dynamic (MD) simulations to probe the binding interactions of HuPON1 with representative substrates. The

Coarse-Grained Lattice Model Simulations of Sequence-Structure Fitness of a Ribosome-Inactivating Protein

DTIC Science & Technology

2007-11-05

limits of what is considered practical when applying all-atom molecular - dynamics simulation methods. Lattice models provide computationally robust...of expectation values from the density of states. All-atom molecular - dynamics simulations provide the most rigorous sampling method to generate con... molecular - dynamics simulations of protein folding,6–9 reported studies of computing a heat capacity or other calorimetric observables have been limited to

Molecular adaptation in Rubisco: Discriminating between convergent evolution and positive selection using mechanistic and classical codon models.

PubMed

Parto, Sahar; Lartillot, Nicolas

2018-01-01

Rubisco (Ribulose-1, 5-biphosphate carboxylase/oxygenase) is the most important enzyme on earth, catalyzing the first step of photosynthetic CO2 fixation. So, without it, there would be no storing of the sun's energy in plants. Molecular adaptation of Rubisco to C4 photosynthetic pathway has attracted a lot of attention. C4 plants, which comprise less than 5% of land plants, have evolved more efficient photosynthesis compared to C3 plants. Interestingly, a large number of independent transitions from C3 to C4 phenotype have occurred. Each time, the Rubisco enzyme has been subject to similar changes in selective pressure, thus providing an excellent model for convergent evolution at the molecular level. Molecular adaptation is often identified with positive selection and is typically characterized by an elevated ratio of non-synonymous to synonymous substitution rate (dN/dS). However, convergent adaptation is expected to leave a different molecular signature, taking the form of repeated transitions toward identical or similar amino acids. Here, we used a previously introduced codon-based differential-selection model to detect and quantify consistent patterns of convergent adaptation in Rubisco in eudicots. We further contrasted our results with those obtained by classical codon models based on the estimation of dN/dS. We found that the two classes of models tend to select distinct, although overlapping, sets of positions. This discrepancy in the results illustrates the conceptual difference between these models while emphasizing the need to better discriminate between qualitatively different selective regimes, by using a broader class of codon models than those currently considered in molecular evolutionary studies.

The Abundance of Molecular Hydrogen and Its Correlation with Midplane Pressure in Galaxies: Non-equilibrium, Turbulent, Chemical Models

NASA Astrophysics Data System (ADS)

Mac Low, Mordecai-Mark; Glover, Simon C. O.

2012-02-01

Observations of spiral galaxies show a strong linear correlation between the ratio of molecular to atomic hydrogen surface density R mol and midplane pressure. To explain this, we simulate three-dimensional, magnetized turbulence, including simplified treatments of non-equilibrium chemistry and the propagation of dissociating radiation, to follow the formation of H2 from cold atomic gas. The formation timescale for H2 is sufficiently long that equilibrium is not reached within the 20-30 Myr lifetimes of molecular clouds. The equilibrium balance between radiative dissociation and H2 formation on dust grains fails to predict the time-dependent molecular fractions we find. A simple, time-dependent model of H2 formation can reproduce the gross behavior, although turbulent density perturbations increase molecular fractions by a factor of few above it. In contradiction to equilibrium models, radiative dissociation of molecules plays little role in our model for diffuse radiation fields with strengths less than 10 times that of the solar neighborhood, because of the effective self-shielding of H2. The observed correlation of R mol with pressure corresponds to a correlation with local gas density if the effective temperature in the cold neutral medium of galactic disks is roughly constant. We indeed find such a correlation of R mol with density. If we examine the value of R mol in our local models after a free-fall time at their average density, as expected for models of molecular cloud formation by large-scale gravitational instability, our models reproduce the observed correlation over more than an order-of-magnitude range in density.

Progress toward bridging from atomistic to continuum modeling to predict nuclear waste glass dissolution.

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

Zapol, Peter; Bourg, Ian; Criscenti, Louise Jacqueline

2011-10-01

This report summarizes research performed for the Nuclear Energy Advanced Modeling and Simulation (NEAMS) Subcontinuum and Upscaling Task. The work conducted focused on developing a roadmap to include molecular scale, mechanistic information in continuum-scale models of nuclear waste glass dissolution. This information is derived from molecular-scale modeling efforts that are validated through comparison with experimental data. In addition to developing a master plan to incorporate a subcontinuum mechanistic understanding of glass dissolution into continuum models, methods were developed to generate constitutive dissolution rate expressions from quantum calculations, force field models were selected to generate multicomponent glass structures and gel layers,more » classical molecular modeling was used to study diffusion through nanopores analogous to those in the interfacial gel layer, and a micro-continuum model (K{mu}C) was developed to study coupled diffusion and reaction at the glass-gel-solution interface.« less

Animal Models of Depression: Molecular Perspectives

PubMed Central

Krishnan, Vaishnav; Nestler, Eric J.

2012-01-01

Much of the current understanding about the pathogenesis of altered mood, impaired concentration and neurovegetative symptoms in major depression has come from animal models. However, because of the unique and complex features of human depression, the generation of valid and insightful depression models has been less straightforward than modeling other disabling diseases like cancer or autoimmune conditions. Today’s popular depression models creatively merge ethologically valid behavioral assays with the latest technological advances in molecular biology and automated video-tracking. This chapter reviews depression assays involving acute stress (e.g., forced swim test), models consisting of prolonged physical or social stress (e.g., social defeat), models of secondary depression, genetic models, and experiments designed to elucidate the mechanisms of antidepressant action. These paradigms are critically evaluated in relation to their ease, validity and replicability, the molecular insights that they have provided, and their capacity to offer the next generation of therapeutics for depression. PMID:21225412

DNA-binding study of anticancer drug cytarabine by spectroscopic and molecular docking techniques.

PubMed

Shahabadi, Nahid; Falsafi, Monireh; Maghsudi, Maryam

2017-01-02

The interaction of anticancer drug cytarabine with calf thymus DNA (CT-DNA) was investigated in vitro under simulated physiological conditions by multispectroscopic techniques and molecular modeling study. The fluorescence spectroscopy and UV absorption spectroscopy indicated drug interacted with CT-DNA in a groove-binding mode, while the binding constant of UV-vis and the number of binding sites were 4.0 ± 0.2 × 10 4 L mol -1 and 1.39, respectively. The fluorimetric studies showed that the reaction between the drugs with CT-DNA is exothermic. Circular dichroism spectroscopy was employed to measure the conformational change of DNA in the presence of cytarabine. Furthermore, the drug induces detectable changes in its viscosity for DNA interaction. The molecular modeling results illustrated that cytarabine strongly binds to groove of DNA by relative binding energy of docked structure -20.61 KJ mol -1 . This combination of multiple spectroscopic techniques and molecular modeling methods can be widely used in the investigation on the interaction of small molecular pollutants and drugs with biomacromolecules for clarifying the molecular mechanism of toxicity or side effect in vivo.

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.

Live Imaging of Centriole Dynamics by Fluorescently Tagged Proteins in Starfish Oocyte Meiosis.

PubMed

Borrego-Pinto, Joana; Somogyi, Kálmán; Lénárt, Péter

2016-01-01

High throughput DNA sequencing, the decreasing costs of DNA synthesis, and universal techniques for genetic manipulation have made it much easier and quicker to establish molecular tools for any organism than it has been 5 years ago. This opens a great opportunity for reviving "nonconventional" model organisms, which are particularly suited to study a specific biological process and many of which have already been established before the era of molecular biology. By taking advantage of transcriptomics, in particular, these systems can now be easily turned into full fetched models for molecular cell biology.As an example, here we describe how we established molecular tools in the starfish Patiria miniata, which has been a popular model for cell and developmental biology due to the synchronous and rapid development, transparency, and easy handling of oocytes, eggs, and embryos. Here, we detail how we used a de novo assembled transcriptome to produce molecular markers and established conditions for live imaging to investigate the molecular mechanisms underlying centriole elimination-a poorly understood process essential for sexual reproduction of animal species.

Submillisecond elastic recoil reveals molecular origins of fibrin fiber mechanics.

PubMed

Hudson, Nathan E; Ding, Feng; Bucay, Igal; O'Brien, E Timothy; Gorkun, Oleg V; Superfine, Richard; Lord, Susan T; Dokholyan, Nikolay V; Falvo, Michael R

2013-06-18

Fibrin fibers form the structural scaffold of blood clots. Thus, their mechanical properties are of central importance to understanding hemostasis and thrombotic disease. Recent studies have revealed that fibrin fibers are elastomeric despite their high degree of molecular ordering. These results have inspired a variety of molecular models for fibrin's elasticity, ranging from reversible protein unfolding to rubber-like elasticity. An important property that has not been explored is the timescale of elastic recoil, a parameter that is critical for fibrin's mechanical function and places a temporal constraint on molecular models of fiber elasticity. Using high-frame-rate imaging and atomic force microscopy-based nanomanipulation, we measured the recoil dynamics of individual fibrin fibers and found that the recoil was orders of magnitude faster than anticipated from models involving protein refolding. We also performed steered discrete molecular-dynamics simulations to investigate the molecular origins of the observed recoil. Our results point to the unstructured αC regions of the otherwise structured fibrin molecule as being responsible for the elastic recoil of the fibers. Copyright © 2013 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Submillisecond Elastic Recoil Reveals Molecular Origins of Fibrin Fiber Mechanics

PubMed Central

Hudson, Nathan E.; Ding, Feng; Bucay, Igal; O’Brien, E. Timothy; Gorkun, Oleg V.; Superfine, Richard; Lord, Susan T.; Dokholyan, Nikolay V.; Falvo, Michael R.

2013-01-01

Fibrin fibers form the structural scaffold of blood clots. Thus, their mechanical properties are of central importance to understanding hemostasis and thrombotic disease. Recent studies have revealed that fibrin fibers are elastomeric despite their high degree of molecular ordering. These results have inspired a variety of molecular models for fibrin’s elasticity, ranging from reversible protein unfolding to rubber-like elasticity. An important property that has not been explored is the timescale of elastic recoil, a parameter that is critical for fibrin’s mechanical function and places a temporal constraint on molecular models of fiber elasticity. Using high-frame-rate imaging and atomic force microscopy-based nanomanipulation, we measured the recoil dynamics of individual fibrin fibers and found that the recoil was orders of magnitude faster than anticipated from models involving protein refolding. We also performed steered discrete molecular-dynamics simulations to investigate the molecular origins of the observed recoil. Our results point to the unstructured αC regions of the otherwise structured fibrin molecule as being responsible for the elastic recoil of the fibers. PMID:23790375

Molecular and functional aspects of menstruation in the macaque.

PubMed

Brenner, Robert M; Slayden, Ov D

2012-12-01

Much of our understanding of the molecular control of menstruation arises from laboratory models that experimentally recapitulate some, but not all, aspects of uterine bleeding observed in women. These models include: in vitro culture of endometrial explants or isolated endometrial cells, transplantation of human endometrial tissue into immunodeficient mice and the induction of endometrial breakdown in appropriately pretreated mice. Each of these models has contributed to our understanding of molecular and cellular mechanisms of menstruation, but nonhuman primates, especially macaques, are the animal model of choice for evaluating therapies for menstrual disorders. In this chapter we review some basic aspects of menstruation, with special emphasis on the macaque model and its relevance to the clinical issues of irregular and heavy menstrual bleeding (HMB).

Molecular Weight and Molecular Weight Distributions in Synthetic Polymers.

ERIC Educational Resources Information Center

Ward, Thomas Carl

1981-01-01

Focuses on molecular weight and molecular weight distributions (MWD) and models for predicting MWD in a pedagogical way. In addition, instrumental methods used to characterize MWD are reviewed with emphasis on physical chemistry of each, including end-group determination, osmometry, light scattering, solution viscosity, fractionation, and…

Bottom-up derivation of conservative and dissipative interactions for coarse-grained molecular liquids with the conditional reversible work method

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

Deichmann, Gregor; Marcon, Valentina; Vegt, Nico F. A. van der, E-mail: vandervegt@csi.tu-darmstadt.de

Molecular simulations of soft matter systems have been performed in recent years using a variety of systematically coarse-grained models. With these models, structural or thermodynamic properties can be quite accurately represented while the prediction of dynamic properties remains difficult, especially for multi-component systems. In this work, we use constraint molecular dynamics simulations for calculating dissipative pair forces which are used together with conditional reversible work (CRW) conservative forces in dissipative particle dynamics (DPD) simulations. The combined CRW-DPD approach aims to extend the representability of CRW models to dynamic properties and uses a bottom-up approach. Dissipative pair forces are derived frommore » fluctuations of the direct atomistic forces between mapped groups. The conservative CRW potential is obtained from a similar series of constraint dynamics simulations and represents the reversible work performed to couple the direct atomistic interactions between the mapped atom groups. Neopentane, tetrachloromethane, cyclohexane, and n-hexane have been considered as model systems. These molecular liquids are simulated with atomistic molecular dynamics, coarse-grained molecular dynamics, and DPD. We find that the CRW-DPD models reproduce the liquid structure and diffusive dynamics of the liquid systems in reasonable agreement with the atomistic models when using single-site mapping schemes with beads containing five or six heavy atoms. For a two-site representation of n-hexane (3 carbons per bead), time scale separation can no longer be assumed and the DPD approach consequently fails to reproduce the atomistic dynamics.« less

Multiscale Modeling of Mesoscale and Interfacial Phenomena

NASA Astrophysics Data System (ADS)

Petsev, Nikolai Dimitrov

With rapidly emerging technologies that feature interfaces modified at the nanoscale, traditional macroscopic models are pushed to their limits to explain phenomena where molecular processes can play a key role. Often, such problems appear to defy explanation when treated with coarse-grained continuum models alone, yet remain prohibitively expensive from a molecular simulation perspective. A prominent example is surface nanobubbles: nanoscopic gaseous domains typically found on hydrophobic surfaces that have puzzled researchers for over two decades due to their unusually long lifetimes. We show how an entirely macroscopic, non-equilibrium model explains many of their anomalous properties, including their stability and abnormally small gas-side contact angles. From this purely transport perspective, we investigate how factors such as temperature and saturation affect nanobubbles, providing numerous experimentally testable predictions. However, recent work also emphasizes the relevance of molecular-scale phenomena that cannot be described in terms of bulk phases or pristine interfaces. This is true for nanobubbles as well, whose nanoscale heights may require molecular detail to capture the relevant physics, in particular near the bubble three-phase contact line. Therefore, there is a clear need for general ways to link molecular granularity and behavior with large-scale continuum models in the treatment of many interfacial problems. In light of this, we have developed a general set of simulation strategies that couple mesoscale particle-based continuum models to molecular regions simulated through conventional molecular dynamics (MD). In addition, we derived a transport model for binary mixtures that opens the possibility for a wide range of applications in biological and drug delivery problems, and is readily reconciled with our hybrid MD-continuum techniques. Approaches that couple multiple length scales for fluid mixtures are largely absent in the literature, and we provide a novel and general framework for multiscale modeling of systems featuring one or more dissolved species. This makes it possible to retain molecular detail for parts of the problem that require it while using a simple, continuum description for parts where high detail is unnecessary, reducing the number of degrees of freedom (i.e. number of particles) dramatically. This opens the possibility for modeling ion transport in biological processes and biomolecule assembly in ionic solution, as well as electrokinetic phenomena at interfaces such as corrosion. The number of particles in the system is further reduced through an integrated boundary approach, which we apply to colloidal suspensions. In this thesis, we describe this general framework for multiscale modeling single- and multicomponent systems, provide several simple equilibrium and non-equilibrium case studies, and discuss future applications.

Computational Molecular Modeling for Evaluating the Toxicity of Environmental Chemicals: Prioritizing Bioassay Requirements

EPA Science Inventory

This commentary provides an overview of the challenges that arise from applying molecular modeling tools developed and commonly used for pharmaceutical discovery to the problem of predicting the potential toxicities of environmental chemicals.

Quantum Mechanics/Molecular Mechanics Method Combined with Hybrid All-Atom and Coarse-Grained Model: Theory and Application on Redox Potential Calculations.

PubMed

Shen, Lin; Yang, Weitao

2016-04-12

We developed a new multiresolution method that spans three levels of resolution with quantum mechanical, atomistic molecular mechanical, and coarse-grained models. The resolution-adapted all-atom and coarse-grained water model, in which an all-atom structural description of the entire system is maintained during the simulations, is combined with the ab initio quantum mechanics and molecular mechanics method. We apply this model to calculate the redox potentials of the aqueous ruthenium and iron complexes by using the fractional number of electrons approach and thermodynamic integration simulations. The redox potentials are recovered in excellent accordance with the experimental data. The speed-up of the hybrid all-atom and coarse-grained water model renders it computationally more attractive. The accuracy depends on the hybrid all-atom and coarse-grained water model used in the combined quantum mechanical and molecular mechanical method. We have used another multiresolution model, in which an atomic-level layer of water molecules around redox center is solvated in supramolecular coarse-grained waters for the redox potential calculations. Compared with the experimental data, this alternative multilayer model leads to less accurate results when used with the coarse-grained polarizable MARTINI water or big multipole water model for the coarse-grained layer.

Large-Scale Atomic/Molecular Massively Parallel Simulator (LAMMPS) Simulations of the Molecular Crystal alphaRDX

DTIC Science & Technology

2013-08-01

potential for HMX / RDX (3, 9). ...................................................................................8 1 1. Purpose This work...6 dispersion and electrostatic interactions. Constants for the SB potential are given in table 1. 8 Table 1. SB potential for HMX / RDX (3, 9...modeling dislocations in the energetic molecular crystal RDX using the Large-Scale Atomic/Molecular Massively Parallel Simulator (LAMMPS) molecular

Agent-Based Modeling in Molecular Systems Biology.

PubMed

Soheilypour, Mohammad; Mofrad, Mohammad R K

2018-07-01

Molecular systems orchestrating the biology of the cell typically involve a complex web of interactions among various components and span a vast range of spatial and temporal scales. Computational methods have advanced our understanding of the behavior of molecular systems by enabling us to test assumptions and hypotheses, explore the effect of different parameters on the outcome, and eventually guide experiments. While several different mathematical and computational methods are developed to study molecular systems at different spatiotemporal scales, there is still a need for methods that bridge the gap between spatially-detailed and computationally-efficient approaches. In this review, we summarize the capabilities of agent-based modeling (ABM) as an emerging molecular systems biology technique that provides researchers with a new tool in exploring the dynamics of molecular systems/pathways in health and disease. © 2018 WILEY Periodicals, Inc.

Molecular and cellular alterations in Down syndrome: toward the identification of targets for therapeutics.

PubMed

Créau, Nicole

2012-01-01

Down syndrome is a complex disease that has challenged molecular and cellular research for more than 50 years. Understanding the molecular bases of morphological, cellular, and functional alterations resulting from the presence of an additional complete chromosome 21 would aid in targeting specific genes and pathways for rescuing some phenotypes. Recently, progress has been made by characterization of brain alterations in mouse models of Down syndrome. This review will highlight the main molecular and cellular findings recently described for these models, particularly with respect to their relationship to Down syndrome phenotypes.

Advances in visual representation of molecular potentials.

PubMed

Du, Qi-Shi; Huang, Ri-Bo; Chou, Kuo-Chen

2010-06-01

The recent advances in visual representations of molecular properties in 3D space are summarized, and their applications in molecular modeling study and rational drug design are introduced. The visual representation methods provide us with detailed insights into protein-ligand interactions, and hence can play a major role in elucidating the structure or reactivity of a biomolecular system. Three newly developed computation and visualization methods for studying the physical and chemical properties of molecules are introduced, including their electrostatic potential, lipophilicity potential and excess chemical potential. The newest application examples of visual representations in structure-based rational drug are presented. The 3D electrostatic potentials, calculated using the empirical method (EM-ESP), in which the classical Coulomb equation and traditional atomic partial changes are discarded, are highly consistent with the results by the higher level quantum chemical method. The 3D lipophilicity potentials, computed by the heuristic molecular lipophilicity potential method based on the principles of quantum mechanics and statistical mechanics, are more accurate and reliable than those by using the traditional empirical methods. The 3D excess chemical potentials, derived by the reference interaction site model-hypernetted chain theory, provide a new tool for computational chemistry and molecular modeling. For structure-based drug design, the visual representations of molecular properties will play a significant role in practical applications. It is anticipated that the new advances in computational chemistry will stimulate the development of molecular modeling methods, further enriching the visual representation techniques for rational drug design, as well as other relevant fields in life science.

Equations of state for hydrogen and deuterium.

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

Kerley, Gerald Irwin

2003-12-01

This report describes the complete revision of a deuterium equation of state (EOS) model published in 1972. It uses the same general approach as the 1972 EOS, i.e., the so-called 'chemical model,' but incorporates a number of theoretical advances that have taken place during the past thirty years. Three phases are included: a molecular solid, an atomic solid, and a fluid phase consisting of both molecular and atomic species. Ionization and the insulator-metal transition are also included. The most important improvements are in the liquid perturbation theory, the treatment of molecular vibrations and rotations, and the ionization equilibrium and mixturemore » models. In addition, new experimental data and theoretical calculations are used to calibrate certain model parameters, notably the zero-Kelvin isotherms for the molecular and atomic solids, and the quantum corrections to the liquid phase. The report gives a general overview of the model, followed by detailed discussions of the most important theoretical issues and extensive comparisons with the many experimental data that have been obtained during the last thirty years. Questions about the validity of the chemical model are also considered. Implications for modeling the 'giant planets' are also discussed.« less

Molecular Volumes and the Stokes-Einstein Equation

ERIC Educational Resources Information Center

Edward, John T.

1970-01-01

Examines the limitations of the Stokes-Einstein equation as it applies to small solute molecules. Discusses molecular volume determinations by atomic increments, molecular models, molar volumes of solids and liquids, and molal volumes. Presents an empirical correction factor for the equation which applies to molecular radii as small as 2 angstrom…

Polymer Fluid Dynamics: Continuum and Molecular Approaches.

PubMed

Bird, R B; Giacomin, A J

2016-06-07

To solve problems in polymer fluid dynamics, one needs the equations of continuity, motion, and energy. The last two equations contain the stress tensor and the heat-flux vector for the material. There are two ways to formulate the stress tensor: (a) One can write a continuum expression for the stress tensor in terms of kinematic tensors, or (b) one can select a molecular model that represents the polymer molecule and then develop an expression for the stress tensor from kinetic theory. The advantage of the kinetic theory approach is that one gets information about the relation between the molecular structure of the polymers and the rheological properties. We restrict the discussion primarily to the simplest stress tensor expressions or constitutive equations containing from two to four adjustable parameters, although we do indicate how these formulations may be extended to give more complicated expressions. We also explore how these simplest expressions are recovered as special cases of a more general framework, the Oldroyd 8-constant model. Studying the simplest models allows us to discover which types of empiricisms or molecular models seem to be worth investigating further. We also explore equivalences between continuum and molecular approaches. We restrict the discussion to several types of simple flows, such as shearing flows and extensional flows, which are of greatest importance in industrial operations. Furthermore, if these simple flows cannot be well described by continuum or molecular models, then it is not necessary to lavish time and energy to apply them to more complex flow problems.

Direct calculation of ice homogeneous nucleation rate for a molecular model of water.

PubMed

Haji-Akbari, Amir; Debenedetti, Pablo G

2015-08-25

Ice formation is ubiquitous in nature, with important consequences in a variety of environments, including biological cells, soil, aircraft, transportation infrastructure, and atmospheric clouds. However, its intrinsic kinetics and microscopic mechanism are difficult to discern with current experiments. Molecular simulations of ice nucleation are also challenging, and direct rate calculations have only been performed for coarse-grained models of water. For molecular models, only indirect estimates have been obtained, e.g., by assuming the validity of classical nucleation theory. We use a path sampling approach to perform, to our knowledge, the first direct rate calculation of homogeneous nucleation of ice in a molecular model of water. We use TIP4P/Ice, the most accurate among existing molecular models for studying ice polymorphs. By using a novel topological approach to distinguish different polymorphs, we are able to identify a freezing mechanism that involves a competition between cubic and hexagonal ice in the early stages of nucleation. In this competition, the cubic polymorph takes over because the addition of new topological structural motifs consistent with cubic ice leads to the formation of more compact crystallites. This is not true for topological hexagonal motifs, which give rise to elongated crystallites that are not able to grow. This leads to transition states that are rich in cubic ice, and not the thermodynamically stable hexagonal polymorph. This mechanism provides a molecular explanation for the earlier experimental and computational observations of the preference for cubic ice in the literature.

Direct calculation of ice homogeneous nucleation rate for a molecular model of water

PubMed Central

Haji-Akbari, Amir; Debenedetti, Pablo G.

2015-01-01

Ice formation is ubiquitous in nature, with important consequences in a variety of environments, including biological cells, soil, aircraft, transportation infrastructure, and atmospheric clouds. However, its intrinsic kinetics and microscopic mechanism are difficult to discern with current experiments. Molecular simulations of ice nucleation are also challenging, and direct rate calculations have only been performed for coarse-grained models of water. For molecular models, only indirect estimates have been obtained, e.g., by assuming the validity of classical nucleation theory. We use a path sampling approach to perform, to our knowledge, the first direct rate calculation of homogeneous nucleation of ice in a molecular model of water. We use TIP4P/Ice, the most accurate among existing molecular models for studying ice polymorphs. By using a novel topological approach to distinguish different polymorphs, we are able to identify a freezing mechanism that involves a competition between cubic and hexagonal ice in the early stages of nucleation. In this competition, the cubic polymorph takes over because the addition of new topological structural motifs consistent with cubic ice leads to the formation of more compact crystallites. This is not true for topological hexagonal motifs, which give rise to elongated crystallites that are not able to grow. This leads to transition states that are rich in cubic ice, and not the thermodynamically stable hexagonal polymorph. This mechanism provides a molecular explanation for the earlier experimental and computational observations of the preference for cubic ice in the literature. PMID:26240318

Molecular design of anticancer drug leads based on three-dimensional quantitative structure-activity relationship.

PubMed

Huang, Xiao Yan; Shan, Zhi Jie; Zhai, Hong Lin; Li, Li Na; Zhang, Xiao Yun

2011-08-22

Heat shock protein 90 (Hsp90) takes part in the developments of several cancers. Novobiocin, a typically C-terminal inhibitor for Hsp90, will probably used as an important anticancer drug in the future. In this work, we explored the valuable information and designed new novobiocin derivatives based on a three-dimensional quantitative structure-activity relationship (3D QSAR). The comparative molecular field analysis and comparative molecular similarity indices analysis models with high predictive capability were established, and their reliabilities are supported by the statistical parameters. Based on the several important influence factors obtained from these models, six new novobiocin derivatives with higher inhibitory activities were designed and confirmed by the molecular simulation with our models, which provide the potential anticancer drug leads for further research.

Computer-aided design of polymers and composites

NASA Technical Reports Server (NTRS)

Kaelble, D. H.

1985-01-01

This book on computer-aided design of polymers and composites introduces and discusses the subject from the viewpoint of atomic and molecular models. Thus, the origins of stiffness, strength, extensibility, and fracture toughness in composite materials can be analyzed directly in terms of chemical composition and molecular structure. Aspects of polymer composite reliability are considered along with characterization techniques for composite reliability, relations between atomic and molecular properties, computer aided design and manufacture, polymer CAD/CAM models, and composite CAD/CAM models. Attention is given to multiphase structural adhesives, fibrous composite reliability, metal joint reliability, polymer physical states and transitions, chemical quality assurance, processability testing, cure monitoring and management, nondestructive evaluation (NDE), surface NDE, elementary properties, ionic-covalent bonding, molecular analysis, acid-base interactions, the manufacturing science, and peel mechanics.

Electronic excitations in molecular solids: bridging theory and experiment.

PubMed

Skelton, Jonathan M; da Silva, E Lora; Crespo-Otero, Rachel; Hatcher, Lauren E; Raithby, Paul R; Parker, Stephen C; Walsh, Aron

2015-01-01

As the spatial and temporal resolution accessible to experiment and theory converge, computational chemistry is an increasingly powerful tool for modelling and interpreting spectroscopic data. However, the study of molecular processes, in particular those related to electronic excitations (e.g. photochemistry), frequently pushes quantum-chemical techniques to their limit. The disparity in the level of theory accessible to periodic and molecular calculations presents a significant challenge when modelling molecular crystals, since accurate calculations require a high level of theory to describe the molecular species, but must also take into account the influence of the crystalline environment on their properties. In this article, we briefly review the different classes of quantum-chemical techniques, and present an overview of methods that account for environmental influences with varying levels of approximation. Using a combination of solid-state and molecular calculations, we quantitatively evaluate the performance of implicit-solvent models for the [Ni(Et4dien)(η2-O,ON)(η1-NO2)] linkage-isomer system as a test case. We focus particularly on the accurate reproduction of the energetics of the isomerisation, and on predicting spectroscopic properties to compare with experimental results. This work illustrates how the synergy between periodic and molecular calculations can be exploited for the study of molecular crystals, and forms a basis for the investigation of more challenging phenomena, such as excited-state dynamics, and for further methodological developments.

Gas-grain chemical models of star-forming molecular clouds as constrained by ISO and SWAS observations

NASA Astrophysics Data System (ADS)

Charnley, S. B.; Rodgers, S. D.; Ehrenfreund, P.

2001-11-01

We have investigated the gaseous and solid state molecular composition of dense interstellar material that periodically experiences processing in the shock waves associated with ongoing star formation. Our motivation is to confront these models with the stringent abundance constraints on CO2, H2O and O2, in both gas and solid phases, that have been set by ISO and SWAS. We also compare our results with the chemical composition of dark molecular clouds as determined by ground-based telescopes. Beginning with the simplest possible model needed to study molecular cloud gas-grain chemistry, we only include additional processes where they are clearly required to satisfy one or more of the ISO-SWAS constraints. When CO, N2 and atoms of N, C and S are efficiently desorbed from grains, a chemical quasi-steady-state develops after about one million years. We find that accretion of CO2 and H2O cannot explain the [CO2/H2O]ice ISO observations; as with previous models, accretion and reaction of oxygen atoms are necessary although a high O atom abundance can still be derived from the CO that remains in the gas. The observational constraints on solid and gaseous molecular oxygen are both met in this model. However, we find that we cannot explain the lowest H2O abundances seen by SWAS or the highest atomic carbon abundances found in molecular clouds; additional chemical processes are required and possible candidates are given. One prediction of models of this type is that there should be some regions of molecular clouds which contain high gas phase abundances of H2O, O2 and NO. A further consequence, we find, is that interstellar grain mantles could be rich in NH2OH and NO2. The search for these regions, as well as NH2OH and NO2 in ices and in hot cores, is an important further test of this scenario. The model can give good agreement with observations of simple molecules in dark molecular clouds such as TMC-1 and L134N. Despite the fact that S atoms are assumed to be continously desorbed from grain surfaces, we find that the sulphur chemistry independently experiences an ``accretion catastrophe''. The S-bearing molecular abundances cease to lie within the observed range after about 3 x 106 years and this indicates that there may be at least two efficient surface desorption mechanisms operating in dark clouds - one quasi-continous and the other operating more sporadically on this time-scale. We suggest that mantle removal on short time-scales is mediated by clump dynamics, and by the effects of star formation on longer time-scales. The applicability of this type of dynamical-chemical model for molecular cloud evolution is discussed and comparison is made with other models of dark cloud chemistry.

Modeling Far-UV Fluorescent Emission Features of Warm Molecular Hydrogen in the Inner Regions of Protoplanetary Disks

NASA Astrophysics Data System (ADS)

Hoadley, Keri; France, Kevin

2015-01-01

Probing the surviving molecular gas within the inner regions of protoplanetary disks (PPDs) around T Tauri stars (1 - 10 Myr) provides insight into the conditions in which planet formation and migration occurs while the gas disk is still present. We model observed far ultraviolet (FUV) molecular hydrogen (H₂) fluorescent emission lines that originate within the inner regions (< 10 AU) of 9 well-studied Classic T Tauri stars, using the Hubble Space Telescope Cosmic Origins Spectrograph (COS), to explore the physical structure of the molecular disk at different PPD dust evolutionary stages. We created a 2D radiative transfer model that estimates the density and temperature distributions of warm, inner radial H₂ (T > 1500 K) with a set of 6 free parameters and produces a data cube of expected emission line profiles that describe the physical structure of the inner molecular disk atmosphere. By comparing the modeled emission lines with COS H₂ fluorescence emission features, we estimate the physical structure of the molecular disk atmosphere for each target with the set of free parameters that best replicate the observed lines. First results suggest that, for all dust evolutionary stages of disks considered, ground-state H₂ populations are described by a roughly constant temperature T(H₂) = 2500 +/- 1000 K. Possible evolution of the density structure of the H₂ atmosphere between intact and depleting dust disks may be distinguishable, but large errors in the inferred best-fit parameter sets prevent us from making this conclusion. Further improvements to the modeling framework and statistical comparison in determining the best-fit model-to-data parameter sets are ongoing, beginning with improvements to the radiative transfer model and use of up-to-date HI Lyman α absorption optical depths (see McJunkin in posters) to better estimate disk structural parameters. Once improvements are implemented, we will investigate the possible presence of a molecular wind component in the observed H₂ fluorescence features by determining blue-shifted flux residuals in the data after best-fit model-to-data comparisons are complete.

Use of Molecular Modeling to Determine the Interaction and Competition of Gases within Coal for Carbon Dioxide Sequestration

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

Jeffrey D. Evanseck; Jeffry D. Madura

A 3-dimensional coal structural model for the Argonne Premium Coal Pocahontas No. 3 has been generated. The model was constructed based on the wealth of structural information available in the literature with the enhancement that the structural diversity within the structure was represented implicitly (for the first time) based on image analysis of HRTEM in combination with LDMS data. The complex and large structural model (>10,000 carbon atoms) will serve as a basis for examining the interaction of gases within this low volatile bituminous coal. Simulations are of interest to permit reasonable simulations of the host-guest interactions with regard tomore » carbon dioxide sequestration within coal and methane displacement from coal. The molecular structure will also prove useful in examining other coal related behavior such as solvent swelling, liquefaction and other properties. Molecular models of CO{sub 2} have been evaluated with water to analyze which classical molecular force-field parameters are the most reasonable to predict the interactions of CO{sub 2} with water. The comparison of the molecular force field models was for a single CO{sub 2}-H{sub 2}O complex and was compared against first principles quantum mechanical calculations. The interaction energies and the electrostatic interaction distances were used as criteria in the comparison. The ab initio calculations included Hartree-Fock, B3LYP, and Moeller-Plesset 2nd, 3rd, and 4th order perturbation theories with basis sets up to the aug-cc-pvtz basis set. The Steele model was the best literature model, when compared to the ab initio data, however, our new CO{sub 2} model reproduces the QM data significantly better than the Steele force-field model.« less

Quantifying the Effect of Polymer Blending through Molecular Modelling of Cyanurate Polymers

PubMed Central

Crawford, Alasdair O.; Hamerton, Ian; Cavalli, Gabriel; Howlin, Brendan J.

2012-01-01

Modification of polymer properties by blending is a common practice in the polymer industry. We report here a study of blends of cyanurate polymers by molecular modelling that shows that the final experimentally determined properties can be predicted from first principles modelling to a good degree of accuracy. There is always a compromise between simulation length, accuracy and speed of prediction. A comparison of simulation times shows that 125ps of molecular dynamics simulation at each temperature provides the optimum compromise for models of this size with current technology. This study opens up the possibility of computer aided design of polymer blends with desired physical and mechanical properties. PMID:22970230

Glioblastoma, a brief review of history, molecular genetics, animal models and novel therapeutic strategies.

PubMed

Agnihotri, Sameer; Burrell, Kelly E; Wolf, Amparo; Jalali, Sharzhad; Hawkins, Cynthia; Rutka, James T; Zadeh, Gelareh

2013-02-01

Glioblastoma (GBM) is the most common and lethal primary brain tumor. Over the past few years tremendous genomic and proteomic characterization along with robust animal models of GBM have provided invaluable data that show that "GBM", although histologically indistinguishable from one another, are comprised of molecularly heterogenous diseases. In addition, robust pre-clinical models and a better understanding of the core pathways disrupted in GBM are providing a renewed optimism for novel strategies targeting these devastating tumors. Here, we summarize a brief history of the disease, our current molecular knowledge, lessons from animal models and emerging concepts of angiogenesis, invasion, and metabolism in GBM that may lend themselves to therapeutic targeting.

Multi input single output model predictive control of non-linear bio-polymerization process

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

Arumugasamy, Senthil Kumar; Ahmad, Z.

This paper focuses on Multi Input Single Output (MISO) Model Predictive Control of bio-polymerization process in which mechanistic model is developed and linked with the feedforward neural network model to obtain a hybrid model (Mechanistic-FANN) of lipase-catalyzed ring-opening polymerization of ε-caprolactone (ε-CL) for Poly (ε-caprolactone) production. In this research, state space model was used, in which the input to the model were the reactor temperatures and reactor impeller speeds and the output were the molecular weight of polymer (M{sub n}) and polymer polydispersity index. State space model for MISO created using System identification tool box of Matlab™. This state spacemore » model is used in MISO MPC. Model predictive control (MPC) has been applied to predict the molecular weight of the biopolymer and consequently control the molecular weight of biopolymer. The result shows that MPC is able to track reference trajectory and give optimum movement of manipulated variable.« less

Origins Space Telescope: Tracing Dark Molecular Gas in the Milky Way

NASA Astrophysics Data System (ADS)

Narayanan, Desika; Li, Qi; Krumholz, Mark; Dave, Romeel; Origins Space Telescope Science and Technology Definition Team

2018-01-01

We present theoretical models for quantifying the fraction of CO-dark molecular gas in galaxies. To do this, we combine novel thermal, chemical, and radiative equilibrium calculations with high-resolution cosmological zoom galaxy formation models. We discuss how this dark molecular gas will be uncovered by the Origins Space Telescope, one of the four science and technology definition studies of NASA Headquarters for the 2020 Astronomy and Astrophysics Decadal survey.

Mirrored continuum and molecular scale simulations of the ignition of gamma phase RDX

NASA Astrophysics Data System (ADS)

Stewart, D. Scott; Chaudhuri, Santanu; Joshi, Kaushik; Lee, Kibaek

2017-01-01

We describe the ignition of an explosive crystal of gamma-phase RDX due to a thermal hot spot with reactive molecular dynamics (RMD), with first-principles trained, reactive force field based molecular potentials that represents an extremely complex reaction network. The RMD simulation is analyzed by sorting molecular product fragments into high and low molecular weight groups, to represent identifiable components that can be interpreted by a continuum model. A continuum model based on a Gibbs formulation has a single temperature and stress state for the mixture. The continuum simulation that mirrors the atomistic simulation allows us to study the atomistic simulation in the familiar physical chemistry framework and provides an essential, continuum/atomistic link.

Investigating the Fundamentals of Molecular Depth Profiling Using Strong-field Photoionization of Sputtered Neutrals

PubMed Central

Willingham, D.; Brenes, D. A.; Winograd, N.; Wucher, A.

2010-01-01

Molecular depth profiles of model organic thin films were performed using a 40 keV C60+ cluster ion source in concert with TOF-SIMS. Strong-field photoionization of intact neutral molecules sputtered by 40 keV C60+ primary ions was used to analyze changes in the chemical environment of the guanine thin films as a function of ion fluence. Direct comparison of the secondary ion and neutral components of the molecular depth profiles yields valuable information about chemical damage accumulation as well as changes in the molecular ionization probability. An analytical protocol based on the erosion dynamics model is developed and evaluated using guanine and trehalose molecular secondary ion signals with and without comparable laser photoionization data. PMID:26269660

Sulphur hexaflouride: low energy (e,2e) experiments and molecular three-body distorted wave theory

NASA Astrophysics Data System (ADS)

Nixon, Kate L.; Murray, Andrew J.; Chaluvadi, H.; Ning, C. G.; Colgan, James; Madison, Don H.

2016-10-01

Experimental and theoretical triple differential ionisation cross-sections (TDCSs) are presented for the highest occupied molecular orbital of sulphur hexafluoride. These measurements were performed in the low energy regime, with outgoing electron energies ranging from 5 to 40 eV in a coplanar geometry, and with energies of 10 and 20 eV in a perpendicular geometry. Complementary theoretical predictions of the TDCS were calculated using the molecular three-body distorted wave formalism. Calculations were performed using a proper average over molecular orientations as well as the orientation-averaged molecular orbital approximation. This more sophisticated model was found to be in closer agreement with the experimental data, however neither model accurately predicts the TDCS over all geometries and energies.

Possibility designing half-wave and full-wave molecular rectifiers by using single benzene molecule

NASA Astrophysics Data System (ADS)

Abbas, Mohammed A.; Hanoon, Falah H.; Al-Badry, Lafy F.

2018-02-01

This work focused on possibility designing half-wave and full-wave molecular rectifiers by using single and two benzene rings, respectively. The benzene rings were threaded by a magnetic flux that changes over time. The quantum interference effect was considered as the basic idea in the rectification action, the para and meta configurations were investigated. All the calculations are performed by using steady-state theoretical model, which is based on the time-dependent Hamiltonian model. The electrical conductance and the electric current are considered as DC output signals of half-wave and full-wave molecular rectifiers. The finding in this work opens up the exciting potential to use these molecular rectifiers in molecular electronics.

Molecular evolution tracks macroevolutionary transitions in Cetacea.

PubMed

McGowen, Michael R; Gatesy, John; Wildman, Derek E

2014-06-01

Cetacea (whales, dolphins, and porpoises) is a model group for investigating the molecular signature of macroevolutionary transitions. Recent research has begun to reveal the molecular underpinnings of the remarkable anatomical and behavioral transformation in this clade. This shift from terrestrial to aquatic environments is arguably the best-understood major morphological transition in vertebrate evolution. The ancestral body plan and physiology were extensively modified and, in many cases, these crucial changes are recorded in cetacean genomes. Recent studies have highlighted cetaceans as central to understanding adaptive molecular convergence and pseudogene formation. Here, we review current research in cetacean molecular evolution and the potential of Cetacea as a model for the study of other macroevolutionary transitions from a genomic perspective. Copyright © 2014 Elsevier Ltd. All rights reserved.

Molecular graph convolutions: moving beyond fingerprints

PubMed Central

Kearnes, Steven; McCloskey, Kevin; Berndl, Marc; Pande, Vijay; Riley, Patrick

2016-01-01

Molecular “fingerprints” encoding structural information are the workhorse of cheminformatics and machine learning in drug discovery applications. However, fingerprint representations necessarily emphasize particular aspects of the molecular structure while ignoring others, rather than allowing the model to make data-driven decisions. We describe molecular graph convolutions, a machine learning architecture for learning from undirected graphs, specifically small molecules. Graph convolutions use a simple encoding of the molecular graph—atoms, bonds, distances, etc.—which allows the model to take greater advantage of information in the graph structure. Although graph convolutions do not outperform all fingerprint-based methods, they (along with other graph-based methods) represent a new paradigm in ligand-based virtual screening with exciting opportunities for future improvement. PMID:27558503

Treatment of atomic and molecular line blanketing by opacity sampling. [atmospheric optics - stellar atmospheres

NASA Technical Reports Server (NTRS)

Johnson, H. R.; Krupp, B. M.

1975-01-01

An opacity sampling (OS) technique for treating the radiative opacity of large numbers of atomic and molecular lines in cool stellar atmospheres is presented. Tests were conducted and results show that the structure of atmospheric models is accurately fixed by the use of 1000 frequency points, and 500 frequency points is often adequate. The effects of atomic and molecular lines are separately studied. A test model computed by using the OS method agrees very well with a model having identical atmospheric parameters computed by the giant line (opacity distribution function) method.

Modeling the polydomain-monodomain transition of liquid crystal elastomers.

PubMed

Whitmer, Jonathan K; Roberts, Tyler F; Shekhar, Raj; Abbott, Nicholas L; de Pablo, Juan J

2013-02-01

We study the mechanism of the polydomain-monodomain transition in liquid crystalline elastomers at the molecular scale. A coarse-grained model is proposed in which mesogens are described as ellipsoidal particles. Molecular dynamics simulations are used to examine the transition from a polydomain state to a monodomain state in the presence of uniaxial strain. Our model demonstrates soft elasticity, similar to that exhibited by side-chain elastomers in the literature. By analyzing the growth dynamics of nematic domains during uniaxial extension, we provide direct evidence that at a molecular level the polydomain-monodomain transition proceeds through cluster rotation and domain growth.

Molecular motors that digest their track to rectify Brownian motion: processive movement of exonuclease enzymes.

PubMed

Xie, Ping

2009-09-16

A general model is presented for the processive movement of molecular motors such as λ-exonuclease, RecJ and exonuclease I that use digestion of a DNA track to rectify Brownian motion along this track. Using this model, the translocation dynamics of these molecular motors is studied. The sequence-dependent pausing of λ-exonuclease, which results from a site-specific high affinity DNA interaction, is also studied. The theoretical results are consistent with available experimental data. Moreover, the model is used to predict the lifetime distribution and force dependence of these paused states.

Thermal characterization assessment of rigid and flexible water models in a nanogap using molecular dynamics

NASA Astrophysics Data System (ADS)

Akıner, Tolga; Mason, Jeremy; Ertürk, Hakan

2017-11-01

The thermal properties of the TIP3P and TIP5P water models are investigated using equilibrium and non-equilibrium molecular dynamics techniques in the presence of solid surfaces. The performance of the non-equilibrium technique for rigid molecules is found to depend significantly on the distribution of atomic degrees of freedom. An improved approach to distribute atomic degrees of freedom is proposed for which the thermal conductivity of the TIP5P model agrees more closely with equilibrium molecular dynamics and experimental results than the existing state of the art.

Molecular dynamics simulations on discoidal HDL particles suggest a mechanism for rotation in the apo A-I belt model.

PubMed

Klon, Anthony E; Segrest, Jere P; Harvey, Stephen C

2002-12-06

Apolipoprotein A-I (apo A-I) is the major protein component of high-density lipoprotein (HDL) particles. Elevated levels of HDL in the bloodstream have been shown to correlate strongly with a reduced risk factor for atherosclerosis. Molecular dynamics simulations have been carried out on three separate model discoidal high-density lipoprotein particles (HDL) containing two monomers of apo A-I and 160 molecules of palmitoyloleoylphosphatidylcholine (POPC), to a time-scale of 1ns. The starting structures were on the basis of previously published molecular belt models of HDL consisting of the lipid-binding C-terminal domain (residues 44-243) wrapped around the circumference of a discoidal HDL particle. Subtle changes between two of the starting structures resulted in significantly different behavior during the course of the simulation. The results provide support for the hypothesis of Segrest et al. that helical registration in the molecular belt model of apo A-I is modulated by intermolecular salt bridges. In addition, we propose an explanation for the presence of proline punctuation in the molecular belt model, and for the presence of two 11-mer helical repeats interrupting the otherwise regular pattern of 22-mer helical repeats in the lipid-binding domain of apo A-I.

Structure-activity relationships for serotonin transporter and dopamine receptor selectivity.

PubMed

Agatonovic-Kustrin, Snezana; Davies, Paul; Turner, Joseph V

2009-05-01

Antipsychotic medications have a diverse pharmacology with affinity for serotonergic, dopaminergic, adrenergic, histaminergic and cholinergic receptors. Their clinical use now also includes the treatment of mood disorders, thought to be mediated by serotonergic receptor activity. The aim of our study was to characterise the molecular properties of antipsychotic agents, and to develop a model that would indicate molecular specificity for the dopamine (D(2)) receptor and the serotonin (5-HT) transporter. Back-propagation artificial neural networks (ANNs) were trained on a dataset of 47 ligands categorically assigned antidepressant or antipsychotic utility. The structure of each compound was encoded with 63 calculated molecular descriptors. ANN parameters including hidden neurons and input descriptors were optimised based on sensitivity analyses, with optimum models containing between four and 14 descriptors. Predicted binding preferences were in excellent agreement with clinical antipsychotic or antidepressant utility. Validated models were further tested by use of an external prediction set of five drugs with unknown mechanism of action. The SAR models developed revealed the importance of simple molecular characteristics for differential binding to the D(2) receptor and the 5-HT transporter. These included molecular size and shape, solubility parameters, hydrogen donating potential, electrostatic parameters, stereochemistry and presence of nitrogen. The developed models and techniques employed are expected to be useful in the rational design of future therapeutic agents.

Modelling the molecular mechanisms of aging

PubMed Central

Mc Auley, Mark T.; Guimera, Alvaro Martinez; Hodgson, David; Mcdonald, Neil; Mooney, Kathleen M.; Morgan, Amy E.

2017-01-01

The aging process is driven at the cellular level by random molecular damage that slowly accumulates with age. Although cells possess mechanisms to repair or remove damage, they are not 100% efficient and their efficiency declines with age. There are many molecular mechanisms involved and exogenous factors such as stress also contribute to the aging process. The complexity of the aging process has stimulated the use of computational modelling in order to increase our understanding of the system, test hypotheses and make testable predictions. As many different mechanisms are involved, a wide range of models have been developed. This paper gives an overview of the types of models that have been developed, the range of tools used, modelling standards and discusses many specific examples of models that have been grouped according to the main mechanisms that they address. We conclude by discussing the opportunities and challenges for future modelling in this field. PMID:28096317

Simple liquid models with corrected dielectric constants

PubMed Central

Fennell, Christopher J.; Li, Libo; Dill, Ken A.

2012-01-01

Molecular simulations often use explicit-solvent models. Sometimes explicit-solvent models can give inaccurate values for basic liquid properties, such as the density, heat capacity, and permittivity, as well as inaccurate values for molecular transfer free energies. Such errors have motivated the development of more complex solvents, such as polarizable models. We describe an alternative here. We give new fixed-charge models of solvents for molecular simulations – water, carbon tetrachloride, chloroform and dichloromethane. Normally, such solvent models are parameterized to agree with experimental values of the neat liquid density and enthalpy of vaporization. Here, in addition to those properties, our parameters are chosen to give the correct dielectric constant. We find that these new parameterizations also happen to give better values for other properties, such as the self-diffusion coefficient. We believe that parameterizing fixed-charge solvent models to fit experimental dielectric constants may provide better and more efficient ways to treat solvents in computer simulations. PMID:22397577

An Integrated Visualization and Basic Molecular Modeling Laboratory for First-Year Undergraduate Medicinal Chemistry

ERIC Educational Resources Information Center

Hayes, Joseph M.

2014-01-01

A 3D model visualization and basic molecular modeling laboratory suitable for first-year undergraduates studying introductory medicinal chemistry is presented. The 2 h practical is embedded within a series of lectures on drug design, target-drug interactions, enzymes, receptors, nucleic acids, and basic pharmacokinetics. Serving as a teaching aid…

Origami: A Versatile Modeling System for Visualising Chemical Structure and Exploring Molecular Function

ERIC Educational Resources Information Center

Davis, James; Leslie, Ray; Billington, Susan; Slater, Peter R.

2010-01-01

The use of "Origami" is presented as an accessible and transferable modeling system through which to convey the intricacies of molecular shape and highlight structure-function relationships. The implementation of origami has been found to be a versatile alternative to conventional ball-and-stick models, possessing the key advantages of being both…

Collective effects in models for interacting molecular motors and motor-microtubule mixtures

NASA Astrophysics Data System (ADS)

Menon, Gautam I.

2006-12-01

Three problems in the statistical mechanics of models for an assembly of molecular motors interacting with cytoskeletal filaments are reviewed. First, a description of the hydrodynamical behaviour of density-density correlations in fluctuating ratchet models for interacting molecular motors is outlined. Numerical evidence indicates that the scaling properties of dynamical behaviour in such models belong to the KPZ universality class. Second, the generalization of such models to include boundary injection and removal of motors is provided. In common with known results for the asymmetric exclusion processes, simulations indicate that such models exhibit sharp boundary driven phase transitions in the thermodynamic limit. In the third part of this paper, recent progress towards a continuum description of pattern formation in mixtures of motors and microtubules is described, and a non-equilibrium “phase-diagram” for such systems discussed.

Isochoric structural recovery in molecular glasses and its analog in colloidal glasses

NASA Astrophysics Data System (ADS)

Banik, Sourya; McKenna, Gregory B.

2018-06-01

Concentrated colloidal dispersions have been regarded as models for molecular glasses. One of the many ways to compare the behavior in these two different systems is by comparing the structural recovery or the physical aging behavior. However, recent investigations from our group to examine structural recovery in thermosensitive colloidal dispersions have shown contrasting results between the colloidal and the molecular glasses. The differences in the behaviors of the two systems have led us to pose this question: Is structural recovery behavior in colloidal glasses truly distinct from that of molecular glasses or is the conventional experimental condition (isobaric temperature-jumps) in determining the structural recovery in molecular glasses different from the experimental condition in the colloidal experiments (concentration- or volume fraction-jumps); i.e., are colloidal glasses inherently different from molecular glasses or not? To address the question, we resort to model calculations of structural recovery in a molecular glass under constant volume (isochoric) conditions following temperature only- and simultaneous volume- and temperature-jumps, which are closer to the volume fraction-jump conditions used in the thermosensitive-colloidal experiments. The current model predictions are then compared with the signatures of structural recovery under the conventional isobaric state in a molecular glass and with structural recovery behavior in colloidal glasses following volume fraction-jumps. We show that the results obtained from the experiments conducted by our group were contrasting to classical molecular glass behavior because the basis of our comparisons were incorrect (the histories were not analogous). The present calculations (with analogous histories) are qualitatively closer to the colloidal behavior. The signatures of "intrinsic isotherms" and "asymmetry of approach" in the current isochoric model predictions are quite different from those in the classical isobaric conditions while the "memory" signatures remain essentially the same. While there are qualitative similarities between the current isochoric model predictions and results from colloidal glasses, it appears from the calculations that the origins of these are different. The isochoric histories in the molecular glasses have compensating effects of pressure and departure from equilibrium which determines the structure dependence on mobility of the molecules. On the other hand, in the colloids it simply appears that the volume fraction-jump conditions simply do not exhibit such structure mobility dependence. The determining interplay of thermodynamic phase variables in colloidal and molecular systems might be very different or at least their correlations are yet to be ascertained. This topic requires further investigation to bring the similarities and differences between molecular and colloidal glass formers into fuller clarity.

Molecular theory of smectic ordering in liquid crystals with nanoscale segregation of different molecular fragments

NASA Astrophysics Data System (ADS)

Gorkunov, M. V.; Osipov, M. A.; Kapernaum, N.; Nonnenmacher, D.; Giesselmann, F.

2011-11-01

A molecular statistical theory of the smectic A phase is developed taking into account specific interactions between different molecular fragments which enables one to describe different microscopic scenario of the transition into the smectic phase. The effects of nanoscale segregation are described using molecular models with different combinations of attractive and repulsive sites. These models have been used to calculate numerically coefficients in the mean filed potential as functions of molecular model parameters and the period of the smectic structure. The same coefficients are calculated also for a conventional smectic with standard Gay-Berne interaction potential which does not promote the segregation. The free energy is minimized numerically to calculate the order parameters of the smectic A phases and to study the nature of the smectic transition in both systems. It has been found that in conventional materials the smectic order can be stabilized only when the orientational order is sufficiently high, In contrast, in materials with nanosegregation the smectic order develops mainly in the form of the orientational-translational wave while the nematic order parameter remains relatively small. Microscopic mechanisms of smectic ordering in both systems are discussed in detail, and the results for smectic order parameters are compared with experimental data for materials of various molecular structure.

Modeling of diatomic molecule using the Morse potential and the Verlet algorithm

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

Fidiani, Elok

Performing molecular modeling usually uses special software for Molecular Dynamics (MD) such as: GROMACS, NAMD, JMOL etc. Molecular dynamics is a computational method to calculate the time dependent behavior of a molecular system. In this work, MATLAB was used as numerical method for a simple modeling of some diatomic molecules: HCl, H{sub 2} and O{sub 2}. MATLAB is a matrix based numerical software, in order to do numerical analysis, all the functions and equations describing properties of atoms and molecules must be developed manually in MATLAB. In this work, a Morse potential was generated to describe the bond interaction betweenmore » the two atoms. In order to analyze the simultaneous motion of molecules, the Verlet Algorithm derived from Newton’s Equations of Motion (classical mechanics) was operated. Both the Morse potential and the Verlet algorithm were integrated using MATLAB to derive physical properties and the trajectory of the molecules. The data computed by MATLAB is always in the form of a matrix. To visualize it, Visualized Molecular Dynamics (VMD) was performed. Such method is useful for development and testing some types of interaction on a molecular scale. Besides, this can be very helpful for describing some basic principles of molecular interaction for educational purposes.« less

Of truth and pathways: chasing bits of information through myriads of articles.

PubMed

Krauthammer, Michael; Kra, Pauline; Iossifov, Ivan; Gomez, Shawn M; Hripcsak, George; Hatzivassiloglou, Vasileios; Friedman, Carol; Rzhetsky, Andrey

2002-01-01

Knowledge on interactions between molecules in living cells is indispensable for theoretical analysis and practical applications in modern genomics and molecular biology. Building such networks relies on the assumption that the correct molecular interactions are known or can be identified by reading a few research articles. However, this assumption does not necessarily hold, as truth is rather an emerging property based on many potentially conflicting facts. This paper explores the processes of knowledge generation and publishing in the molecular biology literature using modelling and analysis of real molecular interaction data. The data analysed in this article were automatically extracted from 50000 research articles in molecular biology using a computer system called GeneWays containing a natural language processing module. The paper indicates that truthfulness of statements is associated in the minds of scientists with the relative importance (connectedness) of substances under study, revealing a potential selection bias in the reporting of research results. Aiming at understanding the statistical properties of the life cycle of biological facts reported in research articles, we formulate a stochastic model describing generation and propagation of knowledge about molecular interactions through scientific publications. We hope that in the future such a model can be useful for automatically producing consensus views of molecular interaction data.

Star formation in evolving molecular clouds

NASA Astrophysics Data System (ADS)

Völschow, M.; Banerjee, R.; Körtgen, B.

2017-09-01

Molecular clouds are the principle stellar nurseries of our universe; they thus remain a focus of both observational and theoretical studies. From observations, some of the key properties of molecular clouds are well known but many questions regarding their evolution and star formation activity remain open. While numerical simulations feature a large number and complexity of involved physical processes, this plethora of effects may hide the fundamentals that determine the evolution of molecular clouds and enable the formation of stars. Purely analytical models, on the other hand, tend to suffer from rough approximations or a lack of completeness, limiting their predictive power. In this paper, we present a model that incorporates central concepts of astrophysics as well as reliable results from recent simulations of molecular clouds and their evolutionary paths. Based on that, we construct a self-consistent semi-analytical framework that describes the formation, evolution, and star formation activity of molecular clouds, including a number of feedback effects to account for the complex processes inside those objects. The final equation system is solved numerically but at much lower computational expense than, for example, hydrodynamical descriptions of comparable systems. The model presented in this paper agrees well with a broad range of observational results, showing that molecular cloud evolution can be understood as an interplay between accretion, global collapse, star formation, and stellar feedback.

Quantitative structure-property relationships for octanol-water partition coefficients of polybrominated diphenyl ethers.

PubMed

Li, Linnan; Xie, Shaodong; Cai, Hao; Bai, Xuetao; Xue, Zhao

2008-08-01

Theoretical molecular descriptors were tested against logK(OW) values for polybrominated diphenyl ethers (PBDEs) using the Partial Least-Squares Regression method which can be used to analyze data with many variables and few observations. A quantitative structure-property relationship (QSPR) model was successfully developed with a high cross-validated value (Q(cum)(2)) of 0.961, indicating a good predictive ability and stability of the model. The predictive power of the QSPR model was further cross-validated. The values of logK(OW) for PBDEs are mainly governed by molecular surface area, energy of the lowest unoccupied molecular orbital and the net atomic charges on the oxygen atom. All these descriptors have been discussed to interpret the partitioning mechanism of PBDE chemicals. The bulk property of the molecules represented by molecular surface area is the leading factor, and K(OW) values increase with the increase of molecular surface area. Higher energy of the lowest unoccupied molecular orbital and higher net atomic charge on the oxygen atom of PBDEs result in smaller K(OW). The energy of the lowest unoccupied molecular orbital and the net atomic charge on PBDEs oxygen also play important roles in affecting the partition of PBDEs between octanol and water by influencing the interactions between PBDEs and solvent molecules.

Coupling discrete and continuum concentration particle models for multiscale and hybrid molecular-continuum simulations

NASA Astrophysics Data System (ADS)

Petsev, Nikolai D.; Leal, L. Gary; Shell, M. Scott

2017-12-01

Hybrid molecular-continuum simulation techniques afford a number of advantages for problems in the rapidly burgeoning area of nanoscale engineering and technology, though they are typically quite complex to implement and limited to single-component fluid systems. We describe an approach for modeling multicomponent hydrodynamic problems spanning multiple length scales when using particle-based descriptions for both the finely resolved (e.g., molecular dynamics) and coarse-grained (e.g., continuum) subregions within an overall simulation domain. This technique is based on the multiscale methodology previously developed for mesoscale binary fluids [N. D. Petsev, L. G. Leal, and M. S. Shell, J. Chem. Phys. 144, 084115 (2016)], simulated using a particle-based continuum method known as smoothed dissipative particle dynamics. An important application of this approach is the ability to perform coupled molecular dynamics (MD) and continuum modeling of molecularly miscible binary mixtures. In order to validate this technique, we investigate multicomponent hybrid MD-continuum simulations at equilibrium, as well as non-equilibrium cases featuring concentration gradients.

The Physiological Molecular Shape of Spectrin: A Compact Supercoil Resembling a Chinese Finger Trap.

PubMed

Brown, Jeffrey W; Bullitt, Esther; Sriswasdi, Sira; Harper, Sandra; Speicher, David W; McKnight, C James

2015-06-01

The primary, secondary, and tertiary structures of spectrin are reasonably well defined, but the structural basis for the known dramatic molecular shape change, whereby the molecular length can increase three-fold, is not understood. In this study, we combine previously reported biochemical and high-resolution crystallographic data with structural mass spectroscopy and electron microscopic data to derive a detailed, experimentally-supported quaternary structure of the spectrin heterotetramer. In addition to explaining spectrin's physiological resting length of ~55-65 nm, our model provides a mechanism by which spectrin is able to undergo a seamless three-fold extension while remaining a linear filament, an experimentally observed property. According to the proposed model, spectrin's quaternary structure and mechanism of extension is similar to a Chinese Finger Trap: at shorter molecular lengths spectrin is a hollow cylinder that extends by increasing the pitch of each spectrin repeat, which decreases the internal diameter. We validated our model with electron microscopy, which demonstrated that, as predicted, spectrin is hollow at its biological resting length of ~55-65 nm. The model is further supported by zero-length chemical crosslink data indicative of an approximately 90 degree bend between adjacent spectrin repeats. The domain-domain interactions in our model are entirely consistent with those present in the prototypical linear antiparallel heterotetramer as well as recently reported inter-strand chemical crosslinks. The model is consistent with all known physical properties of spectrin, and upon full extension our Chinese Finger Trap Model reduces to the ~180-200 nm molecular model currently in common use.

Study of homogeneous bubble nucleation in liquid carbon dioxide by a hybrid approach combining molecular dynamics simulation and density gradient theory

NASA Astrophysics Data System (ADS)

Langenbach, K.; Heilig, M.; Horsch, M.; Hasse, H.

2018-03-01

A new method for predicting homogeneous bubble nucleation rates of pure compounds from vapor-liquid equilibrium (VLE) data is presented. It combines molecular dynamics simulation on the one side with density gradient theory using an equation of state (EOS) on the other. The new method is applied here to predict bubble nucleation rates in metastable liquid carbon dioxide (CO2). The molecular model of CO2 is taken from previous work of our group. PC-SAFT is used as an EOS. The consistency between the molecular model and the EOS is achieved by adjusting the PC-SAFT parameters to VLE data obtained from the molecular model. The influence parameter of density gradient theory is fitted to the surface tension of the molecular model. Massively parallel molecular dynamics simulations are performed close to the spinodal to compute bubble nucleation rates. From these simulations, the kinetic prefactor of the hybrid nucleation theory is estimated, whereas the nucleation barrier is calculated from density gradient theory. This enables the extrapolation of molecular simulation data to the whole metastable range including technically relevant densities. The results are tested against available experimental data and found to be in good agreement. The new method does not suffer from typical deficiencies of classical nucleation theory concerning the thermodynamic barrier at the spinodal and the bubble size dependence of surface tension, which is typically neglected in classical nucleation theory. In addition, the density in the center of critical bubbles and their surface tension is determined as a function of their radius. The usual linear Tolman correction to the capillarity approximation is found to be invalid.

Study of homogeneous bubble nucleation in liquid carbon dioxide by a hybrid approach combining molecular dynamics simulation and density gradient theory.

PubMed

Langenbach, K; Heilig, M; Horsch, M; Hasse, H

2018-03-28

A new method for predicting homogeneous bubble nucleation rates of pure compounds from vapor-liquid equilibrium (VLE) data is presented. It combines molecular dynamics simulation on the one side with density gradient theory using an equation of state (EOS) on the other. The new method is applied here to predict bubble nucleation rates in metastable liquid carbon dioxide (CO 2 ). The molecular model of CO 2 is taken from previous work of our group. PC-SAFT is used as an EOS. The consistency between the molecular model and the EOS is achieved by adjusting the PC-SAFT parameters to VLE data obtained from the molecular model. The influence parameter of density gradient theory is fitted to the surface tension of the molecular model. Massively parallel molecular dynamics simulations are performed close to the spinodal to compute bubble nucleation rates. From these simulations, the kinetic prefactor of the hybrid nucleation theory is estimated, whereas the nucleation barrier is calculated from density gradient theory. This enables the extrapolation of molecular simulation data to the whole metastable range including technically relevant densities. The results are tested against available experimental data and found to be in good agreement. The new method does not suffer from typical deficiencies of classical nucleation theory concerning the thermodynamic barrier at the spinodal and the bubble size dependence of surface tension, which is typically neglected in classical nucleation theory. In addition, the density in the center of critical bubbles and their surface tension is determined as a function of their radius. The usual linear Tolman correction to the capillarity approximation is found to be invalid.

Student Misapplication of a Gas-Like Model to Explain Particle Movement in Heated Solids: Implications for Curriculum and Instruction towards Students' Creation and Revision of Accurate Explanatory Models

ERIC Educational Resources Information Center

Bouwma-Gearhart, Jana; Stewart, James; Brown, Keffrelyn

2009-01-01

Understanding the particulate nature of matter (PNM) is vital for participating in many areas of science. We assessed 11 students' atomic/molecular-level explanations of real-world phenomena after their participation in a modelling-based PNM unit. All 11 students offered a scientifically acceptable model regarding atomic/molecular behaviour in…

A study of some non-equilibrium driven models and their contribution to the understanding of molecular motors

NASA Astrophysics Data System (ADS)

Mazilu, Irina; Gonzalez, Joshua

2008-03-01

From the point of view of a physicist, a bio-molecular motor represents an interesting non-equilibrium system and it is directly amenable to an analysis using standard methods of non-equilibrium statistical physics. We conduct a rigorous Monte Carlo study of three different driven lattice gas models that retain the basic behavior of three types of cytoskeletal molecular motors. Our models incorporate novel features such as realistic dynamics rules and complex motor-motor interactions. We are interested to have a deeper understanding of how various parameters influence the macroscopic behavior of these systems, what is the density profile and if the system undergoes a phase transition. On the analytical front, we computed the steady-state probability distributions exactly for the one of the models using the matrix method that was established in 1993 by B. Derrida et al. We also explored the possibilities offered by the ``Bethe ansatz'' method by mapping some well studied spin models into asymmetric simple exclusion models (already analyzed using computer simulations), and to use the results obtained for the spin models in finding an exact solution for our problem. We have exhaustive computational studies of the kinesin and dynein molecular motor models that prove to be very useful in checking our analytical work.

Institute for Molecular Medicine Research Program

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

Phelps, Michael E

2012-12-14

The objectives of the project are the development of new Positron Emission Tomography (PET) imaging instrumentation, chemistry technology platforms and new molecular imaging probes to examine the transformations from normal cellular and biological processes to those of disease in pre-clinical animal models. These technology platforms and imaging probes provide the means to: 1. Study the biology of disease using pre-clinical mouse models and cells. 2. Develop molecular imaging probes for imaging assays of proteins in pre-clinical models. 3. Develop imaging assays in pre-clinical models to provide to other scientists the means to guide and improve the processes for discovering newmore » drugs. 4. Develop imaging assays in pre-clinical models for others to use in judging the impact of drugs on the biology of disease.« less

A fragmentation and reassembly method for ab initio phasing.

PubMed

Shrestha, Rojan; Zhang, Kam Y J

2015-02-01

Ab initio phasing with de novo models has become a viable approach for structural solution from protein crystallographic diffraction data. This approach takes advantage of the known protein sequence information, predicts de novo models and uses them for structure determination by molecular replacement. However, even the current state-of-the-art de novo modelling method has a limit as to the accuracy of the model predicted, which is sometimes insufficient to be used as a template for successful molecular replacement. A fragment-assembly phasing method has been developed that starts from an ensemble of low-accuracy de novo models, disassembles them into fragments, places them independently in the crystallographic unit cell by molecular replacement and then reassembles them into a whole structure that can provide sufficient phase information to enable complete structure determination by automated model building. Tests on ten protein targets showed that the method could solve structures for eight of these targets, although the predicted de novo models cannot be used as templates for successful molecular replacement since the best model for each target is on average more than 4.0 Å away from the native structure. The method has extended the applicability of the ab initio phasing by de novo models approach. The method can be used to solve structures when the best de novo models are still of low accuracy.

Water models based on a single potential energy surface and different molecular degrees of freedom

NASA Astrophysics Data System (ADS)

Saint-Martin, Humberto; Hernández-Cobos, Jorge; Ortega-Blake, Iván

2005-06-01

Up to now it has not been possible to neatly assess whether a deficient performance of a model is due to poor parametrization of the force field or the lack of inclusion of enough molecular properties. This work compares several molecular models in the framework of the same force field, which was designed to include many-body nonadditive effects: (a) a polarizable and flexible molecule with constraints that account for the quantal nature of the vibration [B. Hess, H. Saint-Martin, and H. J. C. Berendsen, J. Chem. Phys. 116, 9602 (2002), H. Saint-Martin, B. Hess, and H. J. C. Berendsen, J. Chem. Phys. 120, 11133 (2004)], (b) a polarizable and classically flexible molecule [H. Saint-Martin, J. Hernández-Cobos, M. I. Bernal-Uruchurtu, I. Ortega-Blake, and H. J. C. Berendsen, J. Chem. Phys. 113, 10899 (2000)], (c) a polarizable and rigid molecule, and finally (d) a nonpolarizable and rigid molecule. The goal is to determine how significant the different molecular properties are. The results indicate that all factors—nonadditivity, polarizability, and intramolecular flexibility—are important. Still, approximations can be made in order to diminish the computational cost of the simulations with a small decrease in the accuracy of the predictions, provided that those approximations are counterbalanced by the proper inclusion of an effective molecular property, that is, an average molecular geometry or an average dipole. Hence instead of building an effective force field by parametrizing it in order to reproduce the properties of a specific phase, a building approach is proposed that is based on adequately restricting the molecular flexibility and/or polarizability of a model potential fitted to unimolecular properties, pair interactions, and many-body nonadditive contributions. In this manner, the same parental model can be used to simulate the same substance under a wide range of thermodynamic conditions. An additional advantage of this approach is that, as the force field improves by the quality of the molecular calculations, all levels of modeling can be improved.

Molecular Modeling of Thermodynamic and Transport Properties for CO 2 and Aqueous Brines

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

Jiang, Hao; Economou, Ioannis G.; Panagiotopoulos, Athanassios Z.

Molecular simulation techniques using classical force-fields occupy the space between ab initio quantum mechanical methods and phenomenological correlations. In particular, Monte Carlo and molecular dynamics algorithms can be used to provide quantitative predictions of thermodynamic and transport properties of fluids relevant for geologic carbon sequestration at conditions for which experimental data are uncertain or not available. These methods can cover time and length scales far exceeding those of quantum chemical methods, while maintaining transferability and predictive power lacking from phenomenological correlations. The accuracy of predictions depends sensitively on the quality of the molecular models used. Many existing fixed-point-charge models formore » water and aqueous mixtures fail to represent accurately these fluid properties, especially when descriptions covering broad ranges of thermodynamic conditions are needed. Recent work on development of accurate models for water, CO 2, and dissolved salts, as well as their mixtures, is summarized in this Account. Polarizable models that can respond to the different dielectric environments in aqueous versus nonaqueous phases are necessary for predictions of properties over extended ranges of temperatures and pressures. Phase compositions and densities, activity coefficients of the dissolved salts, interfacial tensions, viscosities and diffusivities can be obtained in near-quantitative agreement to available experimental data, using relatively modest computational resources. In some cases, for example, for the composition of the CO 2-rich phase in coexistence with an aqueous phase, recent results from molecular simulations have helped discriminate among conflicting experimental data sets. The sensitivity of properties on the quality of the intermolecular interaction model varies significantly. Properties such as the phase compositions or electrolyte activity coefficients are much more sensitive than phase densities, viscosities, or component diffusivities. Strong confinement effects on physical properties in nanoscale media can also be directly obtained from molecular simulations. Future work on molecular modeling for CO 2 and aqueous brines is likely to be focused on more systematic generation of interaction models by utilizing quantum chemical as well as direct experimental measurements. New ion models need to be developed for use with the current generation of polarizable water models, including ion–ion interactions that will allow for accurate description of dense, mixed brines. Methods will need to be devised that go beyond the use of effective potentials for incorporation of quantum effects known to be important for water, and reactive force fields developed that can handle bond creation and breaking in systems with carbonate and silicate minerals. Lastly, another area of potential future work is the integration of molecular simulation methods in multiscale models for the chemical reactions leading to mineral dissolution and flow within the porous media in underground formations.« less

Molecular Modeling of Thermodynamic and Transport Properties for CO2 and Aqueous Brines.

PubMed

Jiang, Hao; Economou, Ioannis G; Panagiotopoulos, Athanassios Z

2017-04-18

Molecular simulation techniques using classical force-fields occupy the space between ab initio quantum mechanical methods and phenomenological correlations. In particular, Monte Carlo and molecular dynamics algorithms can be used to provide quantitative predictions of thermodynamic and transport properties of fluids relevant for geologic carbon sequestration at conditions for which experimental data are uncertain or not available. These methods can cover time and length scales far exceeding those of quantum chemical methods, while maintaining transferability and predictive power lacking from phenomenological correlations. The accuracy of predictions depends sensitively on the quality of the molecular models used. Many existing fixed-point-charge models for water and aqueous mixtures fail to represent accurately these fluid properties, especially when descriptions covering broad ranges of thermodynamic conditions are needed. Recent work on development of accurate models for water, CO 2 , and dissolved salts, as well as their mixtures, is summarized in this Account. Polarizable models that can respond to the different dielectric environments in aqueous versus nonaqueous phases are necessary for predictions of properties over extended ranges of temperatures and pressures. Phase compositions and densities, activity coefficients of the dissolved salts, interfacial tensions, viscosities and diffusivities can be obtained in near-quantitative agreement to available experimental data, using relatively modest computational resources. In some cases, for example, for the composition of the CO 2 -rich phase in coexistence with an aqueous phase, recent results from molecular simulations have helped discriminate among conflicting experimental data sets. The sensitivity of properties on the quality of the intermolecular interaction model varies significantly. Properties such as the phase compositions or electrolyte activity coefficients are much more sensitive than phase densities, viscosities, or component diffusivities. Strong confinement effects on physical properties in nanoscale media can also be directly obtained from molecular simulations. Future work on molecular modeling for CO 2 and aqueous brines is likely to be focused on more systematic generation of interaction models by utilizing quantum chemical as well as direct experimental measurements. New ion models need to be developed for use with the current generation of polarizable water models, including ion-ion interactions that will allow for accurate description of dense, mixed brines. Methods will need to be devised that go beyond the use of effective potentials for incorporation of quantum effects known to be important for water, and reactive force fields developed that can handle bond creation and breaking in systems with carbonate and silicate minerals. Another area of potential future work is the integration of molecular simulation methods in multiscale models for the chemical reactions leading to mineral dissolution and flow within the porous media in underground formations.

Molecular Modeling of Thermodynamic and Transport Properties for CO 2 and Aqueous Brines

DOE PAGES

Jiang, Hao; Economou, Ioannis G.; Panagiotopoulos, Athanassios Z.

2017-02-24

Molecular simulation techniques using classical force-fields occupy the space between ab initio quantum mechanical methods and phenomenological correlations. In particular, Monte Carlo and molecular dynamics algorithms can be used to provide quantitative predictions of thermodynamic and transport properties of fluids relevant for geologic carbon sequestration at conditions for which experimental data are uncertain or not available. These methods can cover time and length scales far exceeding those of quantum chemical methods, while maintaining transferability and predictive power lacking from phenomenological correlations. The accuracy of predictions depends sensitively on the quality of the molecular models used. Many existing fixed-point-charge models formore » water and aqueous mixtures fail to represent accurately these fluid properties, especially when descriptions covering broad ranges of thermodynamic conditions are needed. Recent work on development of accurate models for water, CO 2, and dissolved salts, as well as their mixtures, is summarized in this Account. Polarizable models that can respond to the different dielectric environments in aqueous versus nonaqueous phases are necessary for predictions of properties over extended ranges of temperatures and pressures. Phase compositions and densities, activity coefficients of the dissolved salts, interfacial tensions, viscosities and diffusivities can be obtained in near-quantitative agreement to available experimental data, using relatively modest computational resources. In some cases, for example, for the composition of the CO 2-rich phase in coexistence with an aqueous phase, recent results from molecular simulations have helped discriminate among conflicting experimental data sets. The sensitivity of properties on the quality of the intermolecular interaction model varies significantly. Properties such as the phase compositions or electrolyte activity coefficients are much more sensitive than phase densities, viscosities, or component diffusivities. Strong confinement effects on physical properties in nanoscale media can also be directly obtained from molecular simulations. Future work on molecular modeling for CO 2 and aqueous brines is likely to be focused on more systematic generation of interaction models by utilizing quantum chemical as well as direct experimental measurements. New ion models need to be developed for use with the current generation of polarizable water models, including ion–ion interactions that will allow for accurate description of dense, mixed brines. Methods will need to be devised that go beyond the use of effective potentials for incorporation of quantum effects known to be important for water, and reactive force fields developed that can handle bond creation and breaking in systems with carbonate and silicate minerals. Lastly, another area of potential future work is the integration of molecular simulation methods in multiscale models for the chemical reactions leading to mineral dissolution and flow within the porous media in underground formations.« less

Computational Modeling of Airway and Pulmonary Vascular Structure and Function: Development of a “Lung Physiome”

PubMed Central

Tawhai, M. H.; Clark, A. R.; Donovan, G. M.; Burrowes, K. S.

2011-01-01

Computational models of lung structure and function necessarily span multiple spatial and temporal scales, i.e., dynamic molecular interactions give rise to whole organ function, and the link between these scales cannot be fully understood if only molecular or organ-level function is considered. Here, we review progress in constructing multiscale finite element models of lung structure and function that are aimed at providing a computational framework for bridging the spatial scales from molecular to whole organ. These include structural models of the intact lung, embedded models of the pulmonary airways that couple to model lung tissue, and models of the pulmonary vasculature that account for distinct structural differences at the extra- and intra-acinar levels. Biophysically based functional models for tissue deformation, pulmonary blood flow, and airway bronchoconstriction are also described. The development of these advanced multiscale models has led to a better understanding of complex physiological mechanisms that govern regional lung perfusion and emergent heterogeneity during bronchoconstriction. PMID:22011236

The display of molecular models with the Ames Interactive Modeling System (AIMS)

NASA Technical Reports Server (NTRS)

Egan, J. T.; Hart, J.; Burt, S. K.; Macelroy, R. D.

1982-01-01

A visualization of molecular models can lead to a clearer understanding of the models. Sophisticated graphics devices supported by minicomputers make it possible for the chemist to interact with the display of a very large model, altering its structure. In addition to user interaction, the need arises also for other ways of displaying information. These include the production of viewgraphs, film presentation, as well as publication quality prints of various models. To satisfy these needs, the display capability of the Ames Interactive Modeling System (AIMS) has been enhanced to provide a wide range of graphics and plotting capabilities. Attention is given to an overview of the AIMS system, graphics hardware used by the AIMS display subsystem, a comparison of graphics hardware, the representation of molecular models, graphics software used by the AIMS display subsystem, the display of a model obtained from data stored in molecule data base, a graphics feature for obtaining single frame permanent copy displays, and a feature for producing multiple frame displays.

MODELING THE INTERACTION OF AGROCHEMICALS WITH ENVIRONMENTAL SURFACES: PESTICIDES ON RUTILE AND ORGANO-RUTILE SURFACES

EPA Science Inventory

Non-bonded interactions between model pesticides and organo-mineral surfaces have been studied using molecular mechanical conformational calculations and molecular dynamics simulations. The minimum energy conformations and relative binding energies for the interaction of atrazine...

Mobile modeling in the molecular sciences

EPA Science Inventory

The art of modeling in the molecular sciences is highly dependent on both the available computational technology, underlying data, and ability to collaborate. With the ever increasing market share of mobile devices, it is assumed by many that tablets will overtake laptops as the...

Knowledge environments representing molecular entities for the virtual physiological human.

PubMed

Hofmann-Apitius, Martin; Fluck, Juliane; Furlong, Laura; Fornes, Oriol; Kolárik, Corinna; Hanser, Susanne; Boeker, Martin; Schulz, Stefan; Sanz, Ferran; Klinger, Roman; Mevissen, Theo; Gattermayer, Tobias; Oliva, Baldo; Friedrich, Christoph M

2008-09-13

In essence, the virtual physiological human (VPH) is a multiscale representation of human physiology spanning from the molecular level via cellular processes and multicellular organization of tissues to complex organ function. The different scales of the VPH deal with different entities, relationships and processes, and in consequence the models used to describe and simulate biological functions vary significantly. Here, we describe methods and strategies to generate knowledge environments representing molecular entities that can be used for modelling the molecular scale of the VPH. Our strategy to generate knowledge environments representing molecular entities is based on the combination of information extraction from scientific text and the integration of information from biomolecular databases. We introduce @neuLink, a first prototype of an automatically generated, disease-specific knowledge environment combining biomolecular, chemical, genetic and medical information. Finally, we provide a perspective for the future implementation and use of knowledge environments representing molecular entities for the VPH.

Histories of molecules: Reconciling the past.

PubMed

O'Malley, Maureen A

2016-02-01

Molecular data and methods have become centrally important to evolutionary analysis, largely because they have enabled global phylogenetic reconstructions of the relationships between organisms in the tree of life. Often, however, molecular stories conflict dramatically with morphology-based histories of lineages. The evolutionary origin of animal groups provides one such case. In other instances, different molecular analyses have so far proved irreconcilable. The ancient and major divergence of eukaryotes from prokaryotic ancestors is an example of this sort of problem. Efforts to overcome these conflicts highlight the role models play in phylogenetic reconstruction. One crucial model is the molecular clock; another is that of 'simple-to-complex' modification. I will examine animal and eukaryote evolution against a backdrop of increasing methodological sophistication in molecular phylogeny, and conclude with some reflections on the nature of historical science in the molecular era of phylogeny. Copyright © 2015 Elsevier Ltd. All rights reserved.

A new predictive model for the bioconcentration factors of polychlorinated biphenyls (PCBs) based on the molecular electronegativity distance vector (MEDV).

PubMed

Qin, Li-Tang; Liu, Shu-Shen; Liu, Hai-Ling; Ge, Hui-Lin

2008-02-01

Polychlorinated biphenyls (PCBs) are some of the most prevalent pollutants in the total environment and receive more and more concerns as a group of ubiquitous potential persistent organic pollutants. Using the variable selection and modeling based on prediction (VSMP), the molecular electronegativity distance vector (MEDV) derived directly from the molecular topological structures was employed to develop a linear model (MI) between the bioconcentration factors (BCF) and two MEDV descriptors of 58 PCBs. The MI model showed a good estimation ability with a correlation coefficient (r) of 0.9605 and a high stability with a leave-one-out cross-validation correlation coefficient (q) of 0.9564. The MEDV-base model (MI) is easier to use than the splinoid poset method reported by Ivanciuc et al. [Ivanciuc, T., Ivanciuc, O., Klein, D.J., 2006. Modeling the bioconcentration factors and bioaccumulation factors of polychlorinated biphenyls with posetic quatitative super-structure/activity relationships (QSSAR). Mol. Divers. 10, 133-145] and gives a better statistics than molecular connectivity index (MCI)-base model developed by Hu et al. [Hu, H.Y., Xu, F.L., Li, B.G., Cao, J., Dawson, R., Tao, S., 2005. Prediction of the bioconcentration factor of PCBs in fish using the molecular connectivity index and fragment constant models. Water Environ. Res. 77, 87-97]. Main structural factors influencing the BCF of PCBs are the substructures expressed by two atomic groups >C= and -CH=. 58 PCBs were divided into an "odd set" and "even set" in order to ensure the predicted potential of the MI for the external samples. It was shown that three models, MI, MO for "odd set", and ME for "even set", can be used to predict the BCF of remaining 152 PCBs in which the experimental BCFs are not available.

Variational Koopman models: Slow collective variables and molecular kinetics from short off-equilibrium simulations

NASA Astrophysics Data System (ADS)

Wu, Hao; Nüske, Feliks; Paul, Fabian; Klus, Stefan; Koltai, Péter; Noé, Frank

2017-04-01

Markov state models (MSMs) and master equation models are popular approaches to approximate molecular kinetics, equilibria, metastable states, and reaction coordinates in terms of a state space discretization usually obtained by clustering. Recently, a powerful generalization of MSMs has been introduced, the variational approach conformation dynamics/molecular kinetics (VAC) and its special case the time-lagged independent component analysis (TICA), which allow us to approximate slow collective variables and molecular kinetics by linear combinations of smooth basis functions or order parameters. While it is known how to estimate MSMs from trajectories whose starting points are not sampled from an equilibrium ensemble, this has not yet been the case for TICA and the VAC. Previous estimates from short trajectories have been strongly biased and thus not variationally optimal. Here, we employ the Koopman operator theory and the ideas from dynamic mode decomposition to extend the VAC and TICA to non-equilibrium data. The main insight is that the VAC and TICA provide a coefficient matrix that we call Koopman model, as it approximates the underlying dynamical (Koopman) operator in conjunction with the basis set used. This Koopman model can be used to compute a stationary vector to reweight the data to equilibrium. From such a Koopman-reweighted sample, equilibrium expectation values and variationally optimal reversible Koopman models can be constructed even with short simulations. The Koopman model can be used to propagate densities, and its eigenvalue decomposition provides estimates of relaxation time scales and slow collective variables for dimension reduction. Koopman models are generalizations of Markov state models, TICA, and the linear VAC and allow molecular kinetics to be described without a cluster discretization.

Impact-parameter dependence of the energy loss of fast molecular clusters in hydrogen

NASA Astrophysics Data System (ADS)

Fadanelli, R. C.; Grande, P. L.; Schiwietz, G.

2008-03-01

The electronic energy loss of molecular clusters as a function of impact parameter is far less understood than atomic energy losses. For instance, there are no analytical expressions for the energy loss as a function of impact parameter for cluster ions. In this work, we describe two procedures to evaluate the combined energy loss of molecules: Ab initio calculations within the semiclassical approximation and the coupled-channels method using atomic orbitals; and simplified models for the electronic cluster energy loss as a function of the impact parameter, namely the molecular perturbative convolution approximation (MPCA, an extension of the corresponding atomic model PCA) and the molecular unitary convolution approximation (MUCA, a molecular extension of the previous unitary convolution approximation UCA). In this work, an improved ansatz for MPCA is proposed, extending its validity for very compact clusters. For the simplified models, the physical inputs are the oscillators strengths of the target atoms and the target-electron density. The results from these models applied to an atomic hydrogen target yield remarkable agreement with their corresponding ab initio counterparts for different angles between cluster axis and velocity direction at specific energies of 150 and 300 keV/u.

Simple model of a coherent molecular photocell

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

Ernzerhof, Matthias, E-mail: Matthias.Ernzerhof@UMontreal.ca; Bélanger, Marc-André; Mayou, Didier

2016-04-07

Electron transport in molecular electronic devices is often dominated by a coherent mechanism in which the wave function extends from the left contact over the molecule to the right contact. If the device is exposed to light, photon absorption in the molecule might occur, turning the device into a molecular photocell. The photon absorption promotes an electron to higher energy levels and thus modifies the electron transmission probability through the device. A model for such a molecular photocell is presented that minimizes the complexity of the problem while providing a non-trivial description of the device mechanism. In particular, the rolemore » of the molecule in the photocell is investigated. It is described within the Hückel method and the source-sink potential approach [F. Goyer, M. Ernzerhof, and M. Zhuang, J. Chem. Phys. 126, 144104 (2007)] is used to eliminate the contacts in favor of complex-valued potentials. Furthermore, the photons are explicitly incorporated into the model through a second-quantized field. This facilitates the description of the photon absorption process with a stationary state calculation, where eigenvalues and eigenvectors are determined. The model developed is applied to various generic molecular photocells.« less

Molecular structure of dextran sulphate sodium in aqueous environment

NASA Astrophysics Data System (ADS)

Yu, Miao; Every, Hayley A.; Jiskoot, Wim; Witkamp, Geert-Jan; Buijs, Wim

2018-03-01

Here we propose a 3D-molecular structural model for dextran sulphate sodium (DSS) in a neutral aqueous environment based on the results of a molecular modelling study. The DSS structure is dominated by the stereochemistry of the 1,6-linked α-glucose units and the presence of two sulphate groups on each α-glucose unit. The structure of DSS can be best described as a helix with various patterns of di-sulphate substitution on the glucose rings. The presence of a side chain does not alter the 3D-structure of the linear main chain much, but affects the overall spatial dimension of the polymer. The simulated polymers have a diameter similar to or in some cases even larger than model α-hemolysin nano-pores for macromolecule transport in many biological processes, indicating a size-limited translocation through such pores. All results of the molecular modelling study are in line with previously reported experimental data. This study establishes the three-dimensional structure of DSS and summarizes the spatial dimension of the polymer, serving as the basis for a better understanding on the molecular level of DSS-involved electrostatic interaction processes with biological components like proteins and cell pores.

QSPR modeling: graph connectivity indices versus line graph connectivity indices

PubMed

Basak; Nikolic; Trinajstic; Amic; Beslo

2000-07-01

Five QSPR models of alkanes were reinvestigated. Properties considered were molecular surface-dependent properties (boiling points and gas chromatographic retention indices) and molecular volume-dependent properties (molar volumes and molar refractions). The vertex- and edge-connectivity indices were used as structural parameters. In each studied case we computed connectivity indices of alkane trees and alkane line graphs and searched for the optimum exponent. Models based on indices with an optimum exponent and on the standard value of the exponent were compared. Thus, for each property we generated six QSPR models (four for alkane trees and two for the corresponding line graphs). In all studied cases QSPR models based on connectivity indices with optimum exponents have better statistical characteristics than the models based on connectivity indices with the standard value of the exponent. The comparison between models based on vertex- and edge-connectivity indices gave in two cases (molar volumes and molar refractions) better models based on edge-connectivity indices and in three cases (boiling points for octanes and nonanes and gas chromatographic retention indices) better models based on vertex-connectivity indices. Thus, it appears that the edge-connectivity index is more appropriate to be used in the structure-molecular volume properties modeling and the vertex-connectivity index in the structure-molecular surface properties modeling. The use of line graphs did not improve the predictive power of the connectivity indices. Only in one case (boiling points of nonanes) a better model was obtained with the use of line graphs.

A molecular model for proflavine-DNA intercalation.

PubMed Central

Neidle, S; Pearl, L H; Herzyk, P; Berman, H M

1988-01-01

A molecular model has been derived for the intercalation of proflavine into the CpG site of the decamer duplex of d(GATACGATAC). The starting geometry of the intercalation site was taken from previous crystallographic studies on the d(CpG)-proflavine complex, and molecular mechanics used to obtain a stereochemically acceptable structure. This has widened grooves compared to standard A- or B- double helices, as well as distinct conformational, roll, twist and tilt features. PMID:3174439

Molecular description of α-keto-based inhibitors of cruzain with activity against Chagas disease combining 3D-QSAR studies and molecular dynamics.

PubMed

Saraiva, Ádria P B; Miranda, Ricardo M; Valente, Renan P P; Araújo, Jéssica O; Souza, Rutelene N B; Costa, Clauber H S; Oliveira, Amanda R S; Almeida, Michell O; Figueiredo, Antonio F; Ferreira, João E V; Alves, Cláudio Nahum; Honorio, Kathia M

2018-04-22

In this work, a group of α-keto-based inhibitors of the cruzain enzyme with anti-chagas activity was selected for a three-dimensional quantitative structure-activity relationship study (3D-QSAR) combined with molecular dynamics (MD). Firstly, statistical models based on Partial Least Square (PLS) regression were developed employing comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) descriptors. Validation parameters (q 2 and r 2 )for the models were, respectively, 0.910 and 0.997 (CoMFA) and 0.913 and 0.992 (CoMSIA). In addition, external validation for the models using a test group revealed r 2 pred  = 0.728 (CoMFA) and 0.971 (CoMSIA). The most relevant aspect in this study was the generation of molecular fields in both favorable and unfavorable regions based on the models developed. These fields are important to interpret modifications necessary to enhance the biological activities of the inhibitors. This analysis was restricted considering the inhibitors in a fixed conformation, not interacting with their target, the cruzain enzyme. Then, MD was employed taking into account important variables such as time and temperature. MD helped describe the behavior of the inhibitors and their properties showed similar results as those generated by QSAR-3D study. © 2018 John Wiley & Sons A/S.

Molecular basis of structural make-up of feeds in relation to nutrient absorption in ruminants, revealed with advanced molecular spectroscopy: A review on techniques and models

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

Rahman, Md. Mostafizar; Yu, Peiqiang

Progress in ruminant feed research is no more feasible only based on wet chemical analysis, which is merely able to provide information on chemical composition of feeds regardless of their digestive features and nutritive value in ruminants. Studying internal structural make-up of functional groups/feed nutrients is often vital for understanding the digestive behaviors and nutritive values of feeds in ruminant because the intrinsic structure of feed nutrients is more related to its overall absorption. In this article, the detail information on the recent developments in molecular spectroscopic techniques to reveal microstructural information of feed nutrients and the use of nutritionmore » models in regards to ruminant feed research was reviewed. The emphasis of this review was on (1) the technological progress in the use of molecular spectroscopic techniques in ruminant feed research; (2) revealing spectral analysis of functional groups of biomolecules/feed nutrients; (3) the use of advanced nutrition models for better prediction of nutrient availability in ruminant systems; and (4) the application of these molecular techniques and combination of nutrient models in cereals, co-products and pulse crop research. The information described in this article will promote better insight in the progress of research on molecular structural make-up of feed nutrients in ruminants.« less

Molecular docking and 3D-QSAR studies on inhibitors of DNA damage signaling enzyme human PARP-1.

PubMed

Fatima, Sabiha; Bathini, Raju; Sivan, Sree Kanth; Manga, Vijjulatha

2012-08-01

Poly (ADP-ribose) polymerase-1 (PARP-1) operates in a DNA damage signaling network. Molecular docking and three dimensional-quantitative structure activity relationship (3D-QSAR) studies were performed on human PARP-1 inhibitors. Docked conformation obtained for each molecule was used as such for 3D-QSAR analysis. Molecules were divided into a training set and a test set randomly in four different ways, partial least square analysis was performed to obtain QSAR models using the comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). Derived models showed good statistical reliability that is evident from their r², q²(loo) and r²(pred) values. To obtain a consensus for predictive ability from all the models, average regression coefficient r²(avg) was calculated. CoMFA and CoMSIA models showed a value of 0.930 and 0.936, respectively. Information obtained from the best 3D-QSAR model was applied for optimization of lead molecule and design of novel potential inhibitors.

Molecular dynamics-based model of VEGF-A and its heparin interactions.

PubMed

Uciechowska-Kaczmarzyk, Urszula; Babik, Sándor; Zsila, Ferenc; Bojarski, Krzysztof Kamil; Beke-Somfai, Tamás; Samsonov, Sergey A

2018-06-01

We present a computational model of the Vascular Endothelial Growth Factor (VEGF), an important regulator of blood vessels formation, which function is affected by its heparin interactions. Although structures of a receptor binding (RBD) and a heparin binding domain (HBD) of VEGF are known, there are structural data neither on the 12 amino acids interdomain linker nor on its complexes with heparin. We apply molecular docking and molecular dynamics techniques combined with circular dichroism spectroscopy to model the full structure of the dimeric VEGF and to propose putative molecular mechanisms underlying the function of VEGF/VEGF receptors/heparin system. We show that both the conformational flexibility of the linker and the formation of HBD-heparin-HBD sandwich-like structures regulate the mutual disposition of HBDs and so affect the VEGF-mediated signalling. Copyright © 2018 Elsevier Inc. All rights reserved.

Modeling Molecules

NASA Technical Reports Server (NTRS)

2000-01-01

The molecule modeling method known as Multibody Order (N) Dynamics, or MBO(N)D, was developed by Moldyn, Inc. at Goddard Space Flight Center through funding provided by the SBIR program. The software can model the dynamics of molecules through technology which stimulates low-frequency molecular motions and properties, such as movements among a molecule's constituent parts. With MBO(N)D, a molecule is substructured into a set of interconnected rigid and flexible bodies. These bodies replace the computation burden of mapping individual atoms. Moldyn's technology cuts computation time while increasing accuracy. The MBO(N)D technology is available as Insight II 97.0 from Molecular Simulations, Inc. Currently the technology is used to account for forces on spacecraft parts and to perform molecular analyses for pharmaceutical purposes. It permits the solution of molecular dynamics problems on a moderate workstation, as opposed to on a supercomputer.

Treatment of atomic and molecular line blanketing by opacity sampling

NASA Technical Reports Server (NTRS)

Johnson, H. R.; Krupp, B. M.

1976-01-01

A sampling technique for treating the radiative opacity of large numbers of atomic and molecular lines in cool stellar atmospheres is subjected to several tests. In this opacity sampling (OS) technique, the global opacity is sampled at only a selected set of frequencies, and at each of these frequencies the total monochromatic opacity is obtained by summing the contribution of every relevant atomic and molecular line. In accord with previous results, we find that the structure of atmospheric models is accurately fixed by the use of 1000 frequency points, and 100 frequency points are adequate for many purposes. The effects of atomic and molecular lines are separately studied. A test model computed using the OS method agrees very well with a model having identical atmospheric parameters, but computed with the giant line (opacity distribution function) method.

Three-Dimensional Printing of a Scalable Molecular Model and Orbital Kit for Organic Chemistry Teaching and Learning

ERIC Educational Resources Information Center

Penny, Matthew R.; Cao, Zi Jing; Patel, Bhaven; dos Santos, Bruno Sil; Asquith, Christopher R. M.; Szulc, Blanka R.; Rao, Zenobia X.; Muwaffak, Zaid; Malkinson, John P.; Hilton, Stephen T.

2017-01-01

Three-dimensional (3D) chemical models are a well-established learning tool used to enhance the understanding of chemical structures by converting two-dimensional paper or screen outputs into realistic three-dimensional objects. While commercial atom model kits are readily available, there is a surprising lack of large molecular and orbital models…

Multiscale Modeling of Multiphase Fluid Flow

DTIC Science & Technology

2016-08-01

the disparate time and length scales involved in modeling fluid flow and heat transfer. Molecular dynamics simulations were carried out to provide a...fluid dynamics methods were used to investigate the heat transfer process in open-cell micro-foam with phase change material; enhancement of natural...Computational fluid dynamics, Heat transfer, Phase change material in Micro-foam, Molecular Dynamics, Multiphase flow, Multiscale modeling, Natural

A simple theory of molecular organization in fullerene-containing liquid crystals

NASA Astrophysics Data System (ADS)

Peroukidis, S. D.; Vanakaras, A. G.; Photinos, D. J.

2005-10-01

Systematic efforts to synthesize fullerene-containing liquid crystals have produced a variety of successful model compounds. We present a simple molecular theory, based on the interconverting shape approach [Vanakaras and Photinos, J. Mater. Chem. 15, 2002 (2005)], that relates the self-organization observed in these systems to their molecular structure. The interactions are modeled by dividing each molecule into a number of submolecular blocks to which specific interactions are assigned. Three types of blocks are introduced, corresponding to fullerene units, mesogenic units, and nonmesogenic linkage units. The blocks are constrained to move on a cubic three-dimensional lattice and molecular flexibility is allowed by retaining a number of representative conformations within the block representation of the molecule. Calculations are presented for a variety of molecular architectures including twin mesogenic branch monoadducts of C60, twin dendromesogenic branch monoadducts, and conical (badminton shuttlecock) multiadducts of C60. The dependence of the phase diagrams on the interaction parameters is explored. In spite of its many simplifications and the minimal molecular modeling used (three types of chemically distinct submolecular blocks with only repulsive interactions), the theory accounts remarkably well for the phase behavior of these systems.

Model for diffuse interstellar clouds: improvements to the theory of molecular hydrogen photodestruction and to the gas phase chemistry of carbon monoxide

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

Federman, S.R.

1979-01-01

A theoretical model has been developed to determine physical processes in conjunction with astrophysical observation. The calculations are based on isobaric, steady-state, plane-parallel conditions. In the model, the cloud is illuminated by ultraviolet radiation from one side. The density and temperature of the gas are derived by invoking energy conservation in terms of thermal balance. The derived values for density and temperature then are used to determine the abundances of approximately fifty atomic and molecular species, including important ionic species and simple carbon and oxygen bearing molecules. Except for molecular hydrogen formation on dust grains, binary gas phase reactions aremore » used to develop the chemistry of the model cloud. The theoretical model has been found to be appropriate for a particular range of physical parameters. The results of the steady-state calculations have been compared to ultraviolet observations, predominantly those made with the Copernicus satellite. The theory of molecular hydrogen photodestruction has been reexamined so that improvements to the model can be made. By analyzing the region where the atomic to molecuar hydrogen transition occurs, several processes have been found to contribute to dissociation.« less

A theoretical-electron-density databank using a model of real and virtual spherical atoms.

PubMed

Nassour, Ayoub; Domagala, Slawomir; Guillot, Benoit; Leduc, Theo; Lecomte, Claude; Jelsch, Christian

2017-08-01

A database describing the electron density of common chemical groups using combinations of real and virtual spherical atoms is proposed, as an alternative to the multipolar atom modelling of the molecular charge density. Theoretical structure factors were computed from periodic density functional theory calculations on 38 crystal structures of small molecules and the charge density was subsequently refined using a density model based on real spherical atoms and additional dummy charges on the covalent bonds and on electron lone-pair sites. The electron-density parameters of real and dummy atoms present in a similar chemical environment were averaged on all the molecules studied to build a database of transferable spherical atoms. Compared with the now-popular databases of transferable multipolar parameters, the spherical charge modelling needs fewer parameters to describe the molecular electron density and can be more easily incorporated in molecular modelling software for the computation of electrostatic properties. The construction method of the database is described. In order to analyse to what extent this modelling method can be used to derive meaningful molecular properties, it has been applied to the urea molecule and to biotin/streptavidin, a protein/ligand complex.

THE IMPACT OF MOLECULAR GAS ON MASS MODELS OF NEARBY GALAXIES

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

Frank, B. S.; Blok, W. J. G. de; Walter, F.

2016-04-15

We present CO velocity fields and rotation curves for a sample of nearby galaxies, based on data from HERACLES. We combine our data with THINGS, SINGS, and KINGFISH results to provide a comprehensive sample of mass models of disk galaxies inclusive of molecular gas. We compare the kinematics of the molecular (CO from HERACLES) and atomic (H i from THINGS) gas distributions to determine the extent to which CO may be used to probe the dynamics in the inner part of galaxies. In general, we find good agreement between the CO and H i kinematics, with small differences in themore » inner part of some galaxies. We add the contribution of the molecular gas to the mass models in our galaxies by using two different conversion factors α{sub CO} to convert CO luminosity to molecular gas mass surface density—the constant Milky Way value and the radially varying profiles determined in recent work based on THINGS, HERACLES, and KINGFISH data. We study the relative effect that the addition of the molecular gas has on the halo rotation curves for Navarro–Frenk–White and the observationally motivated pseudo-isothermal halos. The contribution of the molecular gas varies for galaxies in our sample—for those galaxies where there is a substantial molecular gas content, using different values of α{sub CO} can result in significant differences to the relative contribution of the molecular gas and hence the shape of the dark matter halo rotation curves in the central regions of galaxies.« less

Targeting CYP51 for drug design by the contributions of molecular modeling.

PubMed

Rabelo, Vitor W; Santos, Taísa F; Terra, Luciana; Santana, Marcos V; Castro, Helena C; Rodrigues, Carlos R; Abreu, Paula A

2017-02-01

CYP51 is an enzyme of sterol biosynthesis pathway present in animals, plants, protozoa and fungi. This enzyme is described as an important drug target that is still of interest. Therefore, in this work, we reviewed the structure and function of CYP51 and explored the molecular modeling approaches for the development of new antifungal and antiprotozoans that target this enzyme. Crystallographic structures of CYP51 of some organisms have already been described in the literature, which enable the construction of homology models of other organisms' enzymes and molecular docking studies of new ligands. The binding mode and interactions of some new series of azoles with antifungal or antiprotozoan activities has been studied and showed important residues of the active site. Molecular modeling is an important tool to be explored for the discovery and optimization of CYP51 inhibitors with better activities, pharmacokinetics, and toxicological profiles. © 2016 Société Française de Pharmacologie et de Thérapeutique.

Automated building of organometallic complexes from 3D fragments.

PubMed

Foscato, Marco; Venkatraman, Vishwesh; Occhipinti, Giovanni; Alsberg, Bjørn K; Jensen, Vidar R

2014-07-28

A method for the automated construction of three-dimensional (3D) molecular models of organometallic species in design studies is described. Molecular structure fragments derived from crystallographic structures and accurate molecular-level calculations are used as 3D building blocks in the construction of multiple molecular models of analogous compounds. The method allows for precise control of stereochemistry and geometrical features that may otherwise be very challenging, or even impossible, to achieve with commonly available generators of 3D chemical structures. The new method was tested in the construction of three sets of active or metastable organometallic species of catalytic reactions in the homogeneous phase. The performance of the method was compared with those of commonly available methods for automated generation of 3D models, demonstrating higher accuracy of the prepared 3D models in general, and, in particular, a much wider range with respect to the kind of chemical structures that can be built automatically, with capabilities far beyond standard organic and main-group chemistry.

The brain as a system of nested but partially overlapping networks. Heuristic relevance of the model for brain physiology and pathology.

PubMed

Agnati, L F; Guidolin, D; Fuxe, K

2007-01-01

A new model of the brain organization is proposed. The model is based on the assumption that a global molecular network enmeshes the entire central nervous system. Thus, brain extra-cellular and intra-cellular molecular networks are proposed to communicate at the level of special plasma membrane regions (e.g., the lipid rafts) where horizontal molecular networks can represent input/output regions allowing the cell to have informational exchanges with the extracellular environment. Furthermore, some "pervasive signals" such as field potentials, pressure waves and thermal gradients that affect large parts of the brain cellular and molecular networks are discussed. Finally, at least two learning paradigms are analyzed taking into account the possible role of Volume Transmission: the so-called model of "temporal difference learning" and the "Turing B-unorganised machine". The relevance of this new view of brain organization for a deeper understanding of some neurophysiological and neuropathological aspects of its function is briefly discussed.

Molecular dissection of colorectal cancer in pre-clinical models identifies biomarkers predicting sensitivity to EGFR inhibitors

PubMed Central

Schütte, Moritz; Risch, Thomas; Abdavi-Azar, Nilofar; Boehnke, Karsten; Schumacher, Dirk; Keil, Marlen; Yildiriman, Reha; Jandrasits, Christine; Borodina, Tatiana; Amstislavskiy, Vyacheslav; Worth, Catherine L.; Schweiger, Caroline; Liebs, Sandra; Lange, Martin; Warnatz, Hans- Jörg; Butcher, Lee M.; Barrett, James E.; Sultan, Marc; Wierling, Christoph; Golob-Schwarzl, Nicole; Lax, Sigurd; Uranitsch, Stefan; Becker, Michael; Welte, Yvonne; Regan, Joseph Lewis; Silvestrov, Maxine; Kehler, Inge; Fusi, Alberto; Kessler, Thomas; Herwig, Ralf; Landegren, Ulf; Wienke, Dirk; Nilsson, Mats; Velasco, Juan A.; Garin-Chesa, Pilar; Reinhard, Christoph; Beck, Stephan; Schäfer, Reinhold; Regenbrecht, Christian R. A.; Henderson, David; Lange, Bodo; Haybaeck, Johannes; Keilholz, Ulrich; Hoffmann, Jens; Lehrach, Hans; Yaspo, Marie-Laure

2017-01-01

Colorectal carcinoma represents a heterogeneous entity, with only a fraction of the tumours responding to available therapies, requiring a better molecular understanding of the disease in precision oncology. To address this challenge, the OncoTrack consortium recruited 106 CRC patients (stages I–IV) and developed a pre-clinical platform generating a compendium of drug sensitivity data totalling >4,000 assays testing 16 clinical drugs on patient-derived in vivo and in vitro models. This large biobank of 106 tumours, 35 organoids and 59 xenografts, with extensive omics data comparing donor tumours and derived models provides a resource for advancing our understanding of CRC. Models recapitulate many of the genetic and transcriptomic features of the donors, but defined less complex molecular sub-groups because of the loss of human stroma. Linking molecular profiles with drug sensitivity patterns identifies novel biomarkers, including a signature outperforming RAS/RAF mutations in predicting sensitivity to the EGFR inhibitor cetuximab. PMID:28186126

Ab initio solution of macromolecular crystal structures without direct methods.

PubMed

McCoy, Airlie J; Oeffner, Robert D; Wrobel, Antoni G; Ojala, Juha R M; Tryggvason, Karl; Lohkamp, Bernhard; Read, Randy J

2017-04-04

The majority of macromolecular crystal structures are determined using the method of molecular replacement, in which known related structures are rotated and translated to provide an initial atomic model for the new structure. A theoretical understanding of the signal-to-noise ratio in likelihood-based molecular replacement searches has been developed to account for the influence of model quality and completeness, as well as the resolution of the diffraction data. Here we show that, contrary to current belief, molecular replacement need not be restricted to the use of models comprising a substantial fraction of the unknown structure. Instead, likelihood-based methods allow a continuum of applications depending predictably on the quality of the model and the resolution of the data. Unexpectedly, our understanding of the signal-to-noise ratio in molecular replacement leads to the finding that, with data to sufficiently high resolution, fragments as small as single atoms of elements usually found in proteins can yield ab initio solutions of macromolecular structures, including some that elude traditional direct methods.

Molecular dynamics simulations for mechanical properties of borophene: parameterization of valence force field model and Stillinger-Weber potential

PubMed Central

Zhou, Yu-Ping; Jiang, Jin-Wu

2017-01-01

While most existing theoretical studies on the borophene are based on first-principles calculations, the present work presents molecular dynamics simulations for the lattice dynamical and mechanical properties in borophene. The obtained mechanical quantities are in good agreement with previous first-principles calculations. The key ingredients for these molecular dynamics simulations are the two efficient empirical potentials developed in the present work for the interaction of borophene with low-energy triangular structure. The first one is the valence force field model, which is developed with the assistance of the phonon dispersion of borophene. The valence force field model is a linear potential, so it is rather efficient for the calculation of linear quantities in borophene. The second one is the Stillinger-Weber potential, whose parameters are derived based on the valence force field model. The Stillinger-Weber potential is applicable in molecular dynamics simulations of nonlinear physical or mechanical quantities in borophene. PMID:28349983

Is there hope for multi-site complexation modeling?

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

Bickmore, Barry R.; Rosso, Kevin M.; Mitchell, S. C.

2006-06-06

It has been shown here that the standard formulation of the MUSIC model does not deliver the molecular-scale insight into oxide surface reactions that it promises. The model does not properly divide long-range electrostatic and short-range contributions to acid-base reaction energies, and it does not treat solvation in a physically realistic manner. However, even if the current MUSIC model does not succeed in its ambitions, its ambitions are still reasonable. It was a pioneering attempt in that Hiemstra and coworkers recognized that intrinsic equilibrium constants, where the effects of long-range electrostatic effects have been removed, must be theoretically constrained priormore » to model fitting if there is to be any hope of obtaining molecular-scale insights from SCMs. We have also shown, on the other hand, that it may be premature to dismiss all valence-based models of acidity. Not only can some such models accurately predict intrinsic acidity constants, but they can also now be linked to the results of molecular dynamics simulations of solvated systems. Significant challenges remain for those interested in creating SCMs that are accurate at the molecular scale. It will only be after all model parameters can be predicted from theory, and the models validated against titration data that we will be able to begin to have some confidence that we really are adequately describing the chemical systems in question.« less

Homology modeling, molecular docking and MD simulation studies to investigate role of cysteine protease from Xanthomonas campestris in degradation of Aβ peptide.

PubMed

Dhanavade, Maruti J; Jalkute, Chidambar B; Barage, Sagar H; Sonawane, Kailas D

2013-12-01

Cysteine protease is known to degrade amyloid beta peptide which is a causative agent of Alzheimer's disease. This cleavage mechanism has not been studied in detail at the atomic level. Hence, a three-dimensional structure of cysteine protease from Xanthomonas campestris was constructed by homology modeling using Geno3D, SWISS-MODEL, and MODELLER 9v7. All the predicted models were analyzed by PROCHECK and PROSA. Three-dimensional model of cysteine protease built by MODELLER 9v7 shows similarity with human cathepsin B crystal structure. This model was then used further for docking and simulation studies. The molecular docking study revealed that Cys17, His87, and Gln88 residues of cysteine protease form an active site pocket similar to human cathepsin B. Then the docked complex was refined by molecular dynamic simulation to confirm its stable behavior over the entire simulation period. The molecular docking and MD simulation studies showed that the sulfhydryl hydrogen atom of Cys17 of cysteine protease interacts with carboxylic oxygen of Lys16 of Aβ peptide indicating the cleavage site. Thus, the cysteine protease model from X. campestris having similarity with human cathepsin B crystal structure may be used as an alternate approach to cleave Aβ peptide a causative agent of Alzheimer's disease. © 2013 Elsevier Ltd. All rights reserved.

Hierarchical modeling of molecular energies using a deep neural network

NASA Astrophysics Data System (ADS)

Lubbers, Nicholas; Smith, Justin S.; Barros, Kipton

2018-06-01

We introduce the Hierarchically Interacting Particle Neural Network (HIP-NN) to model molecular properties from datasets of quantum calculations. Inspired by a many-body expansion, HIP-NN decomposes properties, such as energy, as a sum over hierarchical terms. These terms are generated from a neural network—a composition of many nonlinear transformations—acting on a representation of the molecule. HIP-NN achieves the state-of-the-art performance on a dataset of 131k ground state organic molecules and predicts energies with 0.26 kcal/mol mean absolute error. With minimal tuning, our model is also competitive on a dataset of molecular dynamics trajectories. In addition to enabling accurate energy predictions, the hierarchical structure of HIP-NN helps to identify regions of model uncertainty.

Computer display and manipulation of biological molecules

NASA Technical Reports Server (NTRS)

Coeckelenbergh, Y.; Macelroy, R. D.; Hart, J.; Rein, R.

1978-01-01

This paper describes a computer model that was designed to investigate the conformation of molecules, macromolecules and subsequent complexes. Utilizing an advanced 3-D dynamic computer display system, the model is sufficiently versatile to accommodate a large variety of molecular input and to generate data for multiple purposes such as visual representation of conformational changes, and calculation of conformation and interaction energy. Molecules can be built on the basis of several levels of information. These include the specification of atomic coordinates and connectivities and the grouping of building blocks and duplicated substructures using symmetry rules found in crystals and polymers such as proteins and nucleic acids. Called AIMS (Ames Interactive Molecular modeling System), the model is now being used to study pre-biotic molecular evolution toward life.

Lego bricks and the octet rule: Molecular models for biochemical pathways with plastic, interlocking toy bricks.

PubMed

Lin, Henry J; Lehoang, Jennifer; Kwan, Isabel; Baghaee, Anita; Prasad, Priya; Ha-Chen, Stephanie J; Moss, Tanesha; Woods, Jeremy D

2018-01-01

The 8 studs on a 2 × 4 Lego brick conveniently represent the outer shell of electrons for carbon, nitrogen, and oxygen atoms. We used Lego bricks to model these atoms, which are then joined together to form molecules by following the Lewis octet rule. A variety of small biological molecules can be modeled in this way, such as most amino acids, fatty acids, glucose, and various intermediate metabolites. Model building with these familiar toys can be a helpful, hands-on exercise for learning-or re-learning-biochemical pathways. © 2017 by The International Union of Biochemistry and Molecular Biology, 46(1):54-57, 2018. © 2017 The International Union of Biochemistry and Molecular Biology.

Modeling the relationship between body weight and energy intake: A molecular diffusion-based approach

PubMed Central

2012-01-01

Background Body weight is at least partly controlled by the choices made by a human in response to external stimuli. Changes in body weight are mainly caused by energy intake. By analyzing the mechanisms involved in food intake, we considered that molecular diffusion plays an important role in body weight changes. We propose a model based on Fick's second law of diffusion to simulate the relationship between energy intake and body weight. Results This model was applied to food intake and body weight data recorded in humans; the model showed a good fit to the experimental data. This model was also effective in predicting future body weight. Conclusions In conclusion, this model based on molecular diffusion provides a new insight into the body weight mechanisms. Reviewers This article was reviewed by Dr. Cabral Balreira (nominated by Dr. Peter Olofsson), Prof. Yang Kuang and Dr. Chao Chen. PMID:22742862

Transport properties and efficiency of elastically coupled particles in asymmetric periodic potentials

NASA Astrophysics Data System (ADS)

Igarashi, Akito; Tsukamoto, Shinji

2000-02-01

Biological molecular motors drive unidirectional transport and transduce chemical energy to mechanical work. In order to identify this energy conversion which is a common feature of molecular motors, many workers have studied various physical models, which consist of Brownian particles in spatially periodic potentials. Most of the models are, however, based on "single-particle" dynamics and too simple as models for biological motors, especially for actin-myosin motors, which cause muscle contraction. In this paper, particles coupled by elastic strings in an asymmetric periodic potential are considered as a model for the motors. We investigate the dynamics of the model and calculate the efficiency of energy conversion with the use of molecular dynamical method. In particular, we find that the velocity and efficiency of the elastically coupled particles where the natural length of the springs is incommensurable with the period of the periodic potential are larger than those of the corresponding single particle model.

Simulating the flow of entangled polymers.

PubMed

Masubuchi, Yuichi

2014-01-01

To optimize automation for polymer processing, attempts have been made to simulate the flow of entangled polymers. In industry, fluid dynamics simulations with phenomenological constitutive equations have been practically established. However, to account for molecular characteristics, a method to obtain the constitutive relationship from the molecular structure is required. Molecular dynamics simulations with atomic description are not practical for this purpose; accordingly, coarse-grained models with reduced degrees of freedom have been developed. Although the modeling of entanglement is still a challenge, mesoscopic models with a priori settings to reproduce entangled polymer dynamics, such as tube models, have achieved remarkable success. To use the mesoscopic models as staging posts between atomistic and fluid dynamics simulations, studies have been undertaken to establish links from the coarse-grained model to the atomistic and macroscopic simulations. Consequently, integrated simulations from materials chemistry to predict the macroscopic flow in polymer processing are forthcoming.

An Insilico Design of Nanoclay Based Nanocomposites and Scaffolds in Bone Tissue Engineering

NASA Astrophysics Data System (ADS)

Sharma, Anurag

A multiscale in silico approach to design polymer nanocomposites and scaffolds for bone tissue engineering applications is described in this study. This study focuses on the role of biomaterials design and selection, structural integrity and mechanical properties evolution during degradation and tissue regeneration in the successful design of polymer nanocomposite scaffolds. Polymer nanocomposite scaffolds are synthesized using aminoacid modified montmorillonite nanoclay with biomineralized hydroxyapatite and polycaprolactone (PCL/in situ HAPclay). Representative molecular models of polymer nanocomposite system are systematically developed using molecular dynamics (MD) technique and successfully validated using material characterization techniques. The constant force steered molecular dynamics (fSMD) simulation results indicate a two-phase nanomechanical behavior of the polymer nanocomposite. The MD and fSMD simulations results provide quantitative contributions of molecular interactions between different constituents of representative models and their effect on nanomechanical responses of nanoclay based polymer nanocomposite system. A finite element (FE) model of PCL/in situ HAPclay scaffold is built using micro-computed tomography images and bridging the nanomechanical properties obtained from fSMD simulations into the FE model. A new reduction factor, K is introduced into modeling results to consider the effect of wall porosity of the polymer scaffold. The effect of accelerated degradation under alkaline conditions and human osteoblast cells culture on the evolution of mechanical properties of scaffolds are studied and the damage mechanics based analytical models are developed. Finally, the novel multiscale models are developed that incorporate the complex molecular and microstructural properties, mechanical properties at nanoscale and structural levels and mechanical properties evolution during degradation and tissue formation in the polymer nanocomposite scaffold. Overall, this study provides a leap into methodologies for in silico design of biomaterials for bone tissue engineering applications. Furthermore, as a part of this work, a molecular dynamics study of rice DNA in the presence of single walled carbon nanotube is carried out to understand the role played by molecular interactions in the conformation changes of rice DNA. The simulations results showed wrapping of DNA onto SWCNT, breaking and forming of hydrogen bonds due to unzipping of Watson-Crick (WC) nucleobase pairs and forming of new non-WC nucleobase pairs in DNA.

Study of clathrate hydrates via equilibrium molecular-dynamics simulation employing polarisable and non-polarisable, rigid and flexible water models

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

Burnham, Christian J., E-mail: christian.burnham@ucd.ie, E-mail: niall.english@ucd.ie; English, Niall J., E-mail: christian.burnham@ucd.ie, E-mail: niall.english@ucd.ie

Equilibrium molecular-dynamics (MD) simulations have been performed on metastable sI and sII polymorphs of empty hydrate lattices, in addition to liquid water and ice Ih. The non-polarisable TIP4P-2005, simple point charge model (SPC), and polarisable Thole-type models (TTM): TTM2, TTM3, and TTM4 water models were used in order to survey the differences between models and to see what differences can be expected when polarisability is incorporated. Rigid and flexible variants were used of each model to gauge the effects of flexibility. Power spectra are calculated and compared to density-of-states spectra inferred from inelastic neutron scattering (INS) measurements. Thermodynamic properties weremore » also calculated, as well as molecular-dipole distributions. It was concluded that TTM models offer optimal fidelity vis-à-vis INS spectra, together with thermodynamic properties, with the flexible TTM2 model offering optimal placement of vibrational modes.« less

Quantitative computational models of molecular self-assembly in systems biology

PubMed Central

Thomas, Marcus; Schwartz, Russell

2017-01-01

Molecular self-assembly is the dominant form of chemical reaction in living systems, yet efforts at systems biology modeling are only beginning to appreciate the need for and challenges to accurate quantitative modeling of self-assembly. Self-assembly reactions are essential to nearly every important process in cell and molecular biology and handling them is thus a necessary step in building comprehensive models of complex cellular systems. They present exceptional challenges, however, to standard methods for simulating complex systems. While the general systems biology world is just beginning to deal with these challenges, there is an extensive literature dealing with them for more specialized self-assembly modeling. This review will examine the challenges of self-assembly modeling, nascent efforts to deal with these challenges in the systems modeling community, and some of the solutions offered in prior work on self-assembly specifically. The review concludes with some consideration of the likely role of self-assembly in the future of complex biological system models more generally. PMID:28535149

Quantitative computational models of molecular self-assembly in systems biology.

PubMed

Thomas, Marcus; Schwartz, Russell

2017-05-23

Molecular self-assembly is the dominant form of chemical reaction in living systems, yet efforts at systems biology modeling are only beginning to appreciate the need for and challenges to accurate quantitative modeling of self-assembly. Self-assembly reactions are essential to nearly every important process in cell and molecular biology and handling them is thus a necessary step in building comprehensive models of complex cellular systems. They present exceptional challenges, however, to standard methods for simulating complex systems. While the general systems biology world is just beginning to deal with these challenges, there is an extensive literature dealing with them for more specialized self-assembly modeling. This review will examine the challenges of self-assembly modeling, nascent efforts to deal with these challenges in the systems modeling community, and some of the solutions offered in prior work on self-assembly specifically. The review concludes with some consideration of the likely role of self-assembly in the future of complex biological system models more generally.

The impact of chemical structure and molecular packing on the electronic polarisation of fullerene arrays.

PubMed

Few, Sheridan; Chia, Cleaven; Teo, Daniel; Kirkpatrick, James; Nelson, Jenny

2017-07-19

Electronic polarisation contributes to the electronic landscape as seen by separating charges in organic materials. The nature of electronic polarisation depends on the polarisability, density, and arrangement of polarisable molecules. In this paper, we introduce a microscopic, coarse-grained model in which we treat each molecule as a polarisable site, and use an array of such polarisable dipoles to calculate the electric field and associated energy of any arrangement of charges in the medium. The model incorporates chemical structure via the molecular polarisability and molecular packing patterns via the structure of the array. We use this model to calculate energies of charge pairs undergoing separation in finite fullerene lattices of different chemical and crystal structures. The effective dielectric constants that we estimate from this approach are in good quantitative agreement with those measured experimentally in C 60 and phenyl-C 61 -butyric acid methyl ester (PCBM) films, but we find significant differences in dielectric constant depending on packing and on direction of separation, which we rationalise in terms of density of polarisable fullerene cages in regions of high field. In general, we find lattices containing molecules of more isotropic polarisability tensors exhibit higher dielectric constants. By exploring several model systems we conclude that differences in molecular polarisability (and therefore, chemical structure) appear to be less important than differences in molecular packing and separation direction in determining the energetic landscape for charge separation. We note that the results are relevant for finite lattices, but not necessarily for infinite systems. We propose that the model could be used to design molecular systems for effective electronic screening.

Insight into the interaction mechanism of human SGLT2 with its inhibitors: 3D-QSAR studies, homology modeling, and molecular docking and molecular dynamics simulations.

PubMed

Dong, Lili; Feng, Ruirui; Bi, Jiawei; Shen, Shengqiang; Lu, Huizhe; Zhang, Jianjun

2018-03-06

Human sodium-dependent glucose co-transporter 2 (hSGLT2) is a crucial therapeutic target in the treatment of type 2 diabetes. In this study, both comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were applied to generate three-dimensional quantitative structure-activity relationship (3D-QSAR) models. In the most accurate CoMFA-based and CoMSIA-based QSAR models, the cross-validated coefficients (r 2 cv ) were 0.646 and 0.577, respectively, while the non-cross-validated coefficients (r 2 ) were 0.997 and 0.991, respectively, indicating that both models were reliable. In addition, we constructed a homology model of hSGLT2 in the absence of a crystal structure. Molecular docking was performed to explore the bonding mode of inhibitors to the active site of hSGLT2. Molecular dynamics (MD) simulations and binding free energy calculations using MM-PBSA and MM-GBSA were carried out to further elucidate the interaction mechanism. With regards to binding affinity, we found that hydrogen-bond interactions of Asn51 and Glu75, located in the active site of hSGLT2, with compound 40 were critical. Hydrophobic and electrostatic interactions were shown to enhance activity, in agreement with the results obtained from docking and 3D-QSAR analysis. Our study results shed light on the interaction mode between inhibitors and hSGLT2 and may aid in the development of C-aryl glucoside SGLT2 inhibitors.

Molecular modeling studies of 1,4-dihydro-4-oxoquinoline ribonucleosides with anti-HSV-1 activity

NASA Astrophysics Data System (ADS)

Yoneda, Julliane Diniz; Albuquerque, Magaly Girão; Leal, Kátia Zaccur; Seidl, Peter Rudolf; de Alencastro, Ricardo Bicca

2011-12-01

Eight human herpes viruses ( e.g., herpes simplex, varicella-zoster, Epstein-Barr, cytomegalovirus, Kaposi's sarcoma) are responsible for several diseases from sub-clinic manifestations to fatal infections, mostly in immunocompromised patients. The major limitations of the currently available antiviral drug therapy are drug resistance, host toxicity, and narrow spectrum of activity. However, some non-nucleoside 1,4-dihydro-4-oxoquinoline derivatives ( e.g., PNU-183792) [4] shows broad spectrum antiviral activity. We have developed molecular modeling studies, including molecular docking and molecular dynamics simulations, based on a model proposed by Liu and co-workers [14] in order to understand the mechanism of action of a 6-chloro substituted 1,4-dihydro-4-oxoquinoline ribonucleoside, synthesized by the synthetic group, which showed anti-HSV-1 activity [9]. The molecular docking simulations confirmed the Liu's model showing that the ligand needs to dislocate template residues from the active site in order to interact with the viral DNA polymerase enzyme, reinforcing that the interaction with the Val823 residue is pivotal for the inhibitory activity of non-nucleoside 1,4-dihydro-4-oxoquinoline derivatives, such as PNU-183792, with the HSV-1. The molecular dynamics simulations showed that the 6-chloro-benzyl group of PNU-183792 maintains its interaction with residues of the HSV-1 DNA polymerase hydrophobic pocket, considered important according to the Liu's model, and also showed that the methyl group bounded to the nitrogen atom from PNU-183792 is probably contributing to a push-pull effect with the carbonyl group.

Thermodynamic properties for applications in chemical industry via classical force fields.

PubMed

Guevara-Carrion, Gabriela; Hasse, Hans; Vrabec, Jadran

2012-01-01

Thermodynamic properties of fluids are of key importance for the chemical industry. Presently, the fluid property models used in process design and optimization are mostly equations of state or G (E) models, which are parameterized using experimental data. Molecular modeling and simulation based on classical force fields is a promising alternative route, which in many cases reasonably complements the well established methods. This chapter gives an introduction to the state-of-the-art in this field regarding molecular models, simulation methods, and tools. Attention is given to the way modeling and simulation on the scale of molecular force fields interact with other scales, which is mainly by parameter inheritance. Parameters for molecular force fields are determined both bottom-up from quantum chemistry and top-down from experimental data. Commonly used functional forms for describing the intra- and intermolecular interactions are presented. Several approaches for ab initio to empirical force field parameterization are discussed. Some transferable force field families, which are frequently used in chemical engineering applications, are described. Furthermore, some examples of force fields that were parameterized for specific molecules are given. Molecular dynamics and Monte Carlo methods for the calculation of transport properties and vapor-liquid equilibria are introduced. Two case studies are presented. First, using liquid ammonia as an example, the capabilities of semi-empirical force fields, parameterized on the basis of quantum chemical information and experimental data, are discussed with respect to thermodynamic properties that are relevant for the chemical industry. Second, the ability of molecular simulation methods to describe accurately vapor-liquid equilibrium properties of binary mixtures containing CO(2) is shown.

Combined 3D-QSAR, molecular docking and molecular dynamics study on thyroid hormone activity of hydroxylated polybrominated diphenyl ethers to thyroid receptors β

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

Li, Xiaolin; Ye, Li; Wang, Xiaoxiang

2012-12-15

Several recent reports suggested that hydroxylated polybrominated diphenyl ethers (HO-PBDEs) may disturb thyroid hormone homeostasis. To illuminate the structural features for thyroid hormone activity of HO-PBDEs and the binding mode between HO-PBDEs and thyroid hormone receptor (TR), the hormone activity of a series of HO-PBDEs to thyroid receptors β was studied based on the combination of 3D-QSAR, molecular docking, and molecular dynamics (MD) methods. The ligand- and receptor-based 3D-QSAR models were obtained using Comparative Molecular Similarity Index Analysis (CoMSIA) method. The optimum CoMSIA model with region focusing yielded satisfactory statistical results: leave-one-out cross-validation correlation coefficient (q{sup 2}) was 0.571 andmore » non-cross-validation correlation coefficient (r{sup 2}) was 0.951. Furthermore, the results of internal validation such as bootstrapping, leave-many-out cross-validation, and progressive scrambling as well as external validation indicated the rationality and good predictive ability of the best model. In addition, molecular docking elucidated the conformations of compounds and key amino acid residues at the docking pocket, MD simulation further determined the binding process and validated the rationality of docking results. -- Highlights: ► The thyroid hormone activities of HO-PBDEs were studied by 3D-QSAR. ► The binding modes between HO-PBDEs and TRβ were explored. ► 3D-QSAR, molecular docking, and molecular dynamics (MD) methods were performed.« less

Interaction of methotrexate with trypsin analyzed by spectroscopic and molecular modeling methods

NASA Astrophysics Data System (ADS)

Wang, Yanqing; Zhang, Hongmei; Cao, Jian; Zhou, Qiuhua

2013-11-01

Trypsin is one of important digestive enzymes that have intimate correlation with human health and illness. In this work, the interaction of trypsin with methotrexate was investigated by spectroscopic and molecular modeling methods. The results revealed that methotrexate could interact with trypsin with about one binding site. Methotrexate molecule could enter into the primary substrate-binding pocket, resulting in inhibition of trypsin activity. Furthermore, the thermodynamic analysis implied that electrostatic force, hydrogen bonding, van der Waals and hydrophobic interactions were the main interactions for stabilizing the trypsin-methotrexate system, which agreed well with the results from the molecular modeling study.

From Reactor to Rheology in LDPE Modeling

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

Read, Daniel J.; Das, Chinmay; Auhl, Dietmar

2008-07-07

In recent years the association between molecular structure and linear rheology has been established and well-understood through the tube concept and its extensions for well-characterized materials (e.g. McLeish, Adv. Phys. 2002). However, for industrial branched polymeric material at processing conditions this piece of information is missing. A large number of phenomenological models have been developed to describe the nonlinear response of polymers. But none of these models takes into account the underlying molecular structure, leading to a fitting procedure with arbitrary fitting parameters. The goal of applied molecular rheology is a predictive scheme that runs in its entirety from themore » molecular structure from the reactor to the non-linear rheology of the resin. In our approach, we use a model for the industrial reactor to explicitly generate the molecular structure ensemble of LDPE's, (Tobita, J. Polym. Sci. B 2001), which are consistent with the analytical information. We calculate the linear rheology of the LDPE ensemble with the use of a tube model for branched polymers (Das et al., J. Rheol. 2006). We then, separate the contribution of the stress decay to a large number of pompom modes (McLeish et al., J. Rheol. 1998 and Inkson et al., J. Rheol. 1999) with the stretch time and the priority variables corresponding to the actual ensemble of molecules involved. This multimode pompom model allows us to predict the nonlinear properties without any fitting parameter. We present and analyze our results in comparison with experimental data on industrial materials.« less

Moving Beyond the Single Center--Ways to Reinforce Molecular Orbital Theory in an Inorganic Course

ERIC Educational Resources Information Center

Cass, Marion E.; Hollingsworth, William E.

2004-01-01

It is suggested that molecular theory should be taught earlier in the inorganic chemistry curriculum even in the introductory chemistry course in order to integrate molecular orbital arguments more effectively throughout the curriculum. The method of teaching relies on having access to molecular modeling software as having access to such software…

Toll-Like Receptor-9-Mediated Invasion in Breast Cancer

DTIC Science & Technology

2011-07-01

Molecular Dynamics Simulations. Theoretical structural models were obtained from molecular dynamics simulations using explicit solvation by...with AMBER by MARDIGRAS. The solution structure was then derived by coupling the resulting NMR distance restraints with a molecular dynamic ...Overlay of NMR restrained structure (red) with theoretical molecular dynamic simulated annealing structure (blue). Energetic stability of the 9-mer

Phaser.MRage: automated molecular replacement

PubMed Central

Bunkóczi, Gábor; Echols, Nathaniel; McCoy, Airlie J.; Oeffner, Robert D.; Adams, Paul D.; Read, Randy J.

2013-01-01

Phaser.MRage is a molecular-replacement automation framework that implements a full model-generation workflow and provides several layers of model exploration to the user. It is designed to handle a large number of models and can distribute calculations efficiently onto parallel hardware. In addition, phaser.MRage can identify correct solutions and use this information to accelerate the search. Firstly, it can quickly score all alternative models of a component once a correct solution has been found. Secondly, it can perform extensive analysis of identified solutions to find protein assemblies and can employ assembled models for subsequent searches. Thirdly, it is able to use a priori assembly information (derived from, for example, homologues) to speculatively place and score molecules, thereby customizing the search procedure to a certain class of protein molecule (for example, antibodies) and incorporating additional biological information into molecular replacement. PMID:24189240

Phaser.MRage: automated molecular replacement.

PubMed

Bunkóczi, Gábor; Echols, Nathaniel; McCoy, Airlie J; Oeffner, Robert D; Adams, Paul D; Read, Randy J

2013-11-01

Phaser.MRage is a molecular-replacement automation framework that implements a full model-generation workflow and provides several layers of model exploration to the user. It is designed to handle a large number of models and can distribute calculations efficiently onto parallel hardware. In addition, phaser.MRage can identify correct solutions and use this information to accelerate the search. Firstly, it can quickly score all alternative models of a component once a correct solution has been found. Secondly, it can perform extensive analysis of identified solutions to find protein assemblies and can employ assembled models for subsequent searches. Thirdly, it is able to use a priori assembly information (derived from, for example, homologues) to speculatively place and score molecules, thereby customizing the search procedure to a certain class of protein molecule (for example, antibodies) and incorporating additional biological information into molecular replacement.

Dielectric Properties of Piezoelectric Polyimides

NASA Technical Reports Server (NTRS)

Ounaies, Z.; Young, J. A.; Simpson, J. O.; Farmer, B. L.

1997-01-01

Molecular modeling and dielectric measurements are being used to identify mechanisms governing piezoelectric behavior in polyimides such as dipole orientation during poling, as well as degree of piezoelectricity achievable. Molecular modeling on polyimides containing pendant, polar nitrile (CN) groups has been completed to determine their remanent polarization. Experimental investigation of their dielectric properties evaluated as a function of temperature and frequency has substantiated numerical predictions. With this information in hand, we are then able to suggest changes in the molecular structures, which will then improve upon the piezoelectric response.

Exploring Biomolecular Recognition by Modeling and Simulation

NASA Astrophysics Data System (ADS)

Wade, Rebecca

2007-12-01

Biomolecular recognition is complex. The balance between the different molecular properties that contribute to molecular recognition, such as shape, electrostatics, dynamics and entropy, varies from case to case. This, along with the extent of experimental characterization, influences the choice of appropriate computational approaches to study biomolecular interactions. I will present computational studies in which we aim to make concerted use of bioinformatics, biochemical network modeling and molecular simulation techniques to study protein-protein and protein-small molecule interactions and to facilitate computer-aided drug design.

Numerical evidence of liquid crystalline mesophases of a lollipop shaped model in two dimensions

NASA Astrophysics Data System (ADS)

Pérez-Lemus, G. R.; Armas-Pérez, J. C.; Chapela, G. A.; Quintana-H., J.

2017-12-01

Small alterations in the molecular details may produce noticeable changes in the symmetry of the resulting phase behavior. It is possible to produce morphologies having different n-fold symmetries by manipulating molecular features such as chirality, polarity or anisotropy. In this paper, a two dimensional hard molecular model is introduced to study the formation of liquid crystalline phases in low dimensionality. The model is similar to that reported by Julio C. Armas-Pérez and Jacqueline Quintana-H., Phys. Rev. E 83, 051709 (2011). The main difference is the lack of chirality in the model proposed, although they share some characteristics like the geometrical polarity. Our model is called a lollipop model, because its shape is constructed by a rounded section attached to the end of a stick. Contrary to what happens in three dimensions where chiral nematogens produce interesting and complex phases such as blue phases, the lack of molecular chirality of our model generates a richer phase diagram compared to the chiral system. We show numerical and some geometrical evidences that the lack of laterality of the non chiral model seems to provide more routes of molecular self-assembly, producing triatic, a random cluster and possibly a tetratic phase behavior which were not presented in the previous work. We support our conclusions using results obtained from isobaric and isochoric Monte Carlo simulations. Properties as the n-fold order parameters such as the nematic, tetratic and triatic as well as their correlation functions were used to characterize the phases. We also provide the Fourier transform of equilibrium configurations to analyze the n-fold symmetry characteristic of each phase.

Carbon chemistry in dense molecular clouds: Theory and observational constraints

NASA Technical Reports Server (NTRS)

Blake, Geoffrey A.

1990-01-01

For the most part, gas phase models of the chemistry of dense molecular clouds predict the abundances of simple species rather well. However, for larger molecules and even for small systems rich in carbon these models often fail spectacularly. Researchers present a brief review of the basic assumptions and results of large scale modeling of the carbon chemistry in dense molecular clouds. Particular attention is to the influence of the gas phase C/O ratio in molecular clouds, and the likely role grains play in maintaining this ratio as clouds evolve from initially diffuse objects to denser cores with associated stellar and planetary formation. Recent spectral line surveys at centimeter and millimeter wavelengths along with selected observations in the submillimeter have now produced an accurate inventory of the gas phase carbon budget in several different types of molecular clouds, though gaps in our knowledge clearly remain. The constraints these observations place on theoretical models of interstellar chemistry can be used to gain insights into why the models fail, and show also which neglected processes must be included in more complete analyses. Looking toward the future, larger molecules are especially difficult to study both experimentally and theoretically in such dense, cold regions, and some new methods are therefore outlined which may ultimately push the detectability of small carbon chains and rings to much heavier species.

Microbial production of polyhydroxybutyrate with tailor-made properties: an integrated modelling approach and experimental validation.

PubMed

Penloglou, Giannis; Chatzidoukas, Christos; Kiparissides, Costas

2012-01-01

The microbial production of polyhydroxybutyrate (PHB) is a complex process in which the final quantity and quality of the PHB depend on a large number of process operating variables. Consequently, the design and optimal dynamic operation of a microbial process for the efficient production of PHB with tailor-made molecular properties is an extremely interesting problem. The present study investigates how key process operating variables (i.e., nutritional and aeration conditions) affect the biomass production rate and the PHB accumulation in the cells and its associated molecular weight distribution. A combined metabolic/polymerization/macroscopic modelling approach, relating the process performance and product quality with the process variables, was developed and validated using an extensive series of experiments and measurements. The model predicts the dynamic evolution of the biomass growth, the polymer accumulation, the consumption of carbon and nitrogen sources and the average molecular weights of the PHB in a bioreactor, under batch and fed-batch operating conditions. The proposed integrated model was used for the model-based optimization of the production of PHB with tailor-made molecular properties in Azohydromonas lata bacteria. The process optimization led to a high intracellular PHB accumulation (up to 95% g of PHB per g of DCW) and the production of different grades (i.e., different molecular weight distributions) of PHB. Copyright © 2011 Elsevier Inc. All rights reserved.

Gradient Models in Molecular Biophysics: Progress, Challenges, Opportunities

PubMed Central

Bardhan, Jaydeep P.

2014-01-01

In the interest of developing a bridge between researchers modeling materials and those modeling biological molecules, we survey recent progress in developing nonlocal-dielectric continuum models for studying the behavior of proteins and nucleic acids. As in other areas of science, continuum models are essential tools when atomistic simulations (e.g. molecular dynamics) are too expensive. Because biological molecules are essentially all nanoscale systems, the standard continuum model, involving local dielectric response, has basically always been dubious at best. The advanced continuum theories discussed here aim to remedy these shortcomings by adding features such as nonlocal dielectric response, and nonlinearities resulting from dielectric saturation. We begin by describing the central role of electrostatic interactions in biology at the molecular scale, and motivate the development of computationally tractable continuum models using applications in science and engineering. For context, we highlight some of the most important challenges that remain and survey the diverse theoretical formalisms for their treatment, highlighting the rigorous statistical mechanics that support the use and improvement of continuum models. We then address the development and implementation of nonlocal dielectric models, an approach pioneered by Dogonadze, Kornyshev, and their collaborators almost forty years ago. The simplest of these models is just a scalar form of gradient elasticity, and here we use ideas from gradient-based modeling to extend the electrostatic model to include additional length scales. The paper concludes with a discussion of open questions for model development, highlighting the many opportunities for the materials community to leverage its physical, mathematical, and computational expertise to help solve one of the most challenging questions in molecular biology and biophysics. PMID:25505358

Gradient Models in Molecular Biophysics: Progress, Challenges, Opportunities.

PubMed

Bardhan, Jaydeep P

2013-12-01

In the interest of developing a bridge between researchers modeling materials and those modeling biological molecules, we survey recent progress in developing nonlocal-dielectric continuum models for studying the behavior of proteins and nucleic acids. As in other areas of science, continuum models are essential tools when atomistic simulations (e.g. molecular dynamics) are too expensive. Because biological molecules are essentially all nanoscale systems, the standard continuum model, involving local dielectric response, has basically always been dubious at best. The advanced continuum theories discussed here aim to remedy these shortcomings by adding features such as nonlocal dielectric response, and nonlinearities resulting from dielectric saturation. We begin by describing the central role of electrostatic interactions in biology at the molecular scale, and motivate the development of computationally tractable continuum models using applications in science and engineering. For context, we highlight some of the most important challenges that remain and survey the diverse theoretical formalisms for their treatment, highlighting the rigorous statistical mechanics that support the use and improvement of continuum models. We then address the development and implementation of nonlocal dielectric models, an approach pioneered by Dogonadze, Kornyshev, and their collaborators almost forty years ago. The simplest of these models is just a scalar form of gradient elasticity, and here we use ideas from gradient-based modeling to extend the electrostatic model to include additional length scales. The paper concludes with a discussion of open questions for model development, highlighting the many opportunities for the materials community to leverage its physical, mathematical, and computational expertise to help solve one of the most challenging questions in molecular biology and biophysics.

Gradient models in molecular biophysics: progress, challenges, opportunities

NASA Astrophysics Data System (ADS)

Bardhan, Jaydeep P.

2013-12-01

In the interest of developing a bridge between researchers modeling materials and those modeling biological molecules, we survey recent progress in developing nonlocal-dielectric continuum models for studying the behavior of proteins and nucleic acids. As in other areas of science, continuum models are essential tools when atomistic simulations (e.g., molecular dynamics) are too expensive. Because biological molecules are essentially all nanoscale systems, the standard continuum model, involving local dielectric response, has basically always been dubious at best. The advanced continuum theories discussed here aim to remedy these shortcomings by adding nonlocal dielectric response. We begin by describing the central role of electrostatic interactions in biology at the molecular scale, and motivate the development of computationally tractable continuum models using applications in science and engineering. For context, we highlight some of the most important challenges that remain, and survey the diverse theoretical formalisms for their treatment, highlighting the rigorous statistical mechanics that support the use and improvement of continuum models. We then address the development and implementation of nonlocal dielectric models, an approach pioneered by Dogonadze, Kornyshev, and their collaborators almost 40 years ago. The simplest of these models is just a scalar form of gradient elasticity, and here we use ideas from gradient-based modeling to extend the electrostatic model to include additional length scales. The review concludes with a discussion of open questions for model development, highlighting the many opportunities for the materials community to leverage its physical, mathematical, and computational expertise to help solve one of the most challenging questions in molecular biology and biophysics.

Discrete diffusion models to study the effects of Mg2+ concentration on the PhoPQ signal transduction system

PubMed Central

2010-01-01

Background The challenge today is to develop a modeling and simulation paradigm that integrates structural, molecular and genetic data for a quantitative understanding of physiology and behavior of biological processes at multiple scales. This modeling method requires techniques that maintain a reasonable accuracy of the biological process and also reduces the computational overhead. This objective motivates the use of new methods that can transform the problem from energy and affinity based modeling to information theory based modeling. To achieve this, we transform all dynamics within the cell into a random event time, which is specified through an information domain measure like probability distribution. This allows us to use the “in silico” stochastic event based modeling approach to find the molecular dynamics of the system. Results In this paper, we present the discrete event simulation concept using the example of the signal transduction cascade triggered by extra-cellular Mg2+ concentration in the two component PhoPQ regulatory system of Salmonella Typhimurium. We also present a model to compute the information domain measure of the molecular transport process by estimating the statistical parameters of inter-arrival time between molecules/ions coming to a cell receptor as external signal. This model transforms the diffusion process into the information theory measure of stochastic event completion time to get the distribution of the Mg2+ departure events. Using these molecular transport models, we next study the in-silico effects of this external trigger on the PhoPQ system. Conclusions Our results illustrate the accuracy of the proposed diffusion models in explaining the molecular/ionic transport processes inside the cell. Also, the proposed simulation framework can incorporate the stochasticity in cellular environments to a certain degree of accuracy. We expect that this scalable simulation platform will be able to model more complex biological systems with reasonable accuracy to understand their temporal dynamics. PMID:21143785

Discrete diffusion models to study the effects of Mg2+ concentration on the PhoPQ signal transduction system.

PubMed

Ghosh, Preetam; Ghosh, Samik; Basu, Kalyan; Das, Sajal K; Zhang, Chaoyang

2010-12-01

The challenge today is to develop a modeling and simulation paradigm that integrates structural, molecular and genetic data for a quantitative understanding of physiology and behavior of biological processes at multiple scales. This modeling method requires techniques that maintain a reasonable accuracy of the biological process and also reduces the computational overhead. This objective motivates the use of new methods that can transform the problem from energy and affinity based modeling to information theory based modeling. To achieve this, we transform all dynamics within the cell into a random event time, which is specified through an information domain measure like probability distribution. This allows us to use the "in silico" stochastic event based modeling approach to find the molecular dynamics of the system. In this paper, we present the discrete event simulation concept using the example of the signal transduction cascade triggered by extra-cellular Mg2+ concentration in the two component PhoPQ regulatory system of Salmonella Typhimurium. We also present a model to compute the information domain measure of the molecular transport process by estimating the statistical parameters of inter-arrival time between molecules/ions coming to a cell receptor as external signal. This model transforms the diffusion process into the information theory measure of stochastic event completion time to get the distribution of the Mg2+ departure events. Using these molecular transport models, we next study the in-silico effects of this external trigger on the PhoPQ system. Our results illustrate the accuracy of the proposed diffusion models in explaining the molecular/ionic transport processes inside the cell. Also, the proposed simulation framework can incorporate the stochasticity in cellular environments to a certain degree of accuracy. We expect that this scalable simulation platform will be able to model more complex biological systems with reasonable accuracy to understand their temporal dynamics.

Evaluating Force-Field London Dispersion Coefficients Using the Exchange-Hole Dipole Moment Model.

PubMed

Mohebifar, Mohamad; Johnson, Erin R; Rowley, Christopher N

2017-12-12

London dispersion interactions play an integral role in materials science and biophysics. Force fields for atomistic molecular simulations typically represent dispersion interactions by the 12-6 Lennard-Jones potential using empirically determined parameters. These parameters are generally underdetermined, and there is no straightforward way to test if they are physically realistic. Alternatively, the exchange-hole dipole moment (XDM) model from density-functional theory predicts atomic and molecular London dispersion coefficients from first principles, providing an innovative strategy to validate the dispersion terms of molecular-mechanical force fields. In this work, the XDM model was used to obtain the London dispersion coefficients of 88 organic molecules relevant to biochemistry and pharmaceutical chemistry and the values compared with those derived from the Lennard-Jones parameters of the CGenFF, GAFF, OPLS, and Drude polarizable force fields. The molecular dispersion coefficients for the CGenFF, GAFF, and OPLS models are systematically higher than the XDM-calculated values by a factor of roughly 1.5, likely due to neglect of higher order dispersion terms and premature truncation of the dispersion-energy summation. The XDM dispersion coefficients span a large range for some molecular-mechanical atom types, suggesting an unrecognized source of error in force-field models, which assume that atoms of the same type have the same dispersion interactions. Agreement with the XDM dispersion coefficients is even poorer for the Drude polarizable force field. Popular water models were also examined, and TIP3P was found to have dispersion coefficients similar to the experimental and XDM references, although other models employ anomalously high values. Finally, XDM-derived dispersion coefficients were used to parametrize molecular-mechanical force fields for five liquids-benzene, toluene, cyclohexane, n-pentane, and n-hexane-which resulted in improved accuracy in the computed enthalpies of vaporization despite only having to evaluate a much smaller section of the parameter space.

Temperature effects on multiphase reactions of organic molecular markers: A modeling study

NASA Astrophysics Data System (ADS)

Pratap, Vikram; Chen, Ying; Yao, Guangming; Nakao, Shunsuke

2018-04-01

Various molecular markers are used in source apportionment studies. In early studies, molecular markers were assumed to be inert. However, recent studies suggest that molecular markers can decay rapidly through multiphase reactions, which makes interpretation of marker measurements challenging. This study presents a simplified model to account for the effects of temperature and relative humidity on the lifetime of molecular markers through a shift in gas-particle partitioning as well as a change in viscosity of the condensed phase. As a model case, this study examines the stability of levoglucosan, a key marker species of biomass burning, over a wide temperature range relevant to summertime and wintertime. Despite the importance of wood combustion for space heating in winter, the lifetime of levoglucosan in wintertime is not well understood. The model predicts that in low-temperature conditions, levoglucosan predominantly remains in the particle phase, and therefore its loss due to gas-phase oxidation reactions is significantly reduced. Furthermore, the movement of the levoglucosan from the bulk of the particle to the particle surface is reduced due to low diffusivity in the semi-solid state. The simplified model developed in this study reasonably reproduces upper and lower bounds of the lifetime of levoglucosan investigated in previous studies. The model results show that the levoglucosan depletion after seven days reduces significantly from ∼98% at 25 °C to <1% at 0 °C under dry conditions. The depletion of levoglucosan increases at higher relative humidities. However, at temperatures below 0 °C, levoglucosan appears to be a useful marker (lifetime > 1 week) even at 60% relative humidity irrespective of the assumed fragility parameter D that controls estimated diffusivity. The model shows that lifetime of an organic molecular marker strongly depends on assumed D especially when a semi-volatile marker is in semi-solid organic aerosol.

Visualizing functional motions of membrane transporters with molecular dynamics simulations.

PubMed

Shaikh, Saher A; Li, Jing; Enkavi, Giray; Wen, Po-Chao; Huang, Zhijian; Tajkhorshid, Emad

2013-01-29

Computational modeling and molecular simulation techniques have become an integral part of modern molecular research. Various areas of molecular sciences continue to benefit from, indeed rely on, the unparalleled spatial and temporal resolutions offered by these technologies, to provide a more complete picture of the molecular problems at hand. Because of the continuous development of more efficient algorithms harvesting ever-expanding computational resources, and the emergence of more advanced and novel theories and methodologies, the scope of computational studies has expanded significantly over the past decade, now including much larger molecular systems and far more complex molecular phenomena. Among the various computer modeling techniques, the application of molecular dynamics (MD) simulation and related techniques has particularly drawn attention in biomolecular research, because of the ability of the method to describe the dynamical nature of the molecular systems and thereby to provide a more realistic representation, which is often needed for understanding fundamental molecular properties. The method has proven to be remarkably successful in capturing molecular events and structural transitions highly relevant to the function and/or physicochemical properties of biomolecular systems. Herein, after a brief introduction to the method of MD, we use a number of membrane transport proteins studied in our laboratory as examples to showcase the scope and applicability of the method and its power in characterizing molecular motions of various magnitudes and time scales that are involved in the function of this important class of membrane proteins.

Visualizing Functional Motions of Membrane Transporters with Molecular Dynamics Simulations

PubMed Central

2013-01-01

Computational modeling and molecular simulation techniques have become an integral part of modern molecular research. Various areas of molecular sciences continue to benefit from, indeed rely on, the unparalleled spatial and temporal resolutions offered by these technologies, to provide a more complete picture of the molecular problems at hand. Because of the continuous development of more efficient algorithms harvesting ever-expanding computational resources, and the emergence of more advanced and novel theories and methodologies, the scope of computational studies has expanded significantly over the past decade, now including much larger molecular systems and far more complex molecular phenomena. Among the various computer modeling techniques, the application of molecular dynamics (MD) simulation and related techniques has particularly drawn attention in biomolecular research, because of the ability of the method to describe the dynamical nature of the molecular systems and thereby to provide a more realistic representation, which is often needed for understanding fundamental molecular properties. The method has proven to be remarkably successful in capturing molecular events and structural transitions highly relevant to the function and/or physicochemical properties of biomolecular systems. Herein, after a brief introduction to the method of MD, we use a number of membrane transport proteins studied in our laboratory as examples to showcase the scope and applicability of the method and its power in characterizing molecular motions of various magnitudes and time scales that are involved in the function of this important class of membrane proteins. PMID:23298176

Students' use of atomic and molecular models in learning chemistry

NASA Astrophysics Data System (ADS)

O'Connor, Eileen Ann

1997-09-01

The objective of this study was to investigate the development of introductory college chemistry students' use of atomic and molecular models to explain physical and chemical phenomena. The study was conducted during the first semester of the course at a University and College II. Public institution (Carnegie Commission of Higher Education, 1973). Students' use of models was observed during one-on-one interviews conducted over the course of the semester. The approach to introductory chemistry emphasized models. Students were exposed to over two-hundred and fifty atomic and molecular models during lectures, were assigned text readings that used over a thousand models, and worked interactively with dozens of models on the computer. These models illustrated various features of the spatial organization of valence electrons and nuclei in atoms and molecules. Despite extensive exposure to models in lectures, in textbook, and in computer-based activities, the students in the study based their explanation in large part on a simple Bohr model (electrons arranged in concentric circles around the nuclei)--a model that had not been introduced in the course. Students used visual information from their models to construct their explanation, while overlooking inter-atomic and intra-molecular forces which are not represented explicitly in the models. In addition, students often explained phenomena by adding separate information about the topic without either integrating or logically relating this information into a cohesive explanation. The results of the study demonstrate that despite the extensive use of models in chemistry instruction, students do not necessarily apply them appropriately in explaining chemical and physical phenomena. The results of this study suggest that for the power of models as aids to learning to be more fully realized, chemistry professors must give more attention to the selection, use, integration, and limitations of models in their instruction.

Evolution and development of model membranes for physicochemical and functional studies of the membrane lateral heterogeneity.

PubMed

Morigaki, Kenichi; Tanimoto, Yasushi

2018-03-14

One of the main questions in the membrane biology is the functional roles of membrane heterogeneity and molecular localization. Although segregation and local enrichment of protein/lipid components (rafts) have been extensively studied, the presence and functions of such membrane domains still remain elusive. Along with biochemical, cell observation, and simulation studies, model membranes are emerging as an important tool for understanding the biological membrane, providing quantitative information on the physicochemical properties of membrane proteins and lipids. Segregation of fluid lipid bilayer into liquid-ordered (Lo) and liquid-disordered (Ld) phases has been studied as a simplified model of raft in model membranes, including giant unilamellar vesicles (GUVs), giant plasma membrane vesicles (GPMVs), and supported lipid bilayers (SLB). Partition coefficients of membrane proteins between Lo and Ld phases were measured to gauze their affinities to lipid rafts (raftophilicity). One important development in model membrane is patterned SLB based on the microfabrication technology. Patterned Lo/Ld phases have been applied to study the partition and function of membrane-bound molecules. Quantitative information of individual molecular species attained by model membranes is critical for elucidating the molecular functions in the complex web of molecular interactions. The present review gives a short account of the model membranes developed for studying the lateral heterogeneity, especially focusing on patterned model membranes on solid substrates. Copyright © 2018 Elsevier B.V. All rights reserved.

Photoelectron angular distributions for states of any mixed character: An experiment-friendly model for atomic, molecular, and cluster anions

NASA Astrophysics Data System (ADS)

Khuseynov, Dmitry; Blackstone, Christopher C.; Culberson, Lori M.; Sanov, Andrei

2014-09-01

We present a model for laboratory-frame photoelectron angular distributions in direct photodetachment from (in principle) any molecular orbital using linearly polarized light. A transparent mathematical approach is used to generalize the Cooper-Zare central-potential model to anionic states of any mixed character. In the limit of atomic-anion photodetachment, the model reproduces the Cooper-Zare formula. In the case of an initial orbital described as a superposition of s and p-type functions, the model yields the previously obtained s-p mixing formula. The formalism is further advanced using the Hanstorp approximation, whereas the relative scaling of the partial-wave cross-sections is assumed to follow the Wigner threshold law. The resulting model describes the energy dependence of photoelectron anisotropy for any atomic, molecular, or cluster anions, usually without requiring a direct calculation of the transition dipole matrix elements. As a benchmark case, we apply the p-d variant of the model to the experimental results for NO- photodetachment and show that the observed anisotropy trend is described well using physically meaningful values of the model parameters. Overall, the presented formalism delivers insight into the photodetachment process and affords a new quantitative strategy for analyzing the photoelectron angular distributions and characterizing mixed-character molecular orbitals using photoelectron imaging spectroscopy of negative ions.

Photoelectron angular distributions for states of any mixed character: an experiment-friendly model for atomic, molecular, and cluster anions.

PubMed

Khuseynov, Dmitry; Blackstone, Christopher C; Culberson, Lori M; Sanov, Andrei

2014-09-28

We present a model for laboratory-frame photoelectron angular distributions in direct photodetachment from (in principle) any molecular orbital using linearly polarized light. A transparent mathematical approach is used to generalize the Cooper-Zare central-potential model to anionic states of any mixed character. In the limit of atomic-anion photodetachment, the model reproduces the Cooper-Zare formula. In the case of an initial orbital described as a superposition of s and p-type functions, the model yields the previously obtained s-p mixing formula. The formalism is further advanced using the Hanstorp approximation, whereas the relative scaling of the partial-wave cross-sections is assumed to follow the Wigner threshold law. The resulting model describes the energy dependence of photoelectron anisotropy for any atomic, molecular, or cluster anions, usually without requiring a direct calculation of the transition dipole matrix elements. As a benchmark case, we apply the p-d variant of the model to the experimental results for NO(-) photodetachment and show that the observed anisotropy trend is described well using physically meaningful values of the model parameters. Overall, the presented formalism delivers insight into the photodetachment process and affords a new quantitative strategy for analyzing the photoelectron angular distributions and characterizing mixed-character molecular orbitals using photoelectron imaging spectroscopy of negative ions.

Discovery of novel inhibitors of Mycobacterium tuberculosis MurG: homology modelling, structure based pharmacophore, molecular docking, and molecular dynamics simulations.

PubMed

Saxena, Shalini; Abdullah, Maaged; Sriram, Dharmarajan; Guruprasad, Lalitha

2017-10-17

MurG (Rv2153c) is a key player in the biosynthesis of the peptidoglycan layer in Mycobacterium tuberculosis (Mtb). This work is an attempt to highlight the structural and functional relationship of Mtb MurG, the three-dimensional (3D) structure of protein was constructed by homology modelling using Discovery Studio 3.5 software. The quality and consistency of generated model was assessed by PROCHECK, ProSA and ERRAT. Later, the model was optimized by molecular dynamics (MD) simulations and the optimized model complex with substrate Uridine-diphosphate-N-acetylglucosamine (UD1) facilitated us to employ structure-based virtual screening approach to obtain new hits from Asinex database using energy-optimized pharmacophore modelling (e-pharmacophore). The pharmacophore model was validated using enrichment calculations, and finally, validated model was employed for high-throughput virtual screening and molecular docking to identify novel Mtb MurG inhibitors. This study led to the identification of 10 potential compounds with good fitness, docking score, which make important interactions with the protein active site. The 25 ns MD simulations of three potential lead compounds with protein confirmed that the structure was stable and make several non-bonding interactions with amino acids, such as Leu290, Met310 and Asn167. Hence, we concluded that the identified compounds may act as new leads for the design of Mtb MurG inhibitors.

Modelling dishes and exploring culinary 'precisions': the two issues of molecular gastronomy.

PubMed

This, Hervé

2005-04-01

The scientific strategy of molecular gastronomy includes modelling 'culinary definitions' and experimental explorations of 'culinary precisions'. A formalism that describes complex dispersed systems leads to a physical classification of classical sauces, as well as to the invention of an infinite number of new dishes.

The Use of Molecular Modeling Programs in Medicinal Chemistry Instruction.

ERIC Educational Resources Information Center

Harrold, Marc W.

1992-01-01

This paper describes and evaluates the use of a molecular modeling computer program (Alchemy II) in a pharmaceutical education program. Provided are the hardware requirements and basic program features as well as several examples of how this program and its features have been applied in the classroom. (GLR)

Preliminary Modulus and Breakage Calculations on Cellulose Models

USDA-ARS?s Scientific Manuscript database

The Young’s modulus of polymers can be calculated by stretching molecular models with the computer. The molecule is stretched and the derivative of the changes in stored potential energy for several displacements, divided by the molecular cross-section area, is the stress. The modulus is the slope o...

Do Haptic Representations Help Complex Molecular Learning?

ERIC Educational Resources Information Center

Bivall, Petter; Ainsworth, Shaaron; Tibell, Lena A. E.

2011-01-01

This study explored whether adding a haptic interface (that provides users with somatosensory information about virtual objects by force and tactile feedback) to a three-dimensional (3D) chemical model enhanced students' understanding of complex molecular interactions. Two modes of the model were compared in a between-groups pre- and posttest…

Molecular Dynamics Modeling and Simulation of Diamond Cutting of Cerium.

PubMed

Zhang, Junjie; Zheng, Haibing; Shuai, Maobing; Li, Yao; Yang, Yang; Sun, Tao

2017-12-01

The coupling between structural phase transformations and dislocations induces challenges in understanding the deformation behavior of metallic cerium at the nanoscale. In the present work, we elucidate the underlying mechanism of cerium under ultra-precision diamond cutting by means of molecular dynamics modeling and simulations. The molecular dynamics model of diamond cutting of cerium is established by assigning empirical potentials to describe atomic interactions and evaluating properties of two face-centered cubic cerium phases. Subsequent molecular dynamics simulations reveal that dislocation slip dominates the plastic deformation of cerium under the cutting process. In addition, the analysis based on atomic radial distribution functions demonstrates that there are trivial phase transformations from the γ-Ce to the δ-Ce occurred in both machined surface and formed chip. Following investigations on machining parameter dependence reveal the optimal machining conditions for achieving high quality of machined surface of cerium.

Molecular Dynamics Modeling and Simulation of Diamond Cutting of Cerium

NASA Astrophysics Data System (ADS)

Zhang, Junjie; Zheng, Haibing; Shuai, Maobing; Li, Yao; Yang, Yang; Sun, Tao

2017-07-01

The coupling between structural phase transformations and dislocations induces challenges in understanding the deformation behavior of metallic cerium at the nanoscale. In the present work, we elucidate the underlying mechanism of cerium under ultra-precision diamond cutting by means of molecular dynamics modeling and simulations. The molecular dynamics model of diamond cutting of cerium is established by assigning empirical potentials to describe atomic interactions and evaluating properties of two face-centered cubic cerium phases. Subsequent molecular dynamics simulations reveal that dislocation slip dominates the plastic deformation of cerium under the cutting process. In addition, the analysis based on atomic radial distribution functions demonstrates that there are trivial phase transformations from the γ-Ce to the δ-Ce occurred in both machined surface and formed chip. Following investigations on machining parameter dependence reveal the optimal machining conditions for achieving high quality of machined surface of cerium.

A Langevin model for fluctuating contact angle behaviour parametrised using molecular dynamics.

PubMed

Smith, E R; Müller, E A; Craster, R V; Matar, O K

2016-12-06

Molecular dynamics simulations are employed to develop a theoretical model to predict the fluid-solid contact angle as a function of wall-sliding speed incorporating thermal fluctuations. A liquid bridge between counter-sliding walls is studied, with liquid-vapour interface-tracking, to explore the impact of wall-sliding speed on contact angle. The behaviour of the macroscopic contact angle varies linearly over a range of capillary numbers beyond which the liquid bridge pinches off, a behaviour supported by experimental results. Nonetheless, the liquid bridge provides an ideal test case to study molecular scale thermal fluctuations, which are shown to be well described by Gaussian distributions. A Langevin model for contact angle is parametrised to incorporate the mean, fluctuation and auto-correlations over a range of sliding speeds and temperatures. The resulting equations can be used as a proxy for the fully-detailed molecular dynamics simulation allowing them to be integrated within a continuum-scale solver.

Development and validation of risk models and molecular diagnostics to permit personalized management of cancer.

PubMed

Pu, Xia; Ye, Yuanqing; Wu, Xifeng

2014-01-01

Despite the advances made in cancer management over the past few decades, improvements in cancer diagnosis and prognosis are still poor, highlighting the need for individualized strategies. Toward this goal, risk prediction models and molecular diagnostic tools have been developed, tailoring each step of risk assessment from diagnosis to treatment and clinical outcomes based on the individual's clinical, epidemiological, and molecular profiles. These approaches hold increasing promise for delivering a new paradigm to maximize the efficiency of cancer surveillance and efficacy of treatment. However, they require stringent study design, methodology development, comprehensive assessment of biomarkers and risk factors, and extensive validation to ensure their overall usefulness for clinical translation. In the current study, the authors conducted a systematic review using breast cancer as an example and provide general guidelines for risk prediction models and molecular diagnostic tools, including development, assessment, and validation. © 2013 American Cancer Society.

Molecular dynamics simulations of theoretical cellulose nanotube models.

PubMed

Uto, Takuya; Kodama, Yuta; Miyata, Tatsuhiko; Yui, Toshifumi

2018-06-15

Nanotubes are remarkable nanoscale architectures for a wide range of potential applications. In the present paper, we report a molecular dynamics (MD) study of the theoretical cellulose nanotube (CelNT) models to evaluate their dynamic behavior in solution (either chloroform or benzene). Based on the one-quarter chain staggering relationship, we constructed six CelNT models by combining the two chain polarities (parallel (P) and antiparallel (AP)) and three symmetry operations (helical right (H R ), helical left (H L ), and rotation (R)) to generate a circular arrangement of molecular chains. Among the four models that retained the tubular form (P-H R , P-H L , P-R, and AP-R), the P-R and AP-R models have the lowest steric energies in benzene and chloroform, respectively. The structural features of the CelNT models were characterized in terms of the hydroxymethyl group conformation and intermolecular hydrogen bonds. Solvent structuring more clearly occurred with benzene than chloroform, suggesting that the CelNT models may disperse in benzene. Copyright © 2018 Elsevier Ltd. All rights reserved.

State-space reduction and equivalence class sampling for a molecular self-assembly model.

PubMed

Packwood, Daniel M; Han, Patrick; Hitosugi, Taro

2016-07-01

Direct simulation of a model with a large state space will generate enormous volumes of data, much of which is not relevant to the questions under study. In this paper, we consider a molecular self-assembly model as a typical example of a large state-space model, and present a method for selectively retrieving 'target information' from this model. This method partitions the state space into equivalence classes, as identified by an appropriate equivalence relation. The set of equivalence classes H, which serves as a reduced state space, contains none of the superfluous information of the original model. After construction and characterization of a Markov chain with state space H, the target information is efficiently retrieved via Markov chain Monte Carlo sampling. This approach represents a new breed of simulation techniques which are highly optimized for studying molecular self-assembly and, moreover, serves as a valuable guideline for analysis of other large state-space models.

Molecular Diagnostics of Supernova Remnant Shocks

NASA Astrophysics Data System (ADS)

Lazendic, J. S.; Wardle, M.; Green, A. J.; Whiteoak, J. B.; Burton, M. G.

We have undertaken a study of radio and infrared molecular-line emission towards several SNRs in order to investigate molecular signatures of SNR shocks, and to test models for OH maser production in SNRs. Here we present results on G349.7+0.2.

Molecular simulations of self-assembly processes in metal-organic frameworks: Model dependence

NASA Astrophysics Data System (ADS)

Biswal, Debasmita; Kusalik, Peter G.

2017-07-01

Molecular simulation is a powerful tool for investigating microscopic behavior in various chemical systems, where the use of suitable models is critical to successfully reproduce the structural and dynamic properties of the real systems of interest. In this context, molecular dynamics simulation studies of self-assembly processes in metal-organic frameworks (MOFs), a well-known class of porous materials with interesting chemical and physical properties, are relatively challenging, where a reasonably accurate representation of metal-ligand interactions is anticipated to play an important role. In the current study, we both investigate the performance of some existing models and introduce and test new models to help explore the self-assembly in an archetypal Zn-carboxylate MOF system. To this end, the behavior of six different Zn-ion models, three solvent models, and two ligand models was examined and validated against key experimental structural parameters. To explore longer time scale ordering events during MOF self-assembly via explicit solvent simulations, it is necessary to identify a suitable combination of simplified model components representing metal ions, organic ligands, and solvent molecules. It was observed that an extended cationic dummy atom (ECDA) Zn-ion model combined with an all-atom carboxylate ligand model and a simple dipolar solvent model can reproduce characteristic experimental structures for the archetypal MOF system. The successful use of these models in extensive sets of molecular simulations, which provide key insights into the self-assembly mechanism of this archetypal MOF system occurring during the early stages of this process, has been very recently reported.

Coupling discrete and continuum concentration particle models for multiscale and hybrid molecular-continuum simulations

DOE PAGES

Petsev, Nikolai Dimitrov; Leal, L. Gary; Shell, M. Scott

2017-12-21

Hybrid molecular-continuum simulation techniques afford a number of advantages for problems in the rapidly burgeoning area of nanoscale engineering and technology, though they are typically quite complex to implement and limited to single-component fluid systems. We describe an approach for modeling multicomponent hydrodynamic problems spanning multiple length scales when using particle-based descriptions for both the finely-resolved (e.g. molecular dynamics) and coarse-grained (e.g. continuum) subregions within an overall simulation domain. This technique is based on the multiscale methodology previously developed for mesoscale binary fluids [N. D. Petsev, L. G. Leal, and M. S. Shell, J. Chem. Phys. 144, 84115 (2016)], simulatedmore » using a particle-based continuum method known as smoothed dissipative particle dynamics (SDPD). An important application of this approach is the ability to perform coupled molecular dynamics (MD) and continuum modeling of molecularly miscible binary mixtures. In order to validate this technique, we investigate multicomponent hybrid MD-continuum simulations at equilibrium, as well as non-equilibrium cases featuring concentration gradients.« less

Anticipatory dynamics of biological systems: from molecular quantum states to evolution

NASA Astrophysics Data System (ADS)

Igamberdiev, Abir U.

2015-08-01

Living systems possess anticipatory behaviour that is based on the flexibility of internal models generated by the system's embedded description. The idea was suggested by Aristotle and is explicitly introduced to theoretical biology by Rosen. The possibility of holding the embedded internal model is grounded in the principle of stable non-equilibrium (Bauer). From the quantum mechanical view, this principle aims to minimize energy dissipation in expense of long relaxation times. The ideas of stable non-equilibrium were developed by Liberman who viewed living systems as subdivided into the quantum regulator and the molecular computer supporting coherence of the regulator's internal quantum state. The computational power of the cell molecular computer is based on the possibility of molecular rearrangements according to molecular addresses. In evolution, the anticipatory strategies are realized both as a precession of phylogenesis by ontogenesis (Berg) and as the anticipatory search of genetic fixation of adaptive changes that incorporates them into the internal model of genetic system. We discuss how the fundamental ideas of anticipation can be introduced into the basic foundations of theoretical biology.

Coupling discrete and continuum concentration particle models for multiscale and hybrid molecular-continuum simulations

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

Petsev, Nikolai Dimitrov; Leal, L. Gary; Shell, M. Scott

Hybrid molecular-continuum simulation techniques afford a number of advantages for problems in the rapidly burgeoning area of nanoscale engineering and technology, though they are typically quite complex to implement and limited to single-component fluid systems. We describe an approach for modeling multicomponent hydrodynamic problems spanning multiple length scales when using particle-based descriptions for both the finely-resolved (e.g. molecular dynamics) and coarse-grained (e.g. continuum) subregions within an overall simulation domain. This technique is based on the multiscale methodology previously developed for mesoscale binary fluids [N. D. Petsev, L. G. Leal, and M. S. Shell, J. Chem. Phys. 144, 84115 (2016)], simulatedmore » using a particle-based continuum method known as smoothed dissipative particle dynamics (SDPD). An important application of this approach is the ability to perform coupled molecular dynamics (MD) and continuum modeling of molecularly miscible binary mixtures. In order to validate this technique, we investigate multicomponent hybrid MD-continuum simulations at equilibrium, as well as non-equilibrium cases featuring concentration gradients.« less

Bond-valence methods for pKa prediction. II. Bond-valence, electrostatic, molecular geometry, and solvation effects

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

Bickmore, Barry R.; Rosso, Kevin M.; Tadanier, Christopher J.

2006-08-15

In a previous contribution, we outlined a method for predicting (hydr)oxy-acid and oxide surface acidity constants based on three main factors: bond valence, Me?O bond ionicity, and molecular shape. Here electrostatics calculations and ab initio molecular dynamics simulations are used to qualitatively show that Me?O bond ionicity controls the extent to which the electrostatic work of proton removal departs from ideality, bond valence controls the extent of solvation of individual functional groups, and bond valence and molecular shape controls local dielectric response. These results are consistent with our model of acidity, but completely at odds with other methods of predictingmore » acidity constants for use in multisite complexation models. In particular, our ab initio molecular dynamics simulations of solvated monomers clearly indicate that hydrogen bonding between (hydr)oxo-groups and water molecules adjusts to obey the valence sum rule, rather than maintaining a fixed valence based on the coordination of the oxygen atom as predicted by the standard MUSIC model.« less

Modelling Molecular Mechanisms: A Framework of Scientific Reasoning to Construct Molecular-Level Explanations for Cellular Behaviour

ERIC Educational Resources Information Center

van Mil, Marc H. W.; Boerwinkel, Dirk Jan; Waarlo, Arend Jan

2013-01-01

Although molecular-level details are part of the upper-secondary biology curriculum in most countries, many studies report that students fail to connect molecular knowledge to phenomena at the level of cells, organs and organisms. Recent studies suggest that students lack a framework to reason about complex systems to make this connection. In this…

Accelerating the Use of Molecular Modeling in the High School Classroom with VMD Lite

ERIC Educational Resources Information Center

Lundquist, Karl; Herndon, Conner; Harty, Tyson H.; Gumbart, James C.

2016-01-01

It is often difficult for students to develop an intuition about molecular processes, which occur in a realm far different from day-to-day life. For example, thermal fluctuations take on hurricane-like proportions at the molecular scale. Students need a way to visualize realistic depictions of molecular processes to appreciate them. To this end,…

Modeling Contamination Migration on the Chandra X-ray Observatory II

NASA Technical Reports Server (NTRS)

O'Dell, Steve; Swartz, Doug; Tice, Neil; Plucinsky, Paul; Grant, Catherine; Marshall, Herman; Vikhlinin, Alexey

2013-01-01

During its first 14 years of operation, the cold (about -60degC) optical blocking filter of the Advanced CCD Imaging Spectrometer (ACIS), aboard the Chandra X-ray Observatory, has accumulated a growing layer of molecular contamination that attenuates low-energy x rays. Over the past few years, the accumulation rate, spatial distribution, and composition may have changed, perhaps partially related to changes in the operating temperature of the ACIS housing. This evolution of the accumulation of the molecular contamination has motivated further analysis of contamination migration on the Chandra X-ray Observatory, particularly within and near the ACIS cavity. To this end, the current study employs a higher-fidelity geometric model of the ACIS cavity, detailed thermal modeling based upon monitored temperature data, and an accordingly refined model of the molecular transport.

Assessing the accuracy of improved force-matched water models derived from Ab initio molecular dynamics simulations.

PubMed

Köster, Andreas; Spura, Thomas; Rutkai, Gábor; Kessler, Jan; Wiebeler, Hendrik; Vrabec, Jadran; Kühne, Thomas D

2016-07-15

The accuracy of water models derived from ab initio molecular dynamics simulations by means on an improved force-matching scheme is assessed for various thermodynamic, transport, and structural properties. It is found that although the resulting force-matched water models are typically less accurate than fully empirical force fields in predicting thermodynamic properties, they are nevertheless much more accurate than generally appreciated in reproducing the structure of liquid water and in fact superseding most of the commonly used empirical water models. This development demonstrates the feasibility to routinely parametrize computationally efficient yet predictive potential energy functions based on accurate ab initio molecular dynamics simulations for a large variety of different systems. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

A model of early formation of uranium molecular oxides in laser-ablated plasmas

NASA Astrophysics Data System (ADS)

Finko, Mikhail S.; Curreli, Davide; Weisz, David G.; Crowhurst, Jonathan C.; Rose, Timothy P.; Koroglu, Batikan; Radousky, Harry B.; Armstrong, Michael R.

2017-12-01

In this work, we present a newly constructed U x O y reaction mechanism that consists of 30 reaction channels (21 of which are reversible channels) for 11 uranium molecular species (including ions). Both the selection of reaction channels and calculation of corresponding rate coefficients is accomplished via a comprehensive literature review and application of basic reaction rate theory. The reaction mechanism is supplemented by a detailed description of oxygen plasma chemistry (19 species and 142 reaction channels) and is used to model an atmospheric laser ablated uranium plume via a 0D (global) model. The global model is used to analyze the evolution of key uranium molecular species predicted by the reaction mechanism, and the initial stage of formation of uranium oxide species.

Modeling and Deorphanization of Orphan GPCRs.

PubMed

Diaz, Constantino; Angelloz-Nicoud, Patricia; Pihan, Emilie

2018-01-01

Despite tremendous efforts, approximately 120 GPCRs remain orphan. Their physiological functions and their potential roles in diseases are poorly understood. Orphan GPCRs are extremely important because they may provide novel therapeutic targets for unmet medical needs. As a complement to experimental approaches, molecular modeling and virtual screening are efficient techniques to discover synthetic surrogate ligands which can help to elucidate the role of oGPCRs. Constitutively activated mutants and recently published active structures of GPCRs provide stimulating opportunities for building active molecular models for oGPCRs and identifying activators using virtual screening of compound libraries. We describe the molecular modeling and virtual screening process we have applied in the discovery of surrogate ligands, and provide examples for CCKA, a simulated oGPCR, and for two oGPCRs, GPR52 and GPR34.

Moving Contact Lines: Linking Molecular Dynamics and Continuum-Scale Modeling.

PubMed

Smith, Edward R; Theodorakis, Panagiotis E; Craster, Richard V; Matar, Omar K

2018-05-17

Despite decades of research, the modeling of moving contact lines has remained a formidable challenge in fluid dynamics whose resolution will impact numerous industrial, biological, and daily life applications. On the one hand, molecular dynamics (MD) simulation has the ability to provide unique insight into the microscopic details that determine the dynamic behavior of the contact line, which is not possible with either continuum-scale simulations or experiments. On the other hand, continuum-based models provide a link to the macroscopic description of the system. In this Feature Article, we explore the complex range of physical factors, including the presence of surfactants, which governs the contact line motion through MD simulations. We also discuss links between continuum- and molecular-scale modeling and highlight the opportunities for future developments in this area.

Advances and challenges in logical modeling of cell cycle regulation: perspective for multi-scale, integrative yeast cell models

PubMed Central

Todd, Robert G.; van der Zee, Lucas

2016-01-01

Abstract The eukaryotic cell cycle is robustly designed, with interacting molecules organized within a definite topology that ensures temporal precision of its phase transitions. Its underlying dynamics are regulated by molecular switches, for which remarkable insights have been provided by genetic and molecular biology efforts. In a number of cases, this information has been made predictive, through computational models. These models have allowed for the identification of novel molecular mechanisms, later validated experimentally. Logical modeling represents one of the youngest approaches to address cell cycle regulation. We summarize the advances that this type of modeling has achieved to reproduce and predict cell cycle dynamics. Furthermore, we present the challenge that this type of modeling is now ready to tackle: its integration with intracellular networks, and its formalisms, to understand crosstalks underlying systems level properties, ultimate aim of multi-scale models. Specifically, we discuss and illustrate how such an integration may be realized, by integrating a minimal logical model of the cell cycle with a metabolic network. PMID:27993914

The chemistry side of AOP: implications for toxicity ...

EPA Pesticide Factsheets

An adverse outcome pathway (AOP) is a structured representation of the biological events that lead to adverse impacts following a molecular initiating event caused by chemical interaction with a macromolecule. AOPs have been proposed to facilitate toxicity extrapolation across species through understanding of species similarity in the sequence of molecular, cellular, organ and organismal level responses. However, AOPs are non-specific regarding the identity of the chemical initiators, and the range of structures for which an AOP is considered applicable has generally been poorly defined. Applicability domain has been widely understood in the field of QSAR as the response and chemical structure space in which the model makes predictions with a given reliability, and has been traditionally applied to define the similarity of query molecules within the training set. Three dimensional (3D) receptor modeling offers an approach to better define the applicability domain for selected AOPs through determination of the chemical space of the molecular initiating event. Universal 3D-QSAR models were developed for acetylcholinesterase inhibitors and estrogen receptor agonists and antagonists using a combination of fingerprint, molecular docking and structure-based pharmacophore approaches. The models were based on the critical molecular interactions within each receptor ligand binding domain, and included the key amino acid residues responsible for high binding affinity. T

Structural Refinement of Proteins by Restrained Molecular Dynamics Simulations with Non-interacting Molecular Fragments.

PubMed

Shen, Rong; Han, Wei; Fiorin, Giacomo; Islam, Shahidul M; Schulten, Klaus; Roux, Benoît

2015-10-01

The knowledge of multiple conformational states is a prerequisite to understand the function of membrane transport proteins. Unfortunately, the determination of detailed atomic structures for all these functionally important conformational states with conventional high-resolution approaches is often difficult and unsuccessful. In some cases, biophysical and biochemical approaches can provide important complementary structural information that can be exploited with the help of advanced computational methods to derive structural models of specific conformational states. In particular, functional and spectroscopic measurements in combination with site-directed mutations constitute one important source of information to obtain these mixed-resolution structural models. A very common problem with this strategy, however, is the difficulty to simultaneously integrate all the information from multiple independent experiments involving different mutations or chemical labels to derive a unique structural model consistent with the data. To resolve this issue, a novel restrained molecular dynamics structural refinement method is developed to simultaneously incorporate multiple experimentally determined constraints (e.g., engineered metal bridges or spin-labels), each treated as an individual molecular fragment with all atomic details. The internal structure of each of the molecular fragments is treated realistically, while there is no interaction between different molecular fragments to avoid unphysical steric clashes. The information from all the molecular fragments is exploited simultaneously to constrain the backbone to refine a three-dimensional model of the conformational state of the protein. The method is illustrated by refining the structure of the voltage-sensing domain (VSD) of the Kv1.2 potassium channel in the resting state and by exploring the distance histograms between spin-labels attached to T4 lysozyme. The resulting VSD structures are in good agreement with the consensus model of the resting state VSD and the spin-spin distance histograms from ESR/DEER experiments on T4 lysozyme are accurately reproduced.

Constructing a molecular theory of self-assembly: Interplay of ideas from surfactants and block copolymers.

PubMed

Nagarajan, Ramanathan

2017-06-01

Low molecular weight surfactants and high molecular weight block copolymers display analogous self-assembly behavior in solutions and at interfaces, generating nanoscale structures of different shapes. Understanding the link between the molecular structure of these amphiphiles and their self-assembly behavior has been the goal of theoretical studies. Despite the analogies between surfactants and block copolymers, models predicting their self-assembly behavior have evolved independent of one another, each overlooking the molecular feature considered critical to the other. In this review, we focus on the interplay of ideas pertaining to surfactants and block copolymers in three areas of self-assembly. First, we show how improved free energy models have evolved by applying ideas from surfactants to block copolymers and vice versa, giving rise to a unitary theoretical framework and better predictive capabilities for both classes of amphiphiles. Second we show that even though molecular packing arguments are often used to explain aggregate shape transitions resulting from self-assembly, the molecular packing considerations are more relevant in the case of surfactants whereas free energy criteria are relevant for block copolymers. Third, we show that even though the surfactant and block copolymer aggregates are small nanostructures, the size differences between them is significant enough to make the interfacial effects control the solubilization of molecules in surfactant micelles while the bulk interactions control the solubilization in block copolymer micelles. Finally, we conclude by identifying recent theoretical progress in adapting the micelle model to a wide variety of self-assembly phenomena and the challenges to modeling posed by emerging novel classes of amphiphiles with complex biological, inorganic or nanoparticle moieties. Published by Elsevier B.V.

Use of micro-positron emission tomography with (18)F-fallypride to measure the levels of dopamine receptor-D2 and (18)F-FDG as molecular imaging tracer in the pituitary glands and prolactinomas of Fischer-344 rats.

PubMed

Li, Ping; Gui, Songbai; Cao, Lei; Gao, Hua; Bai, Jiwei; Li, Chuzhong; Zhang, Yazhuo

2016-01-01

Dopamine receptor-D2 (DRD2) is the most important drug target in prolactinoma. The aim of this current study was to investigate the role of using micro-positron emission tomography (micro-PET) with (18)F-fallypride and (18)F-fluorodeoxyglucose ((18)F-FDG) as molecular imaging tracer in the pituitary glands and prolactinomas of Fischer-344 (F344) rats and detect the difference of the levels of DRD2 in the pituitary glands and prolactinomas of F344 rat prolactinoma models. Female F344 rat prolactinoma models were established by subcutaneous administration of 15 mg 17β-estradiol for 8 weeks. The growth of tumors was monitored by the small-animal magnetic resonance imaging and micro-PET. A series of molecular biological experiments were also performed 4 and 6 weeks after pump implantation. The micro-PET molecular imaging with (18)F-fallypride revealed a decreased expression of DRD2 in F344 rat prolactinoma models, but the micro-PET molecular imaging with (18)F-FDG presented an increased uptake in the prolactinoma compared with the pituitary gland. A decreasing trend of levels of DRD2 in F344 rat prolactinoma models was also detected by molecular biological experiments. From this, we can conclude that micro-PET with (18)F-fallypride and (18)F-FDG can be used to assess tumorigenesis of the prolactinomas in vivo and molecular imaging detection of DRD2 level in prolactinoma may be an indication of treatment effect in the animal experiment.

Multiple templates-based homology modeling enhances structure quality of AT1 receptor: validation by molecular dynamics and antagonist docking.

PubMed

Sokkar, Pandian; Mohandass, Shylajanaciyar; Ramachandran, Murugesan

2011-07-01

We present a comparative account on 3D-structures of human type-1 receptor (AT1) for angiotensin II (AngII), modeled using three different methodologies. AngII activates a wide spectrum of signaling responses via the AT1 receptor that mediates physiological control of blood pressure and diverse pathological actions in cardiovascular, renal, and other cell types. Availability of 3D-model of AT1 receptor would significantly enhance the development of new drugs for cardiovascular diseases. However, templates of AT1 receptor with low sequence similarity increase the complexity in straightforward homology modeling, and hence there is a need to evaluate different modeling methodologies in order to use the models for sensitive applications such as rational drug design. Three models were generated for AT1 receptor by, (1) homology modeling with bovine rhodopsin as template, (2) homology modeling with multiple templates and (3) threading using I-TASSER web server. Molecular dynamics (MD) simulation (15 ns) of models in explicit membrane-water system, Ramachandran plot analysis and molecular docking with antagonists led to the conclusion that multiple template-based homology modeling outweighs other methodologies for AT1 modeling.

Understanding molecular structure from molecular mechanics.

PubMed

Allinger, Norman L

2011-04-01

Molecular mechanics gives us a well known model of molecular structure. It is less widely recognized that valence bond theory gives us structures which offer a direct interpretation of molecular mechanics formulations and parameters. The electronic effects well-known in physical organic chemistry can be directly interpreted in terms of valence bond structures, and hence quantitatively calculated and understood. The basic theory is outlined in this paper, and examples of the effects, and their interpretation in illustrative examples is presented.

Mesoscale energy deposition footprint model for kiloelectronvolt cluster bombardment of solids.

PubMed

Russo, Michael F; Garrison, Barbara J

2006-10-15

Molecular dynamics simulations have been performed to model 5-keV C60 and Au3 projectile bombardment of an amorphous water substrate. The goal is to obtain detailed insights into the dynamics of motion in order to develop a straightforward and less computationally demanding model of the process of ejection. The molecular dynamics results provide the basis for the mesoscale energy deposition footprint model. This model provides a method for predicting relative yields based on information from less than 1 ps of simulation time.

An implicit divalent counterion force field for RNA molecular dynamics

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

Henke, Paul S.; Mak, Chi H., E-mail: cmak@usc.edu; Center of Applied Mathematical Sciences, University of Southern California, Los Angeles, California 90089

How to properly account for polyvalent counterions in a molecular dynamics simulation of polyelectrolytes such as nucleic acids remains an open question. Not only do counterions such as Mg{sup 2+} screen electrostatic interactions, they also produce attractive intrachain interactions that stabilize secondary and tertiary structures. Here, we show how a simple force field derived from a recently reported implicit counterion model can be integrated into a molecular dynamics simulation for RNAs to realistically reproduce key structural details of both single-stranded and base-paired RNA constructs. This divalent counterion model is computationally efficient. It works with existing atomistic force fields, or coarse-grainedmore » models may be tuned to work with it. We provide optimized parameters for a coarse-grained RNA model that takes advantage of this new counterion force field. Using the new model, we illustrate how the structural flexibility of RNA two-way junctions is modified under different salt conditions.« less

In silico method for modelling metabolism and gene product expression at genome scale

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

Lerman, Joshua A.; Hyduke, Daniel R.; Latif, Haythem

2012-07-03

Transcription and translation use raw materials and energy generated metabolically to create the macromolecular machinery responsible for all cellular functions, including metabolism. A biochemically accurate model of molecular biology and metabolism will facilitate comprehensive and quantitative computations of an organism's molecular constitution as a function of genetic and environmental parameters. Here we formulate a model of metabolism and macromolecular expression. Prototyping it using the simple microorganism Thermotoga maritima, we show our model accurately simulates variations in cellular composition and gene expression. Moreover, through in silico comparative transcriptomics, the model allows the discovery of new regulons and improving the genome andmore » transcription unit annotations. Our method presents a framework for investigating molecular biology and cellular physiology in silico and may allow quantitative interpretation of multi-omics data sets in the context of an integrated biochemical description of an organism.« less

Molecular modeling, simulation and virtual screening of MurD ligase protein from Salmonella typhimurium LT2.

PubMed

Samal, Himanshu Bhusan; Das, Jugal Kishore; Mahapatra, Rajani Kanta; Suar, Mrutyunjay

2015-01-01

The Mur enzymes of the peptidoglycan biosynthesis pathway constitute ideal targets for the design of new classes of antimicrobial inhibitors in Gram-negative bacteria. We built a homology model of MurD of Salmonella typhimurium LT2 using MODELLER (9v12) software. 'The homology model was subjected to energy minimization by molecular dynamics (MD) simulation study with GROMACS software for a simulation time of 20 ns in water environment. The model was subjected for virtual screening study from the Zinc Database using Dockblaster software. Inhibition assay for the best inhibitor, 3-(amino methyl)-n-(4-methoxyphenyl) aniline, by flow cytometric analysis revealed the effective inhibition of peptidoglycan biosynthesis. Results from this study provide new insights for the molecular understanding and development of new antibacterial drugs against the pathogen. Copyright © 2015 Elsevier Inc. All rights reserved.

Evaluation of protein-protein docking model structures using all-atom molecular dynamics simulations combined with the solution theory in the energy representation

NASA Astrophysics Data System (ADS)

Takemura, Kazuhiro; Guo, Hao; Sakuraba, Shun; Matubayasi, Nobuyuki; Kitao, Akio

2012-12-01

We propose a method to evaluate binding free energy differences among distinct protein-protein complex model structures through all-atom molecular dynamics simulations in explicit water using the solution theory in the energy representation. Complex model structures are generated from a pair of monomeric structures using the rigid-body docking program ZDOCK. After structure refinement by side chain optimization and all-atom molecular dynamics simulations in explicit water, complex models are evaluated based on the sum of their conformational and solvation free energies, the latter calculated from the energy distribution functions obtained from relatively short molecular dynamics simulations of the complex in water and of pure water based on the solution theory in the energy representation. We examined protein-protein complex model structures of two protein-protein complex systems, bovine trypsin/CMTI-1 squash inhibitor (PDB ID: 1PPE) and RNase SA/barstar (PDB ID: 1AY7), for which both complex and monomer structures were determined experimentally. For each system, we calculated the energies for the crystal complex structure and twelve generated model structures including the model most similar to the crystal structure and very different from it. In both systems, the sum of the conformational and solvation free energies tended to be lower for the structure similar to the crystal. We concluded that our energy calculation method is useful for selecting low energy complex models similar to the crystal structure from among a set of generated models.

Evaluation of protein-protein docking model structures using all-atom molecular dynamics simulations combined with the solution theory in the energy representation.

PubMed

Takemura, Kazuhiro; Guo, Hao; Sakuraba, Shun; Matubayasi, Nobuyuki; Kitao, Akio

2012-12-07

We propose a method to evaluate binding free energy differences among distinct protein-protein complex model structures through all-atom molecular dynamics simulations in explicit water using the solution theory in the energy representation. Complex model structures are generated from a pair of monomeric structures using the rigid-body docking program ZDOCK. After structure refinement by side chain optimization and all-atom molecular dynamics simulations in explicit water, complex models are evaluated based on the sum of their conformational and solvation free energies, the latter calculated from the energy distribution functions obtained from relatively short molecular dynamics simulations of the complex in water and of pure water based on the solution theory in the energy representation. We examined protein-protein complex model structures of two protein-protein complex systems, bovine trypsin/CMTI-1 squash inhibitor (PDB ID: 1PPE) and RNase SA/barstar (PDB ID: 1AY7), for which both complex and monomer structures were determined experimentally. For each system, we calculated the energies for the crystal complex structure and twelve generated model structures including the model most similar to the crystal structure and very different from it. In both systems, the sum of the conformational and solvation free energies tended to be lower for the structure similar to the crystal. We concluded that our energy calculation method is useful for selecting low energy complex models similar to the crystal structure from among a set of generated models.

From deep TLS validation to ensembles of atomic models built from elemental motions

DOE PAGES

Urzhumtsev, Alexandre; Afonine, Pavel V.; Van Benschoten, Andrew H.; ...

2015-07-28

The translation–libration–screw model first introduced by Cruickshank, Schomaker and Trueblood describes the concerted motions of atomic groups. Using TLS models can improve the agreement between calculated and experimental diffraction data. Because the T, L and S matrices describe a combination of atomic vibrations and librations, TLS models can also potentially shed light on molecular mechanisms involving correlated motions. However, this use of TLS models in mechanistic studies is hampered by the difficulties in translating the results of refinement into molecular movement or a structural ensemble. To convert the matrices into a constituent molecular movement, the matrix elements must satisfy severalmore » conditions. Refining the T, L and S matrix elements as independent parameters without taking these conditions into account may result in matrices that do not represent concerted molecular movements. Here, a mathematical framework and the computational tools to analyze TLS matrices, resulting in either explicit decomposition into descriptions of the underlying motions or a report of broken conditions, are described. The description of valid underlying motions can then be output as a structural ensemble. All methods are implemented as part of the PHENIX project.« less

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

McLaughlin, E.; Gupta, S.

This project mainly involves a molecular dynamics and Monte Carlo study of the effect of molecular shape on thermophysical properties of bulk fluids with an emphasis on the aromatic hydrocarbon liquids. In this regard we have studied the modeling, simulation methodologies, and predictive and correlating methods for thermodynamic properties of fluids of nonspherical molecules. In connection with modeling we have studied the use of anisotropic site-site potentials, through a modification of the Gay-Berne Gaussian overlap potential, to successfully model the aromatic rings after adding the necessary electrostatic moments. We have also shown these interaction sites should be located at themore » geometric centers of the chemical groups. In connection with predictive methods, we have shown two perturbation type theories to work well for fluids modeled using one-center anisotropic potentials and the possibility exists for extending these to anisotropic site-site models. In connection with correlation methods, we have studied, through simulations, the effect of molecular shape on the attraction term in the generalized van der Waals equation of state for fluids of nonspherical molecules and proposed a possible form which is to be studied further. We have successfully studied the vector and parallel processing aspects of molecular simulations for fluids of nonspherical molecules.« less

The activation strain model and molecular orbital theory

PubMed Central

Wolters, Lando P; Bickelhaupt, F Matthias

2015-01-01

The activation strain model is a powerful tool for understanding reactivity, or inertness, of molecular species. This is done by relating the relative energy of a molecular complex along the reaction energy profile to the structural rigidity of the reactants and the strength of their mutual interactions: ΔE(ζ) = ΔEstrain(ζ) + ΔEint(ζ). We provide a detailed discussion of the model, and elaborate on its strong connection with molecular orbital theory. Using these approaches, a causal relationship is revealed between the properties of the reactants and their reactivity, e.g., reaction barriers and plausible reaction mechanisms. This methodology may reveal intriguing parallels between completely different types of chemical transformations. Thus, the activation strain model constitutes a unifying framework that furthers the development of cross-disciplinary concepts throughout various fields of chemistry. We illustrate the activation strain model in action with selected examples from literature. These examples demonstrate how the methodology is applied to different research questions, how results are interpreted, and how insights into one chemical phenomenon can lead to an improved understanding of another, seemingly completely different chemical process. WIREs Comput Mol Sci 2015, 5:324–343. doi: 10.1002/wcms.1221 PMID:26753009

Insights into host-pathogen interactions from state-of-the-art animal models of respiratory Pseudomonas aeruginosa infections.

PubMed

Lorenz, Anne; Pawar, Vinay; Häussler, Susanne; Weiss, Siegfried

2016-11-01

Pseudomonas aeruginosa is an important opportunistic pathogen that can cause acute respiratory infections in immunocompetent patients or chronic infections in immunocompromised individuals and in patients with cystic fibrosis. When acquiring the chronic infection state, bacteria are encapsulated within biofilm structures enabling them to withstand diverse environmental assaults, including immune reactions and antimicrobial therapy. Understanding the molecular interactions within the bacteria, as well as with the host or other bacteria, is essential for developing innovative treatment strategies. Such knowledge might be accumulated in vitro. However, it is ultimately necessary to confirm these findings in vivo. In the present Review, we describe state-of-the-art in vivo models that allow studying P. aeruginosa infections in molecular detail. The portrayed mammalian models exclusively focus on respiratory infections. The data obtained by alternative animal models which lack lung tissue, often provide molecular insights that are easily transferable to mammals. Importantly, these surrogate in vivo systems reveal complex molecular interactions of P. aeruginosa with the host. Herein, we also provide a critical assessment of the advantages and disadvantages of such models. © 2016 Federation of European Biochemical Societies.

Learning Kinetic Monte Carlo Models of Condensed Phase High Temperature Chemistry from Molecular Dynamics

NASA Astrophysics Data System (ADS)

Yang, Qian; Sing-Long, Carlos; Chen, Enze; Reed, Evan

2017-06-01

Complex chemical processes, such as the decomposition of energetic materials and the chemistry of planetary interiors, are typically studied using large-scale molecular dynamics simulations that run for weeks on high performance parallel machines. These computations may involve thousands of atoms forming hundreds of molecular species and undergoing thousands of reactions. It is natural to wonder whether this wealth of data can be utilized to build more efficient, interpretable, and predictive models. In this talk, we will use techniques from statistical learning to develop a framework for constructing Kinetic Monte Carlo (KMC) models from molecular dynamics data. We will show that our KMC models can not only extrapolate the behavior of the chemical system by as much as an order of magnitude in time, but can also be used to study the dynamics of entirely different chemical trajectories with a high degree of fidelity. Then, we will discuss three different methods for reducing our learned KMC models, including a new and efficient data-driven algorithm using L1-regularization. We demonstrate our framework throughout on a system of high-temperature high-pressure liquid methane, thought to be a major component of gas giant planetary interiors.

Structure–property reduced order model for viscosity prediction in single-component CO 2 -binding organic liquids

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

Cantu, David C.; Malhotra, Deepika; Koech, Phillip K.

2016-01-01

CO2 capture from power generation with aqueous solvents remains energy intensive due to the high water content of the current technology, or the high viscosity of non-aqueous alternatives. Quantitative reduced models, connecting molecular structure to bulk properties, are key for developing structure-property relationships that enable molecular design. In this work, we describe such a model that quantitatively predicts viscosities of CO2 binding organic liquids (CO2BOLs) based solely on molecular structure and the amount of bound CO2. The functional form of the model correlates the viscosity with the CO2 loading and an electrostatic term describing the charge distribution between the CO2-bearingmore » functional group and the proton-receiving amine. Molecular simulations identify the proton shuttle between these groups within the same molecule to be the critical indicator of low viscosity. The model, developed to allow for quick screening of solvent libraries, paves the way towards the rational design of low viscosity non-aqueous solvent systems for post-combustion CO2 capture. Following these theoretical recommendations, synthetic efforts of promising candidates and viscosity measurement provide experimental validation and verification.« less

Improved Prediction of Blood-Brain Barrier Permeability Through Machine Learning with Combined Use of Molecular Property-Based Descriptors and Fingerprints.

PubMed

Yuan, Yaxia; Zheng, Fang; Zhan, Chang-Guo

2018-03-21

Blood-brain barrier (BBB) permeability of a compound determines whether the compound can effectively enter the brain. It is an essential property which must be accounted for in drug discovery with a target in the brain. Several computational methods have been used to predict the BBB permeability. In particular, support vector machine (SVM), which is a kernel-based machine learning method, has been used popularly in this field. For SVM training and prediction, the compounds are characterized by molecular descriptors. Some SVM models were based on the use of molecular property-based descriptors (including 1D, 2D, and 3D descriptors) or fragment-based descriptors (known as the fingerprints of a molecule). The selection of descriptors is critical for the performance of a SVM model. In this study, we aimed to develop a generally applicable new SVM model by combining all of the features of the molecular property-based descriptors and fingerprints to improve the accuracy for the BBB permeability prediction. The results indicate that our SVM model has improved accuracy compared to the currently available models of the BBB permeability prediction.

Synthesis of model humic substances: a mechanistic study using controllable H/D exchange and Fourier transform ion cyclotron resonance mass spectrometry.

PubMed

Zherebker, Alexander Ya; Airapetyan, David; Konstantinov, Andrey I; Kostyukevich, Yury I; Kononikhin, Alexey S; Popov, Igor A; Zaitsev, Kirill V; Nikolaev, Eugene N; Perminova, Irina V

2015-07-07

The products of the oxidative coupling of phenols are frequently used as synthetic analogues to natural humic substances (HS) for biomedical research. However, their molecular compositions and exact structures remain largely unknown. The objective of this study was to develop a novel approach for the molecular-level analysis of phenolic polymerisates that is capable of inventorying molecular constituents and resolving their distinct structural formulas. For this purpose, we have synthesized the model HS using the oxidative coupling of a specifically designed phenylpropanoic monomer, 3-(4-hydroxy-3-methoxyphenyl)-3-oxopropionic acid, to hydroquinone. We have characterized the synthesized model HS using high resolution Fourier transform ion cyclotron resonance mass spectrometry (FTICR MS), (1)H NMR spectroscopy, and controllable hydrogen/deuterium (H/D) exchange. We succeeded in the molecular inventory of the model HS. The assigned molecular formulas occupied the substantial space of CHO compositions in the Van Krevelen diagram with a maximum density found in the regions of tannins and lignins, resembling those of natural HS. To identify the exact structural formulas of the individual constituents in the model HS, we have applied selective H/D exchange of non-labile backbone protons by a choice of basic or acidic catalytic conditions followed by FTICR MS. The determined formulas allowed us to verify the proposed pathways of hydroxylation and carboxylation in the course of the phenolic coupling and to identify the acetylation of aromatic rings as an important side reaction. We conclude that the proposed analytical approach may be used to identify the molecular carriers of biological activity within the phenolic polymerisates and eventually within natural HS.

A software platform for continuum modeling of ion channels based on unstructured mesh

NASA Astrophysics Data System (ADS)

Tu, B.; Bai, S. Y.; Chen, M. X.; Xie, Y.; Zhang, L. B.; Lu, B. Z.

2014-01-01

Most traditional continuum molecular modeling adopted finite difference or finite volume methods which were based on a structured mesh (grid). Unstructured meshes were only occasionally used, but an increased number of applications emerge in molecular simulations. To facilitate the continuum modeling of biomolecular systems based on unstructured meshes, we are developing a software platform with tools which are particularly beneficial to those approaches. This work describes the software system specifically for the simulation of a typical, complex molecular procedure: ion transport through a three-dimensional channel system that consists of a protein and a membrane. The platform contains three parts: a meshing tool chain for ion channel systems, a parallel finite element solver for the Poisson-Nernst-Planck equations describing the electrodiffusion process of ion transport, and a visualization program for continuum molecular modeling. The meshing tool chain in the platform, which consists of a set of mesh generation tools, is able to generate high-quality surface and volume meshes for ion channel systems. The parallel finite element solver in our platform is based on the parallel adaptive finite element package PHG which wass developed by one of the authors [1]. As a featured component of the platform, a new visualization program, VCMM, has specifically been developed for continuum molecular modeling with an emphasis on providing useful facilities for unstructured mesh-based methods and for their output analysis and visualization. VCMM provides a graphic user interface and consists of three modules: a molecular module, a meshing module and a numerical module. A demonstration of the platform is provided with a study of two real proteins, the connexin 26 and hemolysin ion channels.

Radiomics biomarkers for accurate tumor progression prediction of oropharyngeal cancer

NASA Astrophysics Data System (ADS)

Hadjiiski, Lubomir; Chan, Heang-Ping; Cha, Kenny H.; Srinivasan, Ashok; Wei, Jun; Zhou, Chuan; Prince, Mark; Papagerakis, Silvana

2017-03-01

Accurate tumor progression prediction for oropharyngeal cancers is crucial for identifying patients who would best be treated with optimized treatment and therefore minimize the risk of under- or over-treatment. An objective decision support system that can merge the available radiomics, histopathologic and molecular biomarkers in a predictive model based on statistical outcomes of previous cases and machine learning may assist clinicians in making more accurate assessment of oropharyngeal tumor progression. In this study, we evaluated the feasibility of developing individual and combined predictive models based on quantitative image analysis from radiomics, histopathology and molecular biomarkers for oropharyngeal tumor progression prediction. With IRB approval, 31, 84, and 127 patients with head and neck CT (CT-HN), tumor tissue microarrays (TMAs) and molecular biomarker expressions, respectively, were collected. For 8 of the patients all 3 types of biomarkers were available and they were sequestered in a test set. The CT-HN lesions were automatically segmented using our level sets based method. Morphological, texture and molecular based features were extracted from CT-HN and TMA images, and selected features were merged by a neural network. The classification accuracy was quantified using the area under the ROC curve (AUC). Test AUCs of 0.87, 0.74, and 0.71 were obtained with the individual predictive models based on radiomics, histopathologic, and molecular features, respectively. Combining the radiomics and molecular models increased the test AUC to 0.90. Combining all 3 models increased the test AUC further to 0.94. This preliminary study demonstrates that the individual domains of biomarkers are useful and the integrated multi-domain approach is most promising for tumor progression prediction.

Molecular design of new aggrecanases-2 inhibitors.

PubMed

Shan, Zhi Jie; Zhai, Hong Lin; Huang, Xiao Yan; Li, Li Na; Zhang, Xiao Yun

2013-10-01

Aggrecanases-2 is a very important potential drug target for the treatment of osteoarthritis. In this study, a series of known aggrecanases-2 inhibitors was analyzed by the technologies of three-dimensional quantitative structure-activity relationships (3D-QSAR) and molecular docking. Two 3D-QSAR models, which based on comparative molecular field analysis (CoMFA) and comparative molecular similarity analysis (CoMSIA) methods, were established. Molecular docking was employed to explore the details of the interaction between inhibitors and aggrecanases-2 protein. According to the analyses for these models, several new potential inhibitors with higher activity predicted were designed, and were supported by the simulation of molecular docking. This work propose the fast and effective approach to design and prediction for new potential inhibitors, and the study of the interaction mechanism provide a better understanding for the inhibitors binding into the target protein, which will be useful for the structure-based drug design and modifications. Copyright © 2013 Elsevier Ltd. All rights reserved.

Study design requirements for RNA sequencing-based breast cancer diagnostics.

PubMed

Mer, Arvind Singh; Klevebring, Daniel; Grönberg, Henrik; Rantalainen, Mattias

2016-02-01

Sequencing-based molecular characterization of tumors provides information required for individualized cancer treatment. There are well-defined molecular subtypes of breast cancer that provide improved prognostication compared to routine biomarkers. However, molecular subtyping is not yet implemented in routine breast cancer care. Clinical translation is dependent on subtype prediction models providing high sensitivity and specificity. In this study we evaluate sample size and RNA-sequencing read requirements for breast cancer subtyping to facilitate rational design of translational studies. We applied subsampling to ascertain the effect of training sample size and the number of RNA sequencing reads on classification accuracy of molecular subtype and routine biomarker prediction models (unsupervised and supervised). Subtype classification accuracy improved with increasing sample size up to N = 750 (accuracy = 0.93), although with a modest improvement beyond N = 350 (accuracy = 0.92). Prediction of routine biomarkers achieved accuracy of 0.94 (ER) and 0.92 (Her2) at N = 200. Subtype classification improved with RNA-sequencing library size up to 5 million reads. Development of molecular subtyping models for cancer diagnostics requires well-designed studies. Sample size and the number of RNA sequencing reads directly influence accuracy of molecular subtyping. Results in this study provide key information for rational design of translational studies aiming to bring sequencing-based diagnostics to the clinic.

Physicochemical properties of the modeled structure of astacin metalloprotease moulting enzyme NAS-36 and mapping the druggable allosteric space of Heamonchus contortus, Brugia malayi and Ceanorhabditis elegans via molecular dynamics simulation.

PubMed

Sharma, Om Prakash; Agrawal, Sonali; Kumar, M Suresh

2013-12-01

Nematodes represent the second largest phylum in the animal kingdom. It is the most abundant species (500,000) in the planet. It causes chronic, debilitating infections worldwide such as ascariasis, trichuriasis, hookworm, enterobiasis, strongyloidiasis, filariasis and trichinosis, among others. Molecular modeling tools can play an important role in the identification and structural investigation of molecular targets that can act as a vital candidate against filariasis. In this study, sequence analysis of NAS-36 from H. contortus (Heamonchus contortus), B. malayi (Brugia malayi) and C. elegans (Ceanorhabditis elegans) has been performed, in order to identify the conserved residues. Tertiary structure was developed for an insight into the molecular structure of the enzyme. Molecular Dynamics Simulation (MDS) studies have been carried out to analyze the stability and the physical properties of the proposed enzyme models in the H. contortus, B. malayi and C. elegans. Moreover, the drug binding sites have been mapped for inhibiting the function of NAS-36 enzyme. The molecular identity of this protease could eventually demonstrate how ex-sheathment is regulated, as well as provide a potential target of anthelmintics for the prevention of nematode infections.

Experimental and molecular docking studies on DNA binding interaction of adefovir dipivoxil: Advances toward treatment of hepatitis B virus infections

NASA Astrophysics Data System (ADS)

Shahabadi, Nahid; Falsafi, Monireh

The toxic interaction of adefovir dipivoxil with calf thymus DNA (CT-DNA) was investigated in vitro under simulated physiological conditions by multi-spectroscopic techniques and molecular modeling study. The fluorescence spectroscopy and UV absorption spectroscopy indicated drug interacted with CT-DNA in a groove binding mode. The binding constant of UV-visible and the number of binding sites were 3.33 ± 0.2 × 104 L mol-1and 0.99, respectively. The fluorimetric studies showed that the reaction between the drug and CT-DNA is exothermic (ΔH = 34.4 kJ mol-1; ΔS = 184.32 J mol-1 K-1). Circular dichroism spectroscopy (CD) was employed to measure the conformational change of CT-DNA in the presence of adefovir dipivoxil, which verified the groove binding mode. Furthermore, the drug induces detectable changes in its viscosity. The molecular modeling results illustrated that adefovir strongly binds to groove of DNA by relative binding energy of docked structure -16.83 kJ mol-1. This combination of multiple spectroscopic techniques and molecular modeling methods can be widely used in the investigation on the toxic interaction of small molecular pollutants and drugs with bio macromolecules, which contributes to clarify the molecular mechanism of toxicity or side effect in vivo.

Potential human cholesterol esterase inhibitor design: benefits from the molecular dynamics simulations and pharmacophore modeling studies.

PubMed

John, Shalini; Thangapandian, Sundarapandian; Lee, Keun Woo

2012-01-01

Human pancreatic cholesterol esterase (hCEase) is one of the lipases found to involve in the digestion of large and broad spectrum of substrates including triglycerides, phospholipids, cholesteryl esters, etc. The presence of bile salts is found to be very important for the activation of hCEase. Molecular dynamic simulations were performed for the apoform and bile salt complexed form of hCEase using the co-ordinates of two bile salts from bovine CEase. The stability of the systems throughout the simulation time was checked and two representative structures from the highly populated regions were selected using cluster analysis. These two representative structures were used in pharmacophore model generation. The generated pharmacophore models were validated and used in database screening. The screened hits were refined for their drug-like properties based on Lipinski's rule of five and ADMET properties. The drug-like compounds were further refined by molecular docking simulation using GOLD program based on the GOLD fitness score, mode of binding, and molecular interactions with the active site amino acids. Finally, three hits of novel scaffolds were selected as potential leads to be used in novel and potent hCEase inhibitor design. The stability of binding modes and molecular interactions of these final hits were re-assured by molecular dynamics simulations.

Deep Potential Molecular Dynamics: A Scalable Model with the Accuracy of Quantum Mechanics

NASA Astrophysics Data System (ADS)

Zhang, Linfeng; Han, Jiequn; Wang, Han; Car, Roberto; E, Weinan

2018-04-01

We introduce a scheme for molecular simulations, the deep potential molecular dynamics (DPMD) method, based on a many-body potential and interatomic forces generated by a carefully crafted deep neural network trained with ab initio data. The neural network model preserves all the natural symmetries in the problem. It is first-principles based in the sense that there are no ad hoc components aside from the network model. We show that the proposed scheme provides an efficient and accurate protocol in a variety of systems, including bulk materials and molecules. In all these cases, DPMD gives results that are essentially indistinguishable from the original data, at a cost that scales linearly with system size.

Challenges and Development of a Multi-Scale Computational Model for Photosystem I Decoupled Energy Conversion

DTIC Science & Technology

2013-06-01

Applications of Molecular Modeling to Challenges in Clean Energy; Fitzgerald, G., et al .; ACS Symposium Series; American Chemical Society: Washington, DC...to 178 In Applications of Molecular Modeling to Challenges in Clean Energy; Fitzgerald, G., et al .; ACS Symposium Series; American Chemical Society...Washington, DC, 2013. developmodels of spectral properties and energy transfer kinetics (20–22). Ivashin et al . optimized select ligands (α

Mixing coarse-grained and fine-grained water in molecular dynamics simulations of a single system.

PubMed

Riniker, Sereina; van Gunsteren, Wilfred F

2012-07-28

The use of a supra-molecular coarse-grained (CG) model for liquid water as solvent in molecular dynamics simulations of biomolecules represented at the fine-grained (FG) atomic level of modelling may reduce the computational effort by one or two orders of magnitude. However, even if the pure FG model and the pure CG model represent the properties of the particular substance of interest rather well, their application in a hybrid FG/CG system containing varying ratios of FG versus CG particles is highly non-trivial, because it requires an appropriate balance between FG-FG, FG-CG, and CG-CG energies, and FG and CG entropies. Here, the properties of liquid water are used to calibrate the FG-CG interactions for the simple-point-charge water model at the FG level and a recently proposed supra-molecular water model at the CG level that represents five water molecules by one CG bead containing two interaction sites. Only two parameters are needed to reproduce different thermodynamic and dielectric properties of liquid water at physiological temperature and pressure for various mole fractions of CG water in FG water. The parametrisation strategy for the FG-CG interactions is simple and can be easily transferred to interactions between atomistic biomolecules and CG water.

Molecular modelling of protein-protein/protein-solvent interactions

NASA Astrophysics Data System (ADS)

Luchko, Tyler

The inner workings of individual cells are based on intricate networks of protein-protein interactions. However, each of these individual protein interactions requires a complex physical interaction between proteins and their aqueous environment at the atomic scale. In this thesis, molecular dynamics simulations are used in three theoretical studies to gain insight at the atomic scale about protein hydration, protein structure and tubulin-tubulin (protein-protein) interactions, as found in microtubules. Also presented, in a fourth project, is a molecular model of solvation coupled with the Amber molecular modelling package, to facilitate further studies without the need of explicitly modelled water. Basic properties of a minimally solvated protein were calculated through an extended study of myoglobin hydration with explicit solvent, directly investigating water and protein polarization. Results indicate a close correlation between polarization of both water and protein and the onset of protein function. The methodology of explicit solvent molecular dynamics was further used to study tubulin and microtubules. Extensive conformational sampling of the carboxy-terminal tails of 8-tubulin was performed via replica exchange molecular dynamics, allowing the characterisation of the flexibility, secondary structure and binding domains of the C-terminal tails through statistical analysis methods. Mechanical properties of tubulin and microtubules were calculated with adaptive biasing force molecular dynamics. The function of the M-loop in microtubule stability was demonstrated in these simulations. The flexibility of this loop allowed constant contacts between the protofilaments to be maintained during simulations while the smooth deformation provided a spring-like restoring force. Additionally, calculating the free energy profile between the straight and bent tubulin configurations was used to test the proposed conformational change in tubulin, thought to cause microtubule destabilization. No conformational change was observed but a nucleotide dependent 'softening' of the interaction was found instead, suggesting that an entropic force in a microtubule configuration could be the mechanism of microtubule collapse. Finally, to overcome much of the computational costs associated with explicit soIvent calculations, a new combination of molecular dynamics with the 3D-reference interaction site model (3D-RISM) of solvation was integrated into the Amber molecular dynamics package. Our implementation of 3D-RISM shows excellent agreement with explicit solvent free energy calculations. Several optimisation techniques, including a new multiple time step method, provide a nearly 100 fold performance increase, giving similar computational performance to explicit solvent.

Computer Code for Interpreting 13C NMR Relaxation Measurements with Specific Models of Molecular Motion: The Rigid Isotropic and Symmetric Top Rotor Models and the Flexible Symmetric Top Rotor Model

DTIC Science & Technology

2017-01-01

unlimited. 13. SUPPLEMENTARY NOTES 14. ABSTRACT: Carbon-13 nuclear magnetic resonance (13C NMR) spectroscopy is a powerful technique for...FLEXIBLE SYMMETRIC TOP ROTOR MODEL 1. INTRODUCTION Nuclear magnetic resonance (NMR) spectroscopy is a tremendously powerful technique for...application of NMR spectroscopy concerns the property of molecular motion, which is related to many physical, and even biological, functions of molecules in

Quantum mechanical force field for water with explicit electronic polarization.

PubMed

Han, Jaebeom; Mazack, Michael J M; Zhang, Peng; Truhlar, Donald G; Gao, Jiali

2013-08-07

A quantum mechanical force field (QMFF) for water is described. Unlike traditional approaches that use quantum mechanical results and experimental data to parameterize empirical potential energy functions, the present QMFF uses a quantum mechanical framework to represent intramolecular and intermolecular interactions in an entire condensed-phase system. In particular, the internal energy terms used in molecular mechanics are replaced by a quantum mechanical formalism that naturally includes electronic polarization due to intermolecular interactions and its effects on the force constants of the intramolecular force field. As a quantum mechanical force field, both intermolecular interactions and the Hamiltonian describing the individual molecular fragments can be parameterized to strive for accuracy and computational efficiency. In this work, we introduce a polarizable molecular orbital model Hamiltonian for water and for oxygen- and hydrogen-containing compounds, whereas the electrostatic potential responsible for intermolecular interactions in the liquid and in solution is modeled by a three-point charge representation that realistically reproduces the total molecular dipole moment and the local hybridization contributions. The present QMFF for water, which is called the XP3P (explicit polarization with three-point-charge potential) model, is suitable for modeling both gas-phase clusters and liquid water. The paper demonstrates the performance of the XP3P model for water and proton clusters and the properties of the pure liquid from about 900 × 10(6) self-consistent-field calculations on a periodic system consisting of 267 water molecules. The unusual dipole derivative behavior of water, which is incorrectly modeled in molecular mechanics, is naturally reproduced as a result of an electronic structural treatment of chemical bonding by XP3P. We anticipate that the XP3P model will be useful for studying proton transport in solution and solid phases as well as across biological ion channels through membranes.

Validation of Potential Models for Li2O in Classical Molecular Dynamics Simulation

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

Oda, Takuji; Oya, Yasuhisa; Tanaka, Satoru

2007-08-01

Four Buckingham-type pairwise potential models for Li2O were assessed by molecular static and dynamics simulations. In the static simulation, all models afforded acceptable agreement with experimental values and ab initio calculation results for the crystalline properties. Moreover, the superionic phase transition was realized in the dynamics simulation. However, the Li diffusivity and the lattice expansion were not adequately reproduced at the same time by any model. When using these models in future radiation simulation, these features should be taken into account, in order to reduce the model dependency of the results.

Effects of molecular and particle scatterings on the model parameter for remote-sensing reflectance.

PubMed

Lee, ZhongPing; Carder, Kendall L; Du, KePing

2004-09-01

For optically deep waters, remote-sensing reflectance (r(rs)) is traditionally expressed as the ratio of the backscattering coefficient (b(b)) to the sum of absorption and backscattering coefficients (a + b(b)) that multiples a model parameter (g, or the so-called f'/Q). Parameter g is further expressed as a function of b(b)/(a + b(b)) (or b(b)/a) to account for its variation that is due to multiple scattering. With such an approach, the same g value will be derived for different a and b(b) values that provide the same ratio. Because g is partially a measure of the angular distribution of upwelling light, and the angular distribution from molecular scattering is quite different from that of particle scattering; g values are expected to vary with different scattering distributions even if the b(b)/a ratios are the same. In this study, after numerically demonstrating the effects of molecular and particle scatterings on the values of g, an innovative r(rs) model is developed. This new model expresses r(rs) in two separate terms: one governed by the phase function of molecular scattering and one governed by the phase function of particle scattering, with a model parameter introduced for each term. In this way the phase function effects from molecular and particle scatterings are explicitly separated and accounted for. This new model provides an analytical tool to understand and quantify the phase-function effects on r(rs), and a platform to calculate r(rs) spectrum quickly and accurately that is required for remote-sensing applications.

Peclet number as affected by molecular diffusion controls transient anomalous transport in alluvial aquifer-aquitard complexes

USGS Publications Warehouse

Zhang, Yong; Green, Christopher T.; Tick, Geoffrey R.

2015-01-01

This study evaluates the role of the Peclet number as affected by molecular diffusion in transient anomalous transport, which is one of the major knowledge gaps in anomalous transport, by combining Monte Carlo simulations and stochastic model analysis. Two alluvial settings containing either short- or long-connected hydrofacies are generated and used as media for flow and transport modeling. Numerical experiments show that 1) the Peclet number affects both the duration of the power-law segment of tracer breakthrough curves (BTCs) and the transition rate from anomalous to Fickian transport by determining the solute residence time for a given low-permeability layer, 2) mechanical dispersion has a limited contribution to the anomalous characteristics of late-time transport as compared to molecular diffusion due to an almost negligible velocity in floodplain deposits, and 3) the initial source dimensions only enhance the power-law tail of the BTCs at short travel distances. A tempered stable stochastic (TSS) model is then applied to analyze the modeled transport. Applications show that the time-nonlocal parameters in the TSS model relate to the Peclet number, Pe. In particular, the truncation parameter in the TSS model increases nonlinearly with a decrease in Pe due to the decrease of the mean residence time, and the capacity coefficient increases with an increase in molecular diffusion which is probably due to the increase in the number of immobile particles. The above numerical experiments and stochastic analysis therefore reveal that the Peclet number as affected by molecular diffusion controls transient anomalous transport in alluvial aquifer–aquitard complexes.

Design of Novel Chemotherapeutic Agents Targeting Checkpoint Kinase 1 Using 3D-QSAR Modeling and Molecular Docking Methods.

PubMed

Balupuri, Anand; Balasubramanian, Pavithra K; Cho, Seung J

2016-01-01

Checkpoint kinase 1 (Chk1) has emerged as a potential therapeutic target for design and development of novel anticancer drugs. Herein, we have performed three-dimensional quantitative structure-activity relationship (3D-QSAR) and molecular docking analyses on a series of diazacarbazoles to design potent Chk1 inhibitors. 3D-QSAR models were developed using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) techniques. Docking studies were performed using AutoDock. The best CoMFA and CoMSIA models exhibited cross-validated correlation coefficient (q2) values of 0.631 and 0.585, and non-cross-validated correlation coefficient (r2) values of 0.933 and 0.900, respectively. CoMFA and CoMSIA models showed reasonable external predictabilities (r2 pred) of 0.672 and 0.513, respectively. A satisfactory performance in the various internal and external validation techniques indicated the reliability and robustness of the best model. Docking studies were performed to explore the binding mode of inhibitors inside the active site of Chk1. Molecular docking revealed that hydrogen bond interactions with Lys38, Glu85 and Cys87 are essential for Chk1 inhibitory activity. The binding interaction patterns observed during docking studies were complementary to 3D-QSAR results. Information obtained from the contour map analysis was utilized to design novel potent Chk1 inhibitors. Their activities and binding affinities were predicted using the derived model and docking studies. Designed inhibitors were proposed as potential candidates for experimental synthesis.

A MURINE MODEL FOR LOW MOLECULAR WEIGHT CHEMICALS: DIFFERENTIATION OF RESPIRATORY SENSITIZERS (TMA) FROM CONTACT SENSITIZERS (DNFB)

EPA Science Inventory

Exposure to low molecular weight (LMW) chemicals contributes to both dermal and respiratory sensitization and is an important occupational health problem. Our goal was to establish an in vivo murine model for hazard identification of LMW chemicals that have the potential to indu...

Investigation of antigen-antibody interactions of sulfonamides with a monoclonal antibody in a fluorescence polarization immunoassay using 3D-QSAR models

USDA-ARS?s Scientific Manuscript database

A three-dimensional quantitative structure-activity relationship (3D-QSAR) model of sulfonamide analogs binding a monoclonal antibody (MAbSMR) produced against sulfamerazine was carried out by Distance Comparison (DISCOtech), comparative molecular field analysis (CoMFA), and comparative molecular si...

Broad-specificity immunoassay for O,O-diethyl organophosphorus pesticides: Application of molecular modeling to improve assay sensitivity and study antibody recognition

USDA-ARS?s Scientific Manuscript database

A monoclonal antibody (MAb) against 4-(diethoxyphosphorothioyloxy)benzoic acid (hapten 1) was raised and used to develop a broad-specificity competitive indirect enzyme-linked immunosorbent assay (ciELISA) for 14 O,O-diethyl organophosphorus pesticides (OPs). Computer-assisted molecular modeling was...

Fischer and Schrock Carbene Complexes: A Molecular Modeling Exercise

ERIC Educational Resources Information Center

Montgomery, Craig D.

2015-01-01

An exercise in molecular modeling that demonstrates the distinctive features of Fischer and Schrock carbene complexes is presented. Semi-empirical calculations (PM3) demonstrate the singlet ground electronic state, restricted rotation about the C-Y bond, the positive charge on the carbon atom, and hence, the electrophilic nature of the Fischer…

Using the [beta][subscript 2]-Adrenoceptor for Structure-Based Drug Design

ERIC Educational Resources Information Center

Manallack, David T.; Chalmers, David K.; Yuriev, Elizabeth

2010-01-01

The topics of molecular modeling and drug design are studied in a medicinal chemistry course. The recently reported structures of several G protein-coupled receptors (GPCR) with bound ligands have been used to develop a simple computer-based experiment employing molecular-modeling software. Knowledge of the specific interactions between a ligand…

Meet the Molecules in Chocolate: Informal Opportunities for Building Thematic Molecular Models with Children

ERIC Educational Resources Information Center

Amey, Jennifer R.; Fletcher, Matthew D.; Fletcher, Rachael V.; Jones, Alison; Roberts, Erica W.; Roberts, Ieuan O.

2008-01-01

We describe the development and use of a molecular model building activity with a chocolate theme, suitable for a public presentation of chemistry through interaction with visitors to science festivals and museums, and as a special classroom activity during science weeks, and so forth. (Contains 3 figures.)

Looking beyond Lewis Structures: A General Chemistry Molecular Modeling Experiment Focusing on Physical Properties and Geometry

ERIC Educational Resources Information Center

Linenberger, Kimberly J.; Cole, Renee S.; Sarkar, Somnath

2011-01-01

We present a guided-inquiry experiment using Spartan Student Version, ready to be adapted and implemented into a general chemistry laboratory course. The experiment provides students an experience with Spartan Molecular Modeling software while discovering the relationships between the structure and properties of molecules. Topics discussed within…

Coupling Molecular Modeling to the Traditional "IR-ID" Exercise in the Introductory Organic Chemistry Laboratory

ERIC Educational Resources Information Center

Stokes-Huby, Heather; Vitale, Dale E.

2007-01-01

This exercise integrates the infrared unknown identification ("IR-ID") experiment common to most organic laboratory syllabi with computer molecular modeling. In this modification students are still required to identify unknown compounds from their IR spectra, but must additionally match some of the absorptions with computed frequencies they…

A New Three-Dimensional Educational Model Kit for Building DNA and RNA Molecules: Development and Evaluation

ERIC Educational Resources Information Center

Beltramini, Leila Maria; Araujo, Ana Paula Ulian; de Oliveira, Tales Henrique Goncalves; dos Santos Abel, Luciano Douglas; da Silva, Aparecido Rodrigues; dos Santos, Neusa Fernandes

2006-01-01

International specialized literature focused on research in biology education is sadly scarce, especially regarding biochemical and molecular aspects. In this light, researchers from this Centre for Structural Molecular Biotechnology developed and evaluated a three-dimensional educational model named "Building Life Molecules DNA and RNA." The…

New insights into heat induced structural changes of pectin methylesterase on fluorescence spectroscopy and molecular modeling basis

NASA Astrophysics Data System (ADS)

Nistor, Oana Viorela; Stănciuc, Nicoleta; Aprodu, Iuliana; Botez, Elisabeta

2014-07-01

Heat-induced structural changes of Aspergillus oryzae pectin methylesterase (PME) were studied by means of fluorescence spectroscopy and molecular modeling, whereas the functional enzyme stability was monitored by inactivation studies. The fluorescence spectroscopy experiments were performed at two pH value (4.5 and 7.0). At both pH values, the phase diagrams were linear, indicating the presence of two molecular species induced by thermal treatment. A red shift of 7 nm was observed at neutral pH by increasing temperature up to 60 °C, followed by a blue shift of 4 nm at 70 °C, suggesting significant conformational rearrangements. The quenching experiments using acrylamide and iodide demonstrate a more flexible conformation of enzyme with increasing temperature, especially at neutral pH. The experimental results were complemented with atomic level observations on PME model behavior after performing molecular dynamics simulations at different temperatures. The inactivation kinetics of PME in buffer solutions was fitted using a first-order kinetics model, resulting in activation energy of 241.4 ± 7.51 kJ mol-1.

Molecular modeling of polymer composite interactions with analytes in electronic nose sensors for environmental monitoring in International Space Station

NASA Technical Reports Server (NTRS)

Shevade, A. V.; Ryan, M. A.; Homer, M. L.; Manfreda, A. M.; Zhou, H.; Manatt, K.

2002-01-01

We report a molecular modeling study to investigate the polymer-carbon black (CB) composite-analyte interactions in resistive sensors. These sensors comprise the JPL Electronic Nose (ENose) sensing array developed for monitoring breathing air in human habitats. The polymer in the composite is modeled based on its stereisomerism and sequence isomerism, while the CB is modeled as uncharged naphthalene rings (with no hydrogens). The Dreiding 2.21 force field is used for the polymer and solvent molecules and graphite parameters are assigned to the carbon black atoms. A combination of molecular mechanics (MM) and molecular dynamics (NPT-MD and NVT-MD) techniques are used to obtain the equilibrium composite structure by inserting naphthalene rings in the polymer matrix. Polymers considered for this work include poly(4- vinylphenol), polyethylene oxide, and ethyl cellulose. Analytes studied are representative of both inorganic (ammonia) and organic (methanol, toluene, hydrazine) compounds. The results are analyzed for the composite microstructure by calculating the radial distribution profiles as well as for the sensor response by predicting the interaction energies of the analytes with the composites.

Molecular modeling of polymer composite-analyte interactions in electronic nose sensors

NASA Technical Reports Server (NTRS)

Shevade, A. V.; Ryan, M. A.; Homer, M. L.; Manfreda, A. M.; Zhou, H.; Manatt, K. S.

2003-01-01

We report a molecular modeling study to investigate the polymer-carbon black (CB) composite-analyte interactions in resistive sensors. These sensors comprise the JPL electronic nose (ENose) sensing array developed for monitoring breathing air in human habitats. The polymer in the composite is modeled based on its stereoisomerism and sequence isomerism, while the CB is modeled as uncharged naphthalene rings with no hydrogens. The Dreiding 2.21 force field is used for the polymer, solvent molecules and graphite parameters are assigned to the carbon black atoms. A combination of molecular mechanics (MM) and molecular dynamics (NPT-MD and NVT-MD) techniques are used to obtain the equilibrium composite structure by inserting naphthalene rings in the polymer matrix. Polymers considered for this work include poly(4-vinylphenol), polyethylene oxide, and ethyl cellulose. Analytes studied are representative of both inorganic and organic compounds. The results are analyzed for the composite microstructure by calculating the radial distribution profiles as well as for the sensor response by predicting the interaction energies of the analytes with the composites. c2003 Elsevier Science B.V. All rights reserved.

Molecular Dynamics Visualization (MDV): Stereoscopic 3D Display of Biomolecular Structure and Interactions Using the Unity Game Engine.

PubMed

Wiebrands, Michael; Malajczuk, Chris J; Woods, Andrew J; Rohl, Andrew L; Mancera, Ricardo L

2018-06-21

Molecular graphics systems are visualization tools which, upon integration into a 3D immersive environment, provide a unique virtual reality experience for research and teaching of biomolecular structure, function and interactions. We have developed a molecular structure and dynamics application, the Molecular Dynamics Visualization tool, that uses the Unity game engine combined with large scale, multi-user, stereoscopic visualization systems to deliver an immersive display experience, particularly with a large cylindrical projection display. The application is structured to separate the biomolecular modeling and visualization systems. The biomolecular model loading and analysis system was developed as a stand-alone C# library and provides the foundation for the custom visualization system built in Unity. All visual models displayed within the tool are generated using Unity-based procedural mesh building routines. A 3D user interface was built to allow seamless dynamic interaction with the model while being viewed in 3D space. Biomolecular structure analysis and display capabilities are exemplified with a range of complex systems involving cell membranes, protein folding and lipid droplets.

Coarse-grained models of key self-assembly processes in HIV-1

NASA Astrophysics Data System (ADS)

Grime, John

Computational molecular simulations can elucidate microscopic information that is inaccessible to conventional experimental techniques. However, many processes occur over time and length scales that are beyond the current capabilities of atomic-resolution molecular dynamics (MD). One such process is the self-assembly of the HIV-1 viral capsid, a biological structure that is crucial to viral infectivity. The nucleation and growth of capsid structures requires the interaction of large numbers of capsid proteins within a complicated molecular environment. Coarse-grained (CG) models, where degrees of freedom are removed to produce more computationally efficient models, can in principle access large-scale phenomena such as the nucleation and growth of HIV-1 capsid lattice. We report here studies of the self-assembly behaviors of a CG model of HIV-1 capsid protein, including the influence of the local molecular environment on nucleation and growth processes. Our results suggest a multi-stage process, involving several characteristic structures, eventually producing metastable capsid lattice morphologies that are amenable to subsequent capsid dissociation in order to transmit the viral infection.

Molecular models of alginic acid: Interactions with calcium ions and calcite surfaces

NASA Astrophysics Data System (ADS)

Perry, Thomas D.; Cygan, Randall T.; Mitchell, Ralph

2006-07-01

Cation binding by polysaccharides is observed in many environments and is important for predictive environmental modeling, and numerous industrial and food technology applications. The complexities of these cation-organic interactions are well suited for predictive molecular modeling and the analysis of conformation and configuration of polysaccharides and their influence on cation binding. In this study, alginic acid was chosen as a model polymer system and representative disaccharide and polysaccharide subunits were developed. Molecular dynamics simulation of the torsion angles of the ether linkage between various monomeric subunits identified local and global energy minima for selected disaccharides. The simulations indicate stable disaccharide configurations and a common global energy minimum for all disaccharide models at Φ = 274 ± 7°, Ψ = 227 ± 5°, where Φ and Ψ are the torsion angles about the ether linkage. The ability of disaccharide subunits to bind calcium ions and to associate with the (101¯4) surface of calcite was also investigated. Molecular models of disaccharide interactions with calcite provide binding energy differences for conformations that are related to the proximity and residence densities of the electron-donating moieties with calcium ions on the calcite surface, which are controlled, in part, by the torsion of the ether linkage between monosaccharide units. Dynamically optimized configurations for polymer alginate models with calcium ions were also derived.

A model of lipid-free Apolipoprotein A-I revealed by iterative molecular dynamics simulation

DOE PAGES

Zhang, Xing; Lei, Dongsheng; Zhang, Lei; ...

2015-03-20

Apolipoprotein A-I (apo A-I), the major protein component of high-density lipoprotein, has been proven inversely correlated to cardiovascular risk in past decades. The lipid-free state of apo A-I is the initial stage which binds to lipids forming high-density lipoprotein. Molecular models of lipid-free apo A-I have been reported by methods like X-ray crystallography and chemical cross-linking/mass spectrometry (CCL/MS). Through structural analysis we found that those current models had limited consistency with other experimental results, such as those from hydrogen exchange with mass spectrometry. Through molecular dynamics simulations, we also found those models could not reach a stable equilibrium state. Therefore,more » by integrating various experimental results, we proposed a new structural model for lipidfree apo A-I, which contains a bundled four-helix N-terminal domain (1–192) that forms a variable hydrophobic groove and a mobile short hairpin C-terminal domain (193–243). This model exhibits an equilibrium state through molecular dynamics simulation and is consistent with most of the experimental results known from CCL/MS on lysine pairs, fluorescence resonance energy transfer and hydrogen exchange. This solution-state lipid-free apo A-I model may elucidate the possible conformational transitions of apo A-I binding with lipids in high-density lipoprotein formation.« less

Novel Gbeta Mimic Kelch Proteins Gpb1 and Gpb2 Connect G-Protein Signaling to Ras via Yeast Neurofibromin Homologs Ira 1 and Ira 2: A Model for Human NF1

DTIC Science & Technology

2006-03-01

Introduction Molecular switches composed of G-protein coupled receptors (GPCRs) and associated heterotrimeric G proteins transduce extracellular stimuli...We are investigating the molecular mechanisms by which the Ras GAP activity of the yeast neurofibromin homologs Ira1/2 is regulated as a model to...NF1 (For reviews, see Dasgupta and Gutmann, 2003; Parada, 2000; Zhu and Parada, 2002). It is therefore critical to elucidate the molecular mechanisms

Inhibition of Metalloprotease Botulinum Serotype A from a Pseudo-Peptide Binding Mode to a Small Molecule that is Active in Primary Neurons

DTIC Science & Technology

2007-02-16

a modeled binding mode for inhibitor 2-mercapto-3-phenylpropionyl-RATKML (Ki 330 nM) was generated, and required the use of a molecular dynamic ...2-mercapto-3-phenylpropionyl-RATKML (K(i) = 330 nM) was generated, and required the use of a molecular dynamic conformer of the enzyme displaying the...SiliconGraphicsOctane 2. Insight II (Accelrys, San Diego, CA) was used to build and inspect models. Energy refinement and molecular dynamics were performed using the

Molecular-orbital model for metal-sapphire interfacial strength

NASA Technical Reports Server (NTRS)

Johnson, K. H.; Pepper, S. V.

1982-01-01

Self-consistent-field X-Alpha scattered-wave cluster molecular-orbital models have been constructed for transition and noble metals (Fe, Ni, Cu, and Ag) in contact with a sapphire (Al2O3) surface. It is found that a chemical bond is established between the metal d-orbital electrons and the nonbonding 2p-orbital electrons of the oxygen anions on the Al2O3 surface. An increasing number of occupied metal-sapphire antibonding molecular orbitals explains qualitatively the observed decrease of contact shear strength through the series Fe, Ni, Cu, and Ag.

Metal Hydride and Alkali Halide Opacities in Extrasolar Giant Planets and Cool Stellar Atmospheres

NASA Technical Reports Server (NTRS)

Weck, Philippe F.; Stancil, Phillip C.; Kirby, Kate; Schweitzer, Andreas; Hauschildt, Peter H.

2006-01-01

The lack of accurate and complete molecular line and continuum opacity data has been a serious limitation to developing atmospheric models of cool stars and Extrasolar Giant Planets (EGPs). We report our recent calculations of molecular opacities resulting from the presence of metal hydrides and alkali halides. The resulting data have been included in the PHOENIX stellar atmosphere code (Hauschildt & Baron 1999). The new models, calculated using spherical geometry for all gravities considered, also incorporate our latest database of nearly 670 million molecular lines, and updated equations of state.

Molecular Chemistry as Diagnostic tool for Starbursts and AGNs The Molecular ISM of NGC 4418

NASA Astrophysics Data System (ADS)

Monje, R. R.; Aalto, S.

We present a brief discussion of the statistical surveys of HCN, HNC, HCO+ and HC3N that are used to model the extreme environments in the nuclei of starbursts and AGNs. Molecular studies are particularly useful for probing the deeply enshrouded dusty nuclei of luminous infrared galaxies. Here we present NGC 4418 as an example, one of the closest LIRG with high obscuration of the inner region. The interpretation of the observed line ratios require parallel development of theoretical chemical and radiative transport models.

Computer aided drug design

NASA Astrophysics Data System (ADS)

Jain, A.

2017-08-01

Computer based method can help in discovery of leads and can potentially eliminate chemical synthesis and screening of many irrelevant compounds, and in this way, it save time as well as cost. Molecular modeling systems are powerful tools for building, visualizing, analyzing and storing models of complex molecular structure that can help to interpretate structure activity relationship. The use of various techniques of molecular mechanics and dynamics and software in Computer aided drug design along with statistics analysis is powerful tool for the medicinal chemistry to synthesis therapeutic and effective drugs with minimum side effect.

PSPP: A Protein Structure Prediction Pipeline for Computing Clusters

DTIC Science & Technology

2009-07-01

Evanseck JD, et al. (1998) All-atom empirical potential for molecular modeling and dynamics studies of proteins. Journal of Physical Chemistry B 102...dimensional (3-D) protein structures are critical for the understanding of molecular mechanisms of living systems. Traditionally, X-ray crystallography...disordered proteins are often responsible for molecular recognition, molecular assembly, protein modifica- tion, and entropic chain activities in organisms [26

DEVELOPMENT OF A MODEL THAT CONTAINS BOTH MULTIPOLE MOMENTS AND GAUSSIANS FOR THE CALCULATION OF MOLECULAR ELECTROSTATIC POTENTIALS

EPA Science Inventory

The electrostatic interaction is a critical component of intermolecular interactions in biological processes. Rapid methods for the computation and characterization of the molecular electrostatic potential (MEP) that segment the molecular charge distribution and replace this cont...

Analysis of conjugation of chloramphenicol and hemoglobin by fluorescence, circular dichroism and molecular modeling

NASA Astrophysics Data System (ADS)

Ding, Fei; Liu, Wei; Sun, Ye; Yang, Xin-Ling; Sun, Ying; Zhang, Li

2012-01-01

Chloramphenicol is a low cost, broad spectrum, highly active antibiotic, and widely used in the treatment of serious infections, including typhoid fever and other life-threatening infections of the central nervous system and respiratory tract. The purpose of the present study was to examine the conjugation of chloramphenicol with hemoglobin (Hb) and compared with albumin at molecular level, utilizing fluorescence, UV/vis absorption, circular dichroism (CD) as well as molecular modeling. Fluorescence data indicate that drug bind Hb generate quenching via static mechanism, this corroborates UV/vis absorption measurements that the ground state complex formation with an affinity of 10 4 M -1, and the driving forces in the Hb-drug complex are hydrophilic interactions and hydrogen bonds, as derived from computational model. The accurate binding site of drug has been identified from the analysis of fluorescence and molecular modeling, α1β2 interface of Hb was assigned to possess high-affinity for drug, which located at the β-37 Trp nearby. The structural investigation of the complexed Hb by synchronous fluorescence, UV/vis absorption, and CD observations revealed some degree of Hb structure unfolding upon complexation. Based on molecular modeling, we can draw the conclusion that the binding affinity of drug with albumin is superior, compared with Hb. These phenomena can provide salient information on the absorption, distribution, pharmacology, and toxicity of chloramphenicol and other drugs which have analogous configuration with chloramphenicol.

PHIBSS: MOLECULAR GAS, EXTINCTION, STAR FORMATION, AND KINEMATICS IN THE z = 1.5 STAR-FORMING GALAXY EGS13011166

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

Genzel, R.; Tacconi, L. J.; Kurk, J.

We report matched resolution imaging spectroscopy of the CO 3-2 line (with the IRAM Plateau de Bure millimeter interferometer) and of the H{alpha} line (with LUCI at the Large Binocular Telescope) in the massive z = 1.53 main-sequence galaxy EGS 13011166, as part of the ''Plateau de Bure high-z, blue-sequence survey'' (PHIBSS: Tacconi et al.). We combine these data with Hubble Space Telescope V-I-J-H-band maps to derive spatially resolved distributions of stellar surface density, star formation rate, molecular gas surface density, optical extinction, and gas kinematics. The spatial distribution and kinematics of the ionized and molecular gas are remarkably similarmore » and are well modeled by a turbulent, globally Toomre unstable, rotating disk. The stellar surface density distribution is smoother than the clumpy rest-frame UV/optical light distribution and peaks in an obscured, star-forming massive bulge near the dynamical center. The molecular gas surface density and the effective optical screen extinction track each other and are well modeled by a ''mixed'' extinction model. The inferred slope of the spatially resolved molecular gas to star formation rate relation, N = dlog{Sigma}{sub starform}/dlog{Sigma}{sub molgas}, depends strongly on the adopted extinction model, and can vary from 0.8 to 1.7. For the preferred mixed dust-gas model, we find N = 1.14 {+-} 0.1.« less

A scaling law of radial gas distribution in disk galaxies

NASA Technical Reports Server (NTRS)

Wang, Zhong

1990-01-01

Based on the idea that local conditions within a galactic disk largely determine the region's evolution time scale, researchers built a theoretical model to take into account molecular cloud and star formations in the disk evolution process. Despite some variations that may be caused by spiral arms and central bulge masses, they found that many late-type galaxies show consistency with the model in their radial atomic and molecular gas profiles. In particular, researchers propose that a scaling law be used to generalize the gas distribution characteristics. This scaling law may be useful in helping to understand the observed gas contents in many galaxies. Their model assumes an exponential mass distribution with disk radius. Most of the mass are in atomic gas state at the beginning of the evolution. Molecular clouds form through a modified Schmidt Law which takes into account gravitational instabilities in a possible three-phase structure of diffuse interstellar medium (McKee and Ostriker, 1977; Balbus and Cowie, 1985); whereas star formation proceeds presumably unaffected by the environmental conditions outside of molecular clouds (Young, 1987). In such a model both atomic and molecular gas profiles in a typical galactic disk (as a result of the evolution) can be fitted simultaneously by adjusting the efficiency constants. Galaxies of different sizes and masses, on the other hand, can be compared with the model by simply scaling their characteristic length scales and shifting their radial ranges to match the assumed disk total mass profile sigma tot(r).

Self-assembled squares and triangles by simultaneous hydrogen bonding and metal coordination.

PubMed

Marshall, Laura J; de Mendoza, Javier

2013-04-05

Through the combination of hydrogen bonding and metal-templated self-assembly, molecular squares and molecular triangles are observed in chloroform solution upon the complexation of hydrogen-bonded dimers of para-pyridyl-substituted 2-ureido-4-[1H]-pyrimidinone (UPy) and an appropriate cis-substituted palladium complex. Molecular modeling studies and NMR analysis confirmed the presence of two distinct structures in solution: the tubular structure of the molecular square and propeller-bowl structure of the molecular triangle.

Ordinary differential equations with applications in molecular biology.

PubMed

Ilea, M; Turnea, M; Rotariu, M

2012-01-01

Differential equations are of basic importance in molecular biology mathematics because many biological laws and relations appear mathematically in the form of a differential equation. In this article we presented some applications of mathematical models represented by ordinary differential equations in molecular biology. The vast majority of quantitative models in cell and molecular biology are formulated in terms of ordinary differential equations for the time evolution of concentrations of molecular species. Assuming that the diffusion in the cell is high enough to make the spatial distribution of molecules homogenous, these equations describe systems with many participating molecules of each kind. We propose an original mathematical model with small parameter for biological phospholipid pathway. All the equations system includes small parameter epsilon. The smallness of epsilon is relative to the size of the solution domain. If we reduce the size of the solution region the same small epsilon will result in a different condition number. It is clear that the solution for a smaller region is less difficult. We introduce the mathematical technique known as boundary function method for singular perturbation system. In this system, the small parameter is an asymptotic variable, different from the independent variable. In general, the solutions of such equations exhibit multiscale phenomena. Singularly perturbed problems form a special class of problems containing a small parameter which may tend to zero. Many molecular biology processes can be quantitatively characterized by ordinary differential equations. Mathematical cell biology is a very active and fast growing interdisciplinary area in which mathematical concepts, techniques, and models are applied to a variety of problems in developmental medicine and bioengineering. Among the different modeling approaches, ordinary differential equations (ODE) are particularly important and have led to significant advances. Ordinary differential equations are used to model biological processes on various levels ranging from DNA molecules or biosynthesis phospholipids on the cellular level.

Prediction of triple-charm molecular pentaquarks

NASA Astrophysics Data System (ADS)

Chen, Rui; Hosaka, Atsushi; Liu, Xiang

2017-12-01

In a one-boson-exchange model, we study molecular states of double-charm baryon [Ξc c(3621 )] and a charmed meson (D and D*). Our model indicates that there exist two possible triple-charm molecular pentaquarks, a Ξc cD state with I (JP)=0 (1 /2-), and a Ξc cD* state with I (JP)=0 (3 /2-), and we do not find bound solutions for isotriplet states. In addition, we also extend our formula to explore Ξc cB¯(*), Ξc cD¯(*), and Ξc cB(*) systems and find more possible heavy flavor molecular pentaquarks, a Ξc cB ¯ state with I (JP)=0 (1 /2-), a Ξc cB¯* state with I (JP)=0 (3 /2-), and Ξc cD¯*/Ξc cB* states with I (JP)=0 (1 /2-). Experimental research for these predicted triple-charm molecular pentaquarks is encouraged.

PMG: online generation of high-quality molecular pictures and storyboarded animations

PubMed Central

Autin, Ludovic; Tufféry, Pierre

2007-01-01

The Protein Movie Generator (PMG) is an online service able to generate high-quality pictures and animations for which one can then define simple storyboards. The PMG can therefore efficiently illustrate concepts such as molecular motion or formation/dissociation of complexes. Emphasis is put on the simplicity of animation generation. Rendering is achieved using Dino coupled to POV-Ray. In order to produce highly informative images, the PMG includes capabilities of using different molecular representations at the same time to highlight particular molecular features. Moreover, sophisticated rendering concepts including scene definition, as well as modeling light and materials are available. The PMG accepts Protein Data Bank (PDB) files as input, which may include series of models or molecular dynamics trajectories and produces images or movies under various formats. PMG can be accessed at http://bioserv.rpbs.jussieu.fr/PMG.html. PMID:17478496

Covalent Binding with Neutrons on the Femto-scale

NASA Astrophysics Data System (ADS)

von Oertzen, W.; Kanada-En'yo, Y.; Kimura, M.

2017-06-01

In light nuclei we have well defined clusters, nuclei with closed shells, which serve as centers for binary molecules with covalent binding by valence neutrons. Single neutron orbitals in light neutron-excess nuclei have well defined shell model quantum numbers. With the combination of two clusters and their neutron valence states, molecular two-center orbitals are defined; in the two-center shell model we can place valence neutrons in a large variety of molecular two-center states, and the formation of Dimers becomes possible. The corresponding rotational bands point with their large moments of inertia and the Coriolis decoupling effect (for K = 1/2 bands) to the internal molecular orbital structure in these states. On the basis of these the neutron rich isotopes allow the formation of a large variety molecular structures on the nuclear scale. An extended Ikeda diagram can be drawn for these cases. Molecular bands in Be and Ne-isotopes are discussed as text-book examples.

Early Experiences Porting the NAMD and VMD Molecular Simulation and Analysis Software to GPU-Accelerated OpenPOWER Platforms

PubMed Central

Stone, John E.; Hynninen, Antti-Pekka; Phillips, James C.; Schulten, Klaus

2017-01-01

All-atom molecular dynamics simulations of biomolecules provide a powerful tool for exploring the structure and dynamics of large protein complexes within realistic cellular environments. Unfortunately, such simulations are extremely demanding in terms of their computational requirements, and they present many challenges in terms of preparation, simulation methodology, and analysis and visualization of results. We describe our early experiences porting the popular molecular dynamics simulation program NAMD and the simulation preparation, analysis, and visualization tool VMD to GPU-accelerated OpenPOWER hardware platforms. We report our experiences with compiler-provided autovectorization and compare with hand-coded vector intrinsics for the POWER8 CPU. We explore the performance benefits obtained from unique POWER8 architectural features such as 8-way SMT and its value for particular molecular modeling tasks. Finally, we evaluate the performance of several GPU-accelerated molecular modeling kernels and relate them to other hardware platforms. PMID:29202130

Photoionization-regulated star formation and the structure of molecular clouds

NASA Technical Reports Server (NTRS)

Mckee, Christopher F.

1989-01-01

A model for the rate of low-mass star formation in Galactic molecular clouds and for the influence of this star formation on the structure and evolution of the clouds is presented. The rate of energy injection by newly formed stars is estimated, and the effect of this energy injection on the size of the cloud is determined. It is shown that the observed rate of star formation appears adequate to support the observed clouds against gravitational collapse. The rate of photoionization-regulated star formation is estimated and it is shown to be in agreement with estimates of the observed rate of star formation if the observed molecular cloud parameters are used. The mean cloud extinction and the Galactic star formation rate per unit mass of molecular gas are predicted theoretically from the condition that photionization-regulated star formation be in equilibrium. A simple model for the evolution of isolated molecular clouds is developed.

ls1 mardyn: The Massively Parallel Molecular Dynamics Code for Large Systems.

PubMed

Niethammer, Christoph; Becker, Stefan; Bernreuther, Martin; Buchholz, Martin; Eckhardt, Wolfgang; Heinecke, Alexander; Werth, Stephan; Bungartz, Hans-Joachim; Glass, Colin W; Hasse, Hans; Vrabec, Jadran; Horsch, Martin

2014-10-14

The molecular dynamics simulation code ls1 mardyn is presented. It is a highly scalable code, optimized for massively parallel execution on supercomputing architectures and currently holds the world record for the largest molecular simulation with over four trillion particles. It enables the application of pair potentials to length and time scales that were previously out of scope for molecular dynamics simulation. With an efficient dynamic load balancing scheme, it delivers high scalability even for challenging heterogeneous configurations. Presently, multicenter rigid potential models based on Lennard-Jones sites, point charges, and higher-order polarities are supported. Due to its modular design, ls1 mardyn can be extended to new physical models, methods, and algorithms, allowing future users to tailor it to suit their respective needs. Possible applications include scenarios with complex geometries, such as fluids at interfaces, as well as nonequilibrium molecular dynamics simulation of heat and mass transfer.

A model of early formation of uranium molecular oxides in laser-ablated plasmas

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

Finko, Mikhail S.; Curreli, Davide; Weisz, David G.

Here, in this work, we present a newly constructed U xO y reaction mechanism that consists of 30 reaction channels (21 of which are reversible channels) for 11 uranium molecular species (including ions). Both the selection of reaction channels and calculation of corresponding rate coefficients is accomplished via a comprehensive literature review and application of basic reaction rate theory. The reaction mechanism is supplemented by a detailed description of oxygen plasma chemistry (19 species and 142 reaction channels) and is used to model an atmospheric laser ablated uranium plume via a 0D (global) model. Finally, the global model is usedmore » to analyze the evolution of key uranium molecular species predicted by the reaction mechanism, and the initial stage of formation of uranium oxide species.« less

Energy Minimization of Molecular Features Observed on the (110) Face of Lysozyme Crystals

NASA Technical Reports Server (NTRS)

Perozzo, Mary A.; Konnert, John H.; Li, Huayu; Nadarajah, Arunan; Pusey, Marc

1999-01-01

Molecular dynamics and energy minimization have been carried out using the program XPLOR to check the plausibility of a model lysozyme crystal surface. The molecular features of the (110) face of lysozyme were observed using atomic force microscopy (AFM). A model of the crystal surface was constructed using the PDB file 193L, and was used to simulate an AFM image. Molecule translations, van der Waals radii, and assumed AFM tip shape were adjusted to maximize the correlation coefficient between the experimental and simulated images. The highest degree of 0 correlation (0.92) was obtained with the molecules displaced over 6 A from their positions within the bulk of the crystal. The quality of this starting model, the extent of energy minimization, and the correlation coefficient between the final model and the experimental data will be discussed.

A model of early formation of uranium molecular oxides in laser-ablated plasmas

DOE PAGES

Finko, Mikhail S.; Curreli, Davide; Weisz, David G.; ...

2017-10-12

Here, in this work, we present a newly constructed U xO y reaction mechanism that consists of 30 reaction channels (21 of which are reversible channels) for 11 uranium molecular species (including ions). Both the selection of reaction channels and calculation of corresponding rate coefficients is accomplished via a comprehensive literature review and application of basic reaction rate theory. The reaction mechanism is supplemented by a detailed description of oxygen plasma chemistry (19 species and 142 reaction channels) and is used to model an atmospheric laser ablated uranium plume via a 0D (global) model. Finally, the global model is usedmore » to analyze the evolution of key uranium molecular species predicted by the reaction mechanism, and the initial stage of formation of uranium oxide species.« less

3D-QSAR modeling and molecular docking studies on a series of 2,5 disubstituted 1,3,4-oxadiazoles

NASA Astrophysics Data System (ADS)

Ghaleb, Adib; Aouidate, Adnane; Ghamali, Mounir; Sbai, Abdelouahid; Bouachrine, Mohammed; Lakhlifi, Tahar

2017-10-01

3D-QSAR (comparative molecular field analysis (CoMFA)) and comparative molecular similarity indices analysis (CoMSIA) were performed on novel 2,5 disubstituted 1,3,4-oxadiazoles analogues as anti-fungal agents. The CoMFA and CoMSIA models using 13 compounds in the training set gives Q2 values of 0.52 and 0.51 respectively, while R2 values of 0.92. The adapted alignment method with the suitable parameters resulted in reliable models. The contour maps produced by the CoMFA and CoMSIA models were employed to determine a three-dimensional quantitative structure-activity relationship. Based on this study a set of new molecules with high predicted activities were designed. Surflex-docking confirmed the stability of predicted molecules in the receptor.

Logic circuits based on molecular spider systems.

PubMed

Mo, Dandan; Lakin, Matthew R; Stefanovic, Darko

2016-08-01

Spatial locality brings the advantages of computation speed-up and sequence reuse to molecular computing. In particular, molecular walkers that undergo localized reactions are of interest for implementing logic computations at the nanoscale. We use molecular spider walkers to implement logic circuits. We develop an extended multi-spider model with a dynamic environment wherein signal transmission is triggered via localized reactions, and use this model to implement three basic gates (AND, OR, NOT) and a cascading mechanism. We develop an algorithm to automatically generate the layout of the circuit. We use a kinetic Monte Carlo algorithm to simulate circuit computations, and we analyze circuit complexity: our design scales linearly with formula size and has a logarithmic time complexity. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Nonlinear vibrational excitations in molecular crystals molecular mechanics calculations

NASA Astrophysics Data System (ADS)

Pumilia, P.; Abbate, S.; Baldini, G.; Ferro, D. R.; Tubino, R.

1992-03-01

The coupling constant for vibrational solitons χ has been examined in a molecular mechanics model for acetanilide (ACN) molecular crystal. According to A.C. Scott, solitons can form and propagate in solid acetanilide over a threshold energy value. This can be regarded as a structural model for the spines of hydrogen bond chains stabilizing the α helical structure of proteins. A one dimensional hydrogen bond chain of ACN has been built, for which we have found that, even though experimental parameters are correctly predicted, the excessive rigidity of the isolated chain prevents the formation of a localized distortion around the excitation. Yet, C=O coupling value with softer lattice modes could be rather high, allowing self-trapping to take place.

Rhabdomyosarcomas: an overview on the experimental animal models.

PubMed

Zanola, Alessandra; Rossi, Stefania; Faggi, Fiorella; Monti, Eugenio; Fanzani, Alessandro

2012-07-01

Rhabdomyosarcomas (RMS) are aggressive childhood soft-tissue malignancies deriving from mesenchymal progenitors that are committed to muscle-specific lineages. Despite the histopathological signatures associated with three main histological variants, termed embryonal, alveolar and pleomorphic, a plethora of genetic and molecular changes are recognized in RMS. Over the years, exposure to carcinogens or ionizing radiations and gene-targeting approaches in vivo have greatly contributed to disclose some of the mechanisms underlying RMS onset. In this review, we describe the principal distinct features associated with RMS variants and focus on the current available experimental animal models to point out the molecular determinants cooperating with RMS development and progression. © 2012 The Authors Journal of Cellular and Molecular Medicine © 2012 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.

Studying plant-pathogen interactions in the genomics era: beyond molecular Koch’s postulates to systems biology

USDA-ARS?s Scientific Manuscript database

Molecular factors enabling microbial pathogens to cause plant diseases have been sought with increasing efficacy over three research eras, which successively introduced the tools of disease physiology, single-gene molecular genetics, and genomics. From this work emerged a unified model of the intera...

Empirical Refinements of a Molecular Genetics Learning Progression: The Molecular Constructs

ERIC Educational Resources Information Center

Todd, Amber; Kenyon, Lisa

2016-01-01

This article describes revisions to four of the eight constructs of the Duncan molecular genetics learning progression [Duncan, Rogat, & Yarden, (2009)]. As learning progressions remain hypothetical models until validated by multiple rounds of empirical studies, these revisions are an important step toward validating the progression. Our…

Simulation of aerosol flow interaction with a solid body on molecular level

NASA Astrophysics Data System (ADS)

Amelyushkin, Ivan A.; Stasenko, Albert L.

2018-05-01

Physico-mathematical models and numerical algorithm of two-phase flow interaction with a solid body are developed. Results of droplet motion and its impingement upon a rough surface in real gas boundary layer simulation on the molecular level obtained via molecular dynamics technique are presented.

A computational chemistry perspective on the current status and future direction of hepatitis B antiviral drug discovery.

PubMed

Morgnanesi, Dante; Heinrichs, Eric J; Mele, Anthony R; Wilkinson, Sean; Zhou, Suzanne; Kulp, John L

2015-11-01

Computational chemical biology, applied to research on hepatitis B virus (HBV), has two major branches: bioinformatics (statistical models) and first-principle methods (molecular physics). While bioinformatics focuses on statistical tools and biological databases, molecular physics uses mathematics and chemical theory to study the interactions of biomolecules. Three computational techniques most commonly used in HBV research are homology modeling, molecular docking, and molecular dynamics. Homology modeling is a computational simulation to predict protein structure and has been used to construct conformers of the viral polymerase (reverse transcriptase domain and RNase H domain) and the HBV X protein. Molecular docking is used to predict the most likely orientation of a ligand when it is bound to a protein, as well as determining an energy score of the docked conformation. Molecular dynamics is a simulation that analyzes biomolecule motions and determines conformation and stability patterns. All of these modeling techniques have aided in the understanding of resistance mutations on HBV non-nucleos(t)ide reverse-transcriptase inhibitor binding. Finally, bioinformatics can be used to study the DNA and RNA protein sequences of viruses to both analyze drug resistance and to genotype the viral genomes. Overall, with these techniques, and others, computational chemical biology is becoming more and more necessary in hepatitis B research. This article forms part of a symposium in Antiviral Research on "An unfinished story: from the discovery of the Australia antigen to the development of new curative therapies for hepatitis B." Copyright © 2015 Elsevier B.V. All rights reserved.

Charge Transport Processes in Molecular Junctions

NASA Astrophysics Data System (ADS)

Smith, Christopher Eugene

Molecular electronics (ME) has evolved into a rich area of exploration that combines the fields of chemistry, materials, electronic engineering and computational modeling to explore the physics behind electronic conduction at the molecular level. Through studying charge transport properties of single molecules and nanoscale molecular materials the field has gained the potential to bring about new avenues for the miniaturization of electrical components where quantum phenomena are utilized to achieve solid state molecular device functionality. Molecular junctions are platforms that enable these studies and consist of a single molecule or a small group of molecules directly connected to electrodes. The work presented in this thesis has built upon the current understanding of the mechanisms of charge transport in ordered junctions using self-assembled monolayer (SAM) molecular thin films. Donor and acceptor compounds were synthesized and incorporated into SAMs grown on metal substrates then the transport properties were measured with conducting probe atomic force microscopy (CP-AFM). In addition to experimentally measured current-voltage (I-V) curves, the transport properties were addressed computationally and modeled theoretically. The key objectives of this project were to 1) investigate the impact of molecular structure on hole and electron charge transport, 2) understand the nature of the charge carriers and their structure-transport properties through long (<4 nm) conjugated molecular wires, and 3) quantitatively extract interfacial properties characteristic to macroscopic junctions, such as energy level alignment and molecule-contact electronic coupling from experimental I-V curves. Here, we lay ground work for creating a more complete picture of charge transport in macroscopically ordered molecular junctions of controlled architecture, length and charge carrier. The polaronic nature of hopping transport has been predicted in long, conjugated molecular wires. Using quantum-based calculations, we modeled 'p-type' polaron transport through oligophenylenethiophene (OPTI) wires and assigned transport activation energies to specific modes of nuclear motion. We also show control over 'n-type', LUMO-mediated transport in short ( 2 nm) redox-active perylenediimide (PDI) SAMs bound to contacts through isocyano linkers. By changing the contact work function (φ) and temperature, we were able to verify thermally-assisted LUMO transport. Transition voltage spectroscopy and the single level model was employed to fit the experimental I-V curves and extract the electronic coupling (epsilon) and the EF-LUMO offset (epsilonl). It was found that epsilonl does not change with φ (LUMO pinning), while Gamma changes with both φ and temperature. Further, the PDI SAMs could be reversibly chemically gated to modulate the transport. These results help advance our understanding of transport behavior in semiconducting molecular thin films, and open opportunities to engineer improved electronic functionality into molecular devices.

Hybrid Molecular and Spin-Semiconductor Based Research

DTIC Science & Technology

2005-02-02

thick layers of low- temperature-grown (LTG) GaAs, i.e. GaAs grown at lower than normal substrate temperatures in a molecular beam epitaxy system...1999 – Oct.31, 2004 4. TITLE AND SUBTITLE Hybrid Molecular and Spin-Semiconductor Based research 5. FUNDING NUMBERS DAAD19-99-1-0198...spintronic devices. Thrust III is entitled “ Molecular Electronics” and its objective is to develop, characterize and model organic/inorganic

Molecular Population Genetics

PubMed Central

Casillas, Sònia; Barbadilla, Antonio

2017-01-01

Molecular population genetics aims to explain genetic variation and molecular evolution from population genetics principles. The field was born 50 years ago with the first measures of genetic variation in allozyme loci, continued with the nucleotide sequencing era, and is currently in the era of population genomics. During this period, molecular population genetics has been revolutionized by progress in data acquisition and theoretical developments. The conceptual elegance of the neutral theory of molecular evolution or the footprint carved by natural selection on the patterns of genetic variation are two examples of the vast number of inspiring findings of population genetics research. Since the inception of the field, Drosophila has been the prominent model species: molecular variation in populations was first described in Drosophila and most of the population genetics hypotheses were tested in Drosophila species. In this review, we describe the main concepts, methods, and landmarks of molecular population genetics, using the Drosophila model as a reference. We describe the different genetic data sets made available by advances in molecular technologies, and the theoretical developments fostered by these data. Finally, we review the results and new insights provided by the population genomics approach, and conclude by enumerating challenges and new lines of inquiry posed by increasingly large population scale sequence data. PMID:28270526

Molecular Population Genetics.

PubMed

Casillas, Sònia; Barbadilla, Antonio

2017-03-01

Molecular population genetics aims to explain genetic variation and molecular evolution from population genetics principles. The field was born 50 years ago with the first measures of genetic variation in allozyme loci, continued with the nucleotide sequencing era, and is currently in the era of population genomics. During this period, molecular population genetics has been revolutionized by progress in data acquisition and theoretical developments. The conceptual elegance of the neutral theory of molecular evolution or the footprint carved by natural selection on the patterns of genetic variation are two examples of the vast number of inspiring findings of population genetics research. Since the inception of the field, Drosophila has been the prominent model species: molecular variation in populations was first described in Drosophila and most of the population genetics hypotheses were tested in Drosophila species. In this review, we describe the main concepts, methods, and landmarks of molecular population genetics, using the Drosophila model as a reference. We describe the different genetic data sets made available by advances in molecular technologies, and the theoretical developments fostered by these data. Finally, we review the results and new insights provided by the population genomics approach, and conclude by enumerating challenges and new lines of inquiry posed by increasingly large population scale sequence data. Copyright © 2017 Casillas and Barbadilla.

Comparing Classical Water Models Using Molecular Dynamics to Find Bulk Properties

ERIC Educational Resources Information Center

Kinnaman, Laura J.; Roller, Rachel M.; Miller, Carrie S.

2018-01-01

A computational chemistry exercise for the undergraduate physical chemistry laboratory is described. In this exercise, students use the molecular dynamics package Amber to generate trajectories of bulk liquid water for 4 different water models (TIP3P, OPC, SPC/E, and TIP4Pew). Students then process the trajectory to calculate structural (radial…

Computational Nanotechnology of Molecular Materials, Electronics and Machines

NASA Technical Reports Server (NTRS)

Srivastava, D.; Biegel, Bryan A. (Technical Monitor)

2002-01-01

This viewgraph presentation covers carbon nanotubes, their characteristics, and their potential future applications. The presentation include predictions on the development of nanostructures and their applications, the thermal characteristics of carbon nanotubes, mechano-chemical effects upon carbon nanotubes, molecular electronics, and models for possible future nanostructure devices. The presentation also proposes a neural model for signal processing.

Examination of Bond Properties through Infrared Spectroscopy and Molecular Modeling in the General Chemistry Laboratory

ERIC Educational Resources Information Center

Csizmar, Clifford M.; Force, Dee Ann; Warner, Don L.

2012-01-01

A concerted effort has been made to increase the opportunities for undergraduate students to address scientific problems employing the processes used by practicing chemists. As part of this effort, an infrared (IR) spectroscopy and molecular modeling experiment was developed for the first-year general chemistry laboratory course. In the…

A Learner-Centered Molecular Modeling Exercise for Allied Health Majors in a Biochemistry Class

ERIC Educational Resources Information Center

Fletcher, Terace M.; Ershler, Jeff

2014-01-01

Learner-centered molecular modeling exercises in college science courses can be especially challenging for nonchemistry majors as students typically have a higher degree of anxiety and may not appreciate the relevance of the work. This article describes a learner-centered project given to allied health majors in a Biochemistry course. The project…

Computational Model of a Positive BDNF Feedback Loop in Hippocampal Neurons Following Inhibitory Avoidance Training

ERIC Educational Resources Information Center

Zhang, Yili; Smolen, Paul; Alberini, Cristina M.; Baxter, Douglas A.; Byrne, John H.

2016-01-01

Inhibitory avoidance (IA) training in rodents initiates a molecular cascade within hippocampal neurons. This cascade contributes to the transition of short- to long-term memory (i.e., consolidation). Here, a differential equation-based model was developed to describe a positive feedback loop within this molecular cascade. The feedback loop begins…

Molecular Modeling of Heme Proteins Using MOE: Bio-Inorganic and Structure-Function Activity for Undergraduates

ERIC Educational Resources Information Center

Ray, Gigi B.; Cook, J. Whitney

2005-01-01

A biochemical molecular modeling project on heme proteins suitable for an introductory Biochemistry I class has been designed with a 2-fold objective: i) to reinforce the correlation between protein three-dimensional structure and function through a discovery oriented project, and ii) to introduce students to the fields of bioinorganic and…

Biological intuition in alignment-free methods: response to Posada.

PubMed

Ragan, Mark A; Chan, Cheong Xin

2013-08-01

A recent editorial in Journal of Molecular Evolution highlights opportunities and challenges facing molecular evolution in the era of next-generation sequencing. Abundant sequence data should allow more-complex models to be fit at higher confidence, making phylogenetic inference more reliable and improving our understanding of evolution at the molecular level. However, concern that approaches based on multiple sequence alignment may be computationally infeasible for large datasets is driving the development of so-called alignment-free methods for sequence comparison and phylogenetic inference. The recent editorial characterized these approaches as model-free, not based on the concept of homology, and lacking in biological intuition. We argue here that alignment-free methods have not abandoned models or homology, and can be biologically intuitive.

Molecular modeling of polycarbonate materials: Glass transition and mechanical properties

NASA Astrophysics Data System (ADS)

Palczynski, Karol; Wilke, Andreas; Paeschke, Manfred; Dzubiella, Joachim

2017-09-01

Linking the experimentally accessible macroscopic properties of thermoplastic polymers to their microscopic static and dynamic properties is a key requirement for targeted material design. Classical molecular dynamics simulations enable us to study the structural and dynamic behavior of molecules on microscopic scales, and statistical physics provides a framework for relating these properties to the macroscopic properties. We take a first step toward creating an automated workflow for the theoretical prediction of thermoplastic material properties by developing an expeditious method for parameterizing a simple yet surprisingly powerful coarse-grained bisphenol-A polycarbonate model which goes beyond previous coarse-grained models and successfully reproduces the thermal expansion behavior, the glass transition temperature as a function of the molecular weight, and several elastic properties.

Modeling Photodetachment from HO2- Using the pd Case of the Generalized Mixed Character Molecular Orbital Model

NASA Astrophysics Data System (ADS)

Blackstone, Christopher C.; Sanov, Andrei

2016-06-01

Using the generalized model for photodetachment of electrons from mixed-character molecular orbitals, we gain insight into the nature of the HOMO of HO2- by treating it as a coherent superpostion of one p- and one d-type atomic orbital. Fitting the pd model function to the ab initio calculated HOMO of HO2- yields a fractional d-character, γp, of 0.979. The modeled curve of the anisotropy parameter, β, as a function of electron kinetic energy for a pd-type mixed character orbital is matched to the experimental data.

Electrospray-assisted encapsulation of caffeine in alginate microhydrogels.

PubMed

Nikoo, Alireza Mehregan; Kadkhodaee, Rassoul; Ghorani, Behrouz; Razzaq, Hussam; Tucker, Nick

2018-05-02

One of the major challenges with microencapsulation and delivery of low molecular weight bioactive compounds is their diffusional loss during storage and process conditions as well as under gastric conditions. In an attempt to slow down the release rate of core material, electrospray fabricated calcium alginate microhydrogels were coated with low molecular weight and high molecular weight chitosans. Caffeine as a hydrophilic model compound was used due to its several advantages on human behavior especially increasing consciousness. Mathematical modeling of the caffeine release by fitting the data with Korsmeyer-Peppas model showed that Fick's diffusion law could be the prevalent mechanism of the release. Electrostatic interaction between alginate and chitosan (particularly in the presence of 1% low molecular weight chitosan) provided an effective barrier against caffeine release and significantly reduced swelling of particles compared to control samples. The results of this study demonstrated that calcium alginate microhydrogels coated by chitosan could be used for encapsulation of low molecular compounds. However, more complementary research must be done in this field. In addition, electrospray, by producing monodisperse particles, would be as an alternative method for fabrication of microparticles based on natural polymers. Copyright © 2018. Published by Elsevier B.V.

The Holographic Electron Density Theorem, de-quantization, re-quantization, and nuclear charge space extrapolations of the Universal Molecule Model

NASA Astrophysics Data System (ADS)

Mezey, Paul G.

2017-11-01

Two strongly related theorems on non-degenerate ground state electron densities serve as the basis of "Molecular Informatics". The Hohenberg-Kohn theorem is a statement on global molecular information, ensuring that the complete electron density contains the complete molecular information. However, the Holographic Electron Density Theorem states more: the local information present in each and every positive volume density fragment is already complete: the information in the fragment is equivalent to the complete molecular information. In other words, the complete molecular information provided by the Hohenberg-Kohn Theorem is already provided, in full, by any positive volume, otherwise arbitrarily small electron density fragment. In this contribution some of the consequences of the Holographic Electron Density Theorem are discussed within the framework of the "Nuclear Charge Space" and the Universal Molecule Model. In the Nuclear Charge Space" the nuclear charges are regarded as continuous variables, and in the more general Universal Molecule Model some other quantized parameteres are also allowed to become "de-quantized and then re-quantized, leading to interrelations among real molecules through abstract molecules. Here the specific role of the Holographic Electron Density Theorem is discussed within the above context.

The application of molecular topology for ulcerative colitis drug discovery.

PubMed

Bellera, Carolina L; Di Ianni, Mauricio E; Talevi, Alan

2018-01-01

Although the therapeutic arsenal against ulcerative colitis has greatly expanded (including the revolutionary advent of biologics), there remain patients who are refractory to current medications while the safety of the available therapeutics could also be improved. Molecular topology provides a theoretic framework for the discovery of new therapeutic agents in a very efficient manner, and its applications in the field of ulcerative colitis have slowly begun to flourish. Areas covered: After discussing the basics of molecular topology, the authors review QSAR models focusing on validated targets for the treatment of ulcerative colitis, entirely or partially based on topological descriptors. Expert opinion: The application of molecular topology to ulcerative colitis drug discovery is still very limited, and many of the existing reports seem to be strictly theoretic, with no experimental validation or practical applications. Interestingly, mechanism-independent models based on phenotypic responses have recently been reported. Such models are in agreement with the recent interest raised by network pharmacology as a potential solution for complex disorders. These and other similar studies applying molecular topology suggest that some therapeutic categories may present a 'topological pattern' that goes beyond a specific mechanism of action.

Molecular Characterization of Growth Hormone-producing Tumors in the GC Rat Model of Acromegaly.

PubMed

Martín-Rodríguez, Juan F; Muñoz-Bravo, Jose L; Ibañez-Costa, Alejandro; Fernandez-Maza, Laura; Balcerzyk, Marcin; Leal-Campanario, Rocío; Luque, Raúl M; Castaño, Justo P; Venegas-Moreno, Eva; Soto-Moreno, Alfonso; Leal-Cerro, Alfonso; Cano, David A

2015-11-09

Acromegaly is a disorder resulting from excessive production of growth hormone (GH) and consequent increase of insulin-like growth factor 1 (IGF-I), most frequently caused by pituitary adenomas. Elevated GH and IGF-I levels results in wide range of somatic, cardiovascular, endocrine, metabolic, and gastrointestinal morbidities. Subcutaneous implantation of the GH-secreting GC cell line in rats leads to the formation of tumors. GC tumor-bearing rats develop characteristics that resemble human acromegaly including gigantism and visceromegaly. However, GC tumors remain poorly characterized at a molecular level. In the present work, we report a detailed histological and molecular characterization of GC tumors using immunohistochemistry, molecular biology and imaging techniques. GC tumors display histopathological and molecular features of human GH-producing tumors, including hormone production, cell architecture, senescence activation and alterations in cell cycle gene expression. Furthermore, GC tumors cells displayed sensitivity to somatostatin analogues, drugs that are currently used in the treatment of human GH-producing adenomas, thus supporting the GC tumor model as a translational tool to evaluate therapeutic agents. The information obtained would help to maximize the usefulness of the GC rat model for research and preclinical studies in GH-secreting tumors.

Molecular Characterization of Growth Hormone-producing Tumors in the GC Rat Model of Acromegaly

PubMed Central

Martín-Rodríguez, Juan F.; Muñoz-Bravo, Jose L.; Ibañez-Costa, Alejandro; Fernandez-Maza, Laura; Balcerzyk, Marcin; Leal-Campanario, Rocío; Luque, Raúl M.; Castaño, Justo P.; Venegas-Moreno, Eva; Soto-Moreno, Alfonso; Leal-Cerro, Alfonso; Cano, David A.

2015-01-01

Acromegaly is a disorder resulting from excessive production of growth hormone (GH) and consequent increase of insulin-like growth factor 1 (IGF-I), most frequently caused by pituitary adenomas. Elevated GH and IGF-I levels results in wide range of somatic, cardiovascular, endocrine, metabolic, and gastrointestinal morbidities. Subcutaneous implantation of the GH-secreting GC cell line in rats leads to the formation of tumors. GC tumor-bearing rats develop characteristics that resemble human acromegaly including gigantism and visceromegaly. However, GC tumors remain poorly characterized at a molecular level. In the present work, we report a detailed histological and molecular characterization of GC tumors using immunohistochemistry, molecular biology and imaging techniques. GC tumors display histopathological and molecular features of human GH-producing tumors, including hormone production, cell architecture, senescence activation and alterations in cell cycle gene expression. Furthermore, GC tumors cells displayed sensitivity to somatostatin analogues, drugs that are currently used in the treatment of human GH-producing adenomas, thus supporting the GC tumor model as a translational tool to evaluate therapeutic agents. The information obtained would help to maximize the usefulness of the GC rat model for research and preclinical studies in GH-secreting tumors. PMID:26549306

Chemically specific coarse-grained models to investigate the structure of biomimetic membranes

DOE PAGES

Kowalik, Ma?gorzata; Schantz, Allen B.; Naqi, Abdullah; ...

2017-11-29

Biomimetic polymer/protein membranes are promising materials for DNA sequencing, sensors, drug delivery and water purification. These self-assembled structures are made from low molecular weight amphiphilic block copolymers (N hydrophobic < 40 for a diblock copolymer), including poly(ethylene oxide)–1,2-polybutadiene (EO–1,2-BD) and poly(ethylene oxide)–poly(ethyl ethylene) (EO–EE). To examine these membranes' nanoscale structure, we developed a coarse-grained molecular dynamics (CG MD) model for EO–1,2-BD and assembled a CG MD model for EO–EE using parameters from two published force fields. We observe that the polymers' hydrophobic core blocks are slightly stretched compared to the random coil configuration seen at higher molecular weights. We alsomore » observe an increase in the interdigitation of the hydrophobic leaflets with increasing molecular weight (consistent with literature). The hydration level of the EO corona (which may influence protein incorporation) is higher for membranes with a larger area/chain, regardless of whether EE or 1,2-BD forms the hydrophobic block. Our results provide a molecular-scale view of membrane packing and hydrophobicity, two important properties for creating polymer–protein biomimetic membranes.« less

Chemically specific coarse-grained models to investigate the structure of biomimetic membranes

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

Kowalik, Ma?gorzata; Schantz, Allen B.; Naqi, Abdullah

Biomimetic polymer/protein membranes are promising materials for DNA sequencing, sensors, drug delivery and water purification. These self-assembled structures are made from low molecular weight amphiphilic block copolymers (N hydrophobic < 40 for a diblock copolymer), including poly(ethylene oxide)–1,2-polybutadiene (EO–1,2-BD) and poly(ethylene oxide)–poly(ethyl ethylene) (EO–EE). To examine these membranes' nanoscale structure, we developed a coarse-grained molecular dynamics (CG MD) model for EO–1,2-BD and assembled a CG MD model for EO–EE using parameters from two published force fields. We observe that the polymers' hydrophobic core blocks are slightly stretched compared to the random coil configuration seen at higher molecular weights. We alsomore » observe an increase in the interdigitation of the hydrophobic leaflets with increasing molecular weight (consistent with literature). The hydration level of the EO corona (which may influence protein incorporation) is higher for membranes with a larger area/chain, regardless of whether EE or 1,2-BD forms the hydrophobic block. Our results provide a molecular-scale view of membrane packing and hydrophobicity, two important properties for creating polymer–protein biomimetic membranes.« less

Development of molecular closures for the reference interaction site model theory with application to square-well and Lennard-Jones homonuclear diatomics.

PubMed

Munaò, Gianmarco; Costa, Dino; Caccamo, Carlo

2016-10-19

Inspired by significant improvements obtained for the performances of the polymer reference interaction site model (PRISM) theory of the fluid phase when coupled with 'molecular closures' (Schweizer and Yethiraj 1993 J. Chem. Phys. 98 9053), we exploit a matrix generalization of this concept, suitable for the more general RISM framework. We report a preliminary test of the formalism, as applied to prototype square-well homonuclear diatomics. As for the structure, comparison with Monte Carlo shows that molecular closures are slightly more predictive than their 'atomic' counterparts, and thermodynamic properties are equally accurate. We also devise an application of molecular closures to models interacting via continuous, soft-core potentials, by using well established prescriptions in liquid state perturbation theories. In the case of Lennard-Jones dimers, our scheme definitely improves over the atomic one, providing semi-quantitative structural results, and quite good estimates of internal energy, pressure and phase coexistence. Our finding paves the way to a systematic employment of molecular closures within the RISM framework to be applied to more complex systems, such as molecules constituted by several non-equivalent interaction sites.

Hidden Markov models and other machine learning approaches in computational molecular biology

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

Baldi, P.

1995-12-31

This tutorial was one of eight tutorials selected to be presented at the Third International Conference on Intelligent Systems for Molecular Biology which was held in the United Kingdom from July 16 to 19, 1995. Computational tools are increasingly needed to process the massive amounts of data, to organize and classify sequences, to detect weak similarities, to separate coding from non-coding regions, and reconstruct the underlying evolutionary history. The fundamental problem in machine learning is the same as in scientific reasoning in general, as well as statistical modeling: to come up with a good model for the data. In thismore » tutorial four classes of models are reviewed. They are: Hidden Markov models; artificial Neural Networks; Belief Networks; and Stochastic Grammars. When dealing with DNA and protein primary sequences, Hidden Markov models are one of the most flexible and powerful alignments and data base searches. In this tutorial, attention is focused on the theory of Hidden Markov Models, and how to apply them to problems in molecular biology.« less

Animal models for rotator cuff repair.

PubMed

Lebaschi, Amir; Deng, Xiang-Hua; Zong, Jianchun; Cong, Guang-Ting; Carballo, Camila B; Album, Zoe M; Camp, Christopher; Rodeo, Scott A

2016-11-01

Rotator cuff (RC) injuries represent a significant source of pain, functional impairment, and morbidity. The large disease burden of RC pathologies necessitates rapid development of research methodologies to treat these conditions. Given their ability to model anatomic, biomechanical, cellular, and molecular aspects of the human RC, animal models have played an indispensable role in reducing injury burden and advancing this field of research for many years. The development of animal models in the musculoskeletal (MSK) research arena is uniquely different from that in other fields in that the similarity of macrostructures and functions is as critical to replicate as cellular and molecular functions. Traditionally, larger animals have been used because of their anatomic similarity to humans and the ease of carrying out realistic surgical procedures. However, refinement of current molecular methods, introduction of novel research tools, and advancements in microsurgical techniques have increased the applicability of small animal models in MSK research. In this paper, we review RC animal models and emphasize a murine model that may serve as a valuable instrument for future RC tendon repair investigations. © 2016 New York Academy of Sciences.

An Estimation of Hybrid Quantum Mechanical Molecular Mechanical Polarization Energies for Small Molecules Using Polarizable Force-Field Approaches

DOE PAGES

Huang, Jing; Mei, Ye; König, Gerhard; ...

2017-01-24

Here in this work, we report two polarizable molecular mechanics (polMM) force field models for estimating the polarization energy in hybrid quantum mechanical molecular mechanical (QM/MM) calculations. These two models, named the potential of atomic charges (PAC) and potential of atomic dipoles (PAD), are formulated from the ab initio quantum mechanical (QM) response kernels for the prediction of the QM density response to an external molecular mechanical (MM) environment (as described by external point charges). The PAC model is similar to fluctuating charge (FQ) models because the energy depends on external electrostatic potential values at QM atomic sites; the PADmore » energy depends on external electrostatic field values at QM atomic sites, resembling induced dipole (ID) models. To demonstrate their uses, we apply the PAC and PAD models to 12 small molecules, which are solvated by TIP3P water. The PAC model reproduces the QM/MM polarization energy with a R 2 value of 0.71 for aniline (in 10,000 TIP3P water configurations) and 0.87 or higher for other eleven solute molecules, while the PAD model has a much better performance with R 2 values of 0.98 or higher. The PAC model reproduces reference QM/MM hydration free energies for 12 solute molecules with a RMSD of 0.59 kcal/mol. The PAD model is even more accurate, with a much smaller RMSD of 0.12 kcal/mol, with respect to the reference. Lastly, this suggests that polarization effects, including both local charge distortion and intramolecular charge transfer, can be well captured by induced dipole type models with proper parametrization.« less

An Estimation of Hybrid Quantum Mechanical Molecular Mechanical Polarization Energies for Small Molecules Using Polarizable Force-Field Approaches.

PubMed

Huang, Jing; Mei, Ye; König, Gerhard; Simmonett, Andrew C; Pickard, Frank C; Wu, Qin; Wang, Lee-Ping; MacKerell, Alexander D; Brooks, Bernard R; Shao, Yihan

2017-02-14

In this work, we report two polarizable molecular mechanics (polMM) force field models for estimating the polarization energy in hybrid quantum mechanical molecular mechanical (QM/MM) calculations. These two models, named the potential of atomic charges (PAC) and potential of atomic dipoles (PAD), are formulated from the ab initio quantum mechanical (QM) response kernels for the prediction of the QM density response to an external molecular mechanical (MM) environment (as described by external point charges). The PAC model is similar to fluctuating charge (FQ) models because the energy depends on external electrostatic potential values at QM atomic sites; the PAD energy depends on external electrostatic field values at QM atomic sites, resembling induced dipole (ID) models. To demonstrate their uses, we apply the PAC and PAD models to 12 small molecules, which are solvated by TIP3P water. The PAC model reproduces the QM/MM polarization energy with a R 2 value of 0.71 for aniline (in 10,000 TIP3P water configurations) and 0.87 or higher for other 11 solute molecules, while the PAD model has a much better performance with R 2 values of 0.98 or higher. The PAC model reproduces reference QM/MM hydration free energies for 12 solute molecules with a RMSD of 0.59 kcal/mol. The PAD model is even more accurate, with a much smaller RMSD of 0.12 kcal/mol, with respect to the reference. This suggests that polarization effects, including both local charge distortion and intramolecular charge transfer, can be well captured by induced dipole type models with proper parametrization.

An Estimation of Hybrid Quantum Mechanical Molecular Mechanical Polarization Energies for Small Molecules Using Polarizable Force-Field Approaches

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

Huang, Jing; Mei, Ye; König, Gerhard

Here in this work, we report two polarizable molecular mechanics (polMM) force field models for estimating the polarization energy in hybrid quantum mechanical molecular mechanical (QM/MM) calculations. These two models, named the potential of atomic charges (PAC) and potential of atomic dipoles (PAD), are formulated from the ab initio quantum mechanical (QM) response kernels for the prediction of the QM density response to an external molecular mechanical (MM) environment (as described by external point charges). The PAC model is similar to fluctuating charge (FQ) models because the energy depends on external electrostatic potential values at QM atomic sites; the PADmore » energy depends on external electrostatic field values at QM atomic sites, resembling induced dipole (ID) models. To demonstrate their uses, we apply the PAC and PAD models to 12 small molecules, which are solvated by TIP3P water. The PAC model reproduces the QM/MM polarization energy with a R 2 value of 0.71 for aniline (in 10,000 TIP3P water configurations) and 0.87 or higher for other eleven solute molecules, while the PAD model has a much better performance with R 2 values of 0.98 or higher. The PAC model reproduces reference QM/MM hydration free energies for 12 solute molecules with a RMSD of 0.59 kcal/mol. The PAD model is even more accurate, with a much smaller RMSD of 0.12 kcal/mol, with respect to the reference. Lastly, this suggests that polarization effects, including both local charge distortion and intramolecular charge transfer, can be well captured by induced dipole type models with proper parametrization.« less