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1

Modeling of solvent-dependent conformational transitions in Burkholderia cepacia lipase  

PubMed Central

Background The characteristic of most lipases is the interfacial activation at a lipid interface or in non-polar solvents. Interfacial activation is linked to a large conformational change of a lid, from a closed to an open conformation which makes the active site accessible for substrates. While for many lipases crystal structures of the closed and open conformation have been determined, the pathway of the conformational transition and possible bottlenecks are unknown. Therefore, molecular dynamics simulations of a closed homology model and an open crystal structure of Burkholderia cepacia lipase in water and toluene were performed to investigate the influence of solvents on structure, dynamics, and the conformational transition of the lid. Results The conformational transition of B. cepacia lipase was dependent on the solvent. In simulations of closed B. cepacia lipase in water no conformational transition was observed, while in three independent simulations of the closed lipase in toluene the lid gradually opened during the first 10–15 ns. The pathway of conformational transition was accessible and a barrier was identified, where a helix prevented the lid from opening to the completely open conformation. The open structure in toluene was stabilized by the formation of hydrogen bonds. In simulations of open lipase in water, the lid closed slowly during 30 ns nearly reaching its position in the closed crystal structure, while a further lid opening compared to the crystal structure was observed in toluene. While the helical structure of the lid was intact during opening in toluene, it partially unfolded upon closing in water. The closing of the lid in water was also observed, when with eight intermediate structures between the closed and the open conformation as derived from the simulations in toluene were taken as starting structures. A hydrophobic ?-hairpin was moving away from the lid in all simulations in water, which was not observed in simulations in toluene. The conformational transition of the lid was not correlated to the motions of the ?-hairpin structure. Conclusion Conformational transitions between the experimentally observed closed and open conformation of the lid were observed by multiple molecular dynamics simulations of B. cepacia lipase. Transitions in both directions occurred without applying restraints or external forces. The opening and closing were driven by the solvent and independent of a bound substrate molecule.

Trodler, Peter; Schmid, Rolf D; Pleiss, Jurgen

2009-01-01

2

Modeling of solvent-dependent conformational transitions in Burkholderia cepacia lipase  

Microsoft Academic Search

BACKGROUND: The characteristic of most lipases is the interfacial activation at a lipid interface or in non-polar solvents. Interfacial activation is linked to a large conformational change of a lid, from a closed to an open conformation which makes the active site accessible for substrates. While for many lipases crystal structures of the closed and open conformation have been determined,

Peter Trodler; Rolf D Schmid; Jürgen Pleiss

2009-01-01

3

Solvent Dependent Studies of Conformational Relaxation in cis-1,3,5-Hexatriene with Transient Absorption Spectroscopy  

NASA Astrophysics Data System (ADS)

Two-color femtosecond transient absorption spectroscopy of 1,3-Cyclohexadiene (CHD) in condensed phase is used to study solvent dependent excited state dynamics. Ultraviolet excitation of CHD yields vibrationally hot cis-1,3,5-Hexatriene (Z-HT) through a ring opening reaction pathway from CHD. We characterize the barrier height of isomerization in ground state conformal relaxation of Z-HT following CHD ring opening as a function of solvent polarity, looking at both alkane and alcohol solvents.

Harris, Ahmasi; Sension, Roseanne

2004-03-01

4

An experimental study of the solvent-dependent self-assembly/disassembly and conformer preferences of gramicidin A.  

PubMed

The solvent dependence of self-assembly/disassembly kinetics and conformer preferences of the gramicidin A (GA) dimer is investigated using a combination of techniques, viz., electrospray ionization-ion mobility-mass spectrometry (IM-MS), collision-induced dissociation (CID), and hydrogen/deuterium exchange (HDX)-MS. IM-MS measurements reveal that there are possibly three distinct GA dimeric species, detected as sodium ion adduct ions [2GA + 2Na](2+), and these are assigned as the parallel ?-helix, antiparallel ?-helix, and head-to-head dimer. The monomerization kinetics and equilibrium abundances of the dimer ions depend upon solvent polarity. The antiparallel ?-helix was the thermodynamically preferred species in less polar solvents. HDX measurements and collision-induced dissociation (CID) of the intermediate complex confirm the well-protected dimer geometry with strong intermolecular hydrogen bonds. This combined IM-HDX-CID methodology provides a comprehensive view of GA self-assembly/disassembly in low dielectric solutions, showing its potential utility in solving solution-phase protein self-assembly/disassembly kinetics and providing structural information of the multimers at the same time. PMID:23855712

Chen, Liuxi; Chen, Shu-Hua; Russell, David H

2013-07-31

5

Solvent dependence of conformational stability and analysis of vibrational spectra of 2,2,3,3,3-pentafluoro-1-propanol.  

PubMed

The conformational stability of 2,2,3,3,3-pentafluoro-1-propanol was investigated by the DFT-B3LYP/6-311+G** and the ab initio MP2/6-311+G** calculations. The calculated potential energy curves of 2,2,3,3,3-pentafluoro-1-propanol at both levels of theory were consistent with three distinct minima that correspond to Trans-gauche-gauche (Tgg), trans-trans-gauche (Ttg) and trans-gauche-gauche(-) (Tgg1) conformers in the order of decreasing relative stability. The equilibrium constants for the conformational interconversion of 2,2,3,3,3-pentafluoro-1-propanol were calculated and found to correspond to an equilibrium mixture of about 46% Tgg, 43% Ttg and 11% Tgg1 conformations at 298.15K. The calculated (%Ttg/%Tgg) ratio of 0.93 is consistent with the 0.85 ratio of the observed intensities of the 772 and 794 cm(-1) lines in the Raman spectrum of the liquid. The nature of the high energy Ttg conformation was verified by solvent experiments using formamide (epsilon = 109.5) and acetonitrile (epsilon = 37). The vibrational frequencies of the molecule in its stable forms were computed at B3LYP level and complete vibrational assignments were made based on normal coordinate calculations and comparison with experimental data of the molecule. PMID:18280783

Badawi, Hassan M; Förner, Wolfgang

2008-01-05

6

Optimal Flexibility for Conformational Transitions in Macromolecules  

NASA Astrophysics Data System (ADS)

Conformational transitions in macromolecular complexes often involve the reorientation of leverlike structures. Using a simple theoretical model, we show that the rate of such transitions is drastically enhanced if the lever is bendable, e.g., at a localized hinge. Surprisingly, the transition is fastest with an intermediate flexibility of the hinge. In this intermediate regime, the transition rate is also least sensitive to the amount of “cargo” attached to the lever arm, which could be exploited by molecular motors. To explain this effect, we generalize the Kramers-Langer theory for multidimensional barrier crossing to configuration-dependent mobility matrices.

Neher, Richard A.; Möbius, Wolfram; Frey, Erwin; Gerland, Ulrich

2007-10-01

7

Transition path sampling of protein conformational changes  

NASA Astrophysics Data System (ADS)

Conformational changes in proteins often take place on long time scales compared to the molecular timescale. These long time scales, related to high free energy barriers, make such processes difficult to access with a straightforward molecular dynamics approach. The transition path sampling technique has been developed to overcome such timescale differences without assuming a predefined reaction coordinate. We review the transition path sampling methodology with the application of protein conformational change in mind. Using three case studies, based on previous work, we elucidate the strengths and pitfalls of the method. First, the extensive work on the folding of Trp-cage reveals how to sample parallel pathways, how to obtain rate constants, and how to extract reaction coordinates. The second case-study, on the folding of Trpzip4 ?-hairpin, illustrates how to treat long-lived intermediates in a conformational change. The final example showcases the light-triggered conformational transition of Photo-active Yellow Protein into its signaling state, highlighting the wealth of insight that can be gathered from a transition path sampling approach, including new hypotheses for reaction mechanisms. We end with an outlook discussing future developments and application of the methodology.

Juraszek, Jarek; Vreede, Jocelyne; Bolhuis, Peter G.

2012-03-01

8

Electroweak phase transition in nearly conformal technicolor  

SciTech Connect

We examine the temperature-dependent electroweak phase transition in extensions of the standard model in which the electroweak symmetry is spontaneously broken via strongly coupled, nearly conformal dynamics. In particular, we focus on the low energy effective theory used to describe minimal walking technicolor at the phase transition. Using the one-loop effective potential with ring improvement, we identify significant regions of parameter space which yield a sufficiently strong first-order transition for electroweak baryogenesis. The composite particle spectrum corresponding to these regions can be produced and studied at the Large Hadron Collider experiment. We note the possible emergence of a second phase transition at lower temperatures. This occurs when the underlying technicolor theory possesses a nontrivial center symmetry.

Cline, James M.; Jaervinen, Matti; Sannino, Francesco [McGill University, Montreal, Quebec H3A 2T8 (Canada); High Energy Center, University of Southern Denmark, Campusvej 55, DK-5230 Odense M (Denmark)

2008-10-01

9

Transitions to catalytically inactive conformations in EGFR kinase.  

PubMed

The epidermal growth factor receptor (EGFR) is a key protein in cellular signaling, and its kinase domain (EGFR kinase) is an intensely pursued target of small-molecule drugs. Although both catalytically active and inactive conformations of EGFR kinase have been resolved crystallographically, experimental characterization of the transitions between these conformations remains difficult. Using unbiased, all-atom molecular dynamics simulations, we observed EGFR kinase spontaneously transition from the active to the so-called "Src-like inactive" conformation by way of two sets of intermediate conformations: One corresponds to a previously identified locally disordered state and the other to previously undescribed "extended" conformations, marked by the opening of the ATP-binding site between the two lobes of the kinase domain. We also simulated the protonation-dependent transition of EGFR kinase to another ["Asp-Phe-Gly-out" ("DFG-out")] inactive conformation and observed similar intermediate conformations. A key element observed in the simulated transitions is local unfolding, or "cracking," which supports a prediction of energy landscape theory. We used hydrogen-deuterium (H/D) exchange measurements to corroborate our simulations and found that the simulated intermediate conformations correlate better with the H/D exchange data than existing active or inactive EGFR kinase crystal structures. The intermediate conformations revealed by our simulations of the transition process differ significantly from the existing crystal structures and may provide unique possibilities for structure-based drug discovery. PMID:23576739

Shan, Yibing; Arkhipov, Anton; Kim, Eric T; Pan, Albert C; Shaw, David E

2013-04-01

10

Transitions to catalytically inactive conformations in EGFR kinase  

PubMed Central

The epidermal growth factor receptor (EGFR) is a key protein in cellular signaling, and its kinase domain (EGFR kinase) is an intensely pursued target of small-molecule drugs. Although both catalytically active and inactive conformations of EGFR kinase have been resolved crystallographically, experimental characterization of the transitions between these conformations remains difficult. Using unbiased, all-atom molecular dynamics simulations, we observed EGFR kinase spontaneously transition from the active to the so-called “Src-like inactive” conformation by way of two sets of intermediate conformations: One corresponds to a previously identified locally disordered state and the other to previously undescribed “extended” conformations, marked by the opening of the ATP-binding site between the two lobes of the kinase domain. We also simulated the protonation-dependent transition of EGFR kinase to another [“Asp-Phe-Gly-out” (“DFG-out”)] inactive conformation and observed similar intermediate conformations. A key element observed in the simulated transitions is local unfolding, or “cracking,” which supports a prediction of energy landscape theory. We used hydrogen–deuterium (H/D) exchange measurements to corroborate our simulations and found that the simulated intermediate conformations correlate better with the H/D exchange data than existing active or inactive EGFR kinase crystal structures. The intermediate conformations revealed by our simulations of the transition process differ significantly from the existing crystal structures and may provide unique possibilities for structure-based drug discovery.

Shan, Yibing; Arkhipov, Anton; Kim, Eric T.; Pan, Albert C.; Shaw, David E.

2013-01-01

11

Analysis of protein conformational transitions using elastic network model.  

PubMed

In this chapter, we demonstrate the usage of a coarse-grained elastic network model to analyze protein conformational transitions in the NS3 helicase (NS3hel) of Hepatitis C virus (HCV). This analysis allows us to identify and visualize collective domain motions involved in the conformational transitions and predict the order of structural events during the transitions. It is highly efficient and applicable to many multi-domain protein structures which undergo large conformational changes to fulfill their functions. This method is made available through a Web server ( http://enm.lobos.nih.gov ). PMID:24061921

Zheng, Wenjun; Tekpinar, Mustafa

2014-01-01

12

Conformal microstrip patch circular array with orthogonal conformal stripline feed and all-angle transition  

Microsoft Academic Search

A prototype Ku-band, 32-element, circular microstrip patch array connected to a conformal stripline feed with an orthogonal all-angle transition was designed, fabricated and tested. The low cost antenna uses standard printed circuit technology. The antenna consists of a stripline feed conformally encased in a metal ring orthogonal to microstrip patch radiating elements which are etched on the front Duriod 5880

R. T. Cock; R. D. Cook

1997-01-01

13

Maximum Flux Transition Paths of Conformational Change.  

PubMed

Given two metastable states A and B of a biomolecular system, the problem is to calculate the likely paths of the transition from A to B. Such a calculation is more informative and more manageable if done for a reduced set of collective variables chosen so that paths cluster in collective variable space. The computational task becomes that of computing the "center" of such a cluster. A good way to define the center employs the concept of a committor, whose value at a point in collective variable space is the probability that a trajectory at that point will reach B before A. The committor "foliates" the transition region into a set of isocommittors. The maximum flux transition path is defined as a path that crosses each isocommittor at a point which (locally) has the highest crossing rate of distinct reactive trajectories. This path is based on the same principle as the minimum resistance path of Berkowitz et al (1983), but it has two advantages: (i) the path is invariant with respect to a change of coordinates in collective variable space and (ii) the differential equations that define the path are simpler. It is argued that such a path is nearer to an ideal path than others that have been proposed with the possible exception of the finite-temperature string method path. To make the calculation tractable, three approximations are introduced, yielding a path that is the solution of a nonsingular two-point boundary-value problem. For such a problem, one can construct a simple and robust algorithm. One such algorithm and its performance is discussed. PMID:20890401

Zhao, Ruijun; Shen, Juanfang; Skeel, Robert D

2010-08-10

14

Conformational Phase Transitions and ReEntrance Phenomena in Dendromesogens  

Microsoft Academic Search

We investigate theoretically the liquid crystalline phase behaviour of globular dendrimers consisting of a soft inner scaffold and peripheral mesogenic units attached to the scaffold by means of flexible chains. We use a generalised Onsager molecular theory to analyse model systems exhibiting conformational rod-sphere and rod-disc interconversions. Phase transitions normally not encountered in low molar mass mesogens are reported. For

A. F. Terzis; A. G. Vanakaras; D. J. Photinos

2000-01-01

15

Conformational transitions in semiflexible dendrimers induced by bond orientations  

NASA Astrophysics Data System (ADS)

We theoretically investigate the conformational properties of semiflexible dendrimers where the semiflexibility is implemented by topologically restricting the bond directions and orientations of the respective bond vectors. Molecular size (radius of gyration, Rg and Wiener index, W), shape factor ?, configurational free energy F, and the static structure factor, S(q) of semiflexible dendrimers are analyzed as a function of the bond orientation angle, ?. The size of the lower generation dendrimers decreases with increasing ? throughout the entire range of ?, ? ? (0, ?). The higher generation dendrimers show a non-uniform behavior, for compressed conformations the size decreases with increasing ?, while for the expanded ones it increases with the increase in ?. A conformational transition occurs for the higher generation dendrimers from the limiting value of the hard sphere to an ideal chain with the change in ?. This conformational transition at ? = ?/2 is also reflected in the configurational free energy. The configurational free energy exhibits a discontinuous behavior with the variation of ?, and this discontinuity occurs at ? = ?/2. However, no such conformational transition is observed with the variation of the bond direction angle, ?, generation, G and functionality, f of the semiflexible dendrimers. The flexible dendrimer, i.e., at ? = ?/2 is flanked between the compressed and expanded conformations of the semiflexible dendrimers resembling a hard sphere. The Kratky plot of the structure factor of all conformations quantitatively match with the results obtained from experiments and simulations in the low q-region in respect to the position of the major Kratky peak. For higher wave numbers, the Kratky plots for all conformations of semiflexible dendrimers agree with earlier theoretical results of model dendrimers [R. La Ferla, J. Chem. Phys. 106, 688 (1997); F. Ganazzoli, R. La Ferla, and G. Raffaini, Macromolecules 34, 4222 (2001)] but are in sharp contrast to the experimental [S. Rathgeber et al., J. Chem. Phys. 117, 4047 (2002); S. Rathgeber, T. Pakula, and V. Urban, J. Chem. Phys. 121, 3840 (2004)] and simulated [M. L. Mansfield and L. I. Klushin, Macromolecules 26, 4262 (1993)] scattering curves for the higher generation dendrimers. All compressed conformations (0 < ? < ?/2) behave as compact hard spheres, while the expanded conformations (?/2 < ? < ?) are relatively more open, partially decongesting the steric crowding among the monomers with increasing ?.

Kumar, Amit; Biswas, Parbati

2012-09-01

16

Ras Conformational Switching: Simulating Nucleotide-Dependent Conformational Transitions with Accelerated Molecular Dynamics  

PubMed Central

Ras mediates signaling pathways controlling cell proliferation and development by cycling between GTP- and GDP-bound active and inactive conformational states. Understanding the complete reaction path of this conformational change and its intermediary structures is critical to understanding Ras signaling. We characterize nucleotide-dependent conformational transition using multiple-barrier-crossing accelerated molecular dynamics (aMD) simulations. These transitions, achieved for the first time for wild-type Ras, are impossible to observe with classical molecular dynamics (cMD) simulations due to the large energetic barrier between end states. Mapping the reaction path onto a conformer plot describing the distribution of the crystallographic structures enabled identification of highly populated intermediate structures. These structures have unique switch orientations (residues 25–40 and 57–75) intermediate between GTP and GDP states, or distinct loop3 (46–49), loop7 (105–110), and ?5 C-terminus (159–166) conformations distal from the nucleotide-binding site. In addition, these barrier-crossing trajectories predict novel nucleotide-dependent correlated motions, including correlations of ?2 (residues 66–74) with ?3-loop7 (93–110), loop2 (26–37) with loop10 (145–151), and loop3 (46–49) with ?5 (152–167). The interconversion between newly identified Ras conformations revealed by this study advances our mechanistic understanding of Ras function. In addition, the pattern of correlated motions provides new evidence for a dynamic linkage between the nucleotide-binding site and the membrane interacting C-terminus critical for the signaling function of Ras. Furthermore, normal mode analysis indicates that the dominant collective motion that occurs during nucleotide-dependent conformational exchange, and captured in aMD (but absent in cMD) simulations, is a low-frequency motion intrinsic to the structure.

McCammon, J. Andrew

2009-01-01

17

Conformational Transitions and Convergence of Absolute Binding Free Energy Calculations  

PubMed Central

The Binding Energy Distribution Analysis Method (BEDAM) is employed to compute the standard binding free energies of a series of ligands to a FK506 binding protein (FKBP12) with implicit solvation. Binding free energy estimates are in reasonably good agreement with experimental affinities. The conformations of the complexes identified by the simulations are in good agreement with crystallographic data, which was not used to restrain ligand orientations. The BEDAM method is based on ? -hopping Hamiltonian parallel Replica Exchange (HREM) molecular dynamics conformational sampling, the OPLS-AA/AGBNP2 effective potential, and multi-state free energy estimators (MBAR). Achieving converged and accurate results depends on all of these elements of the calculation. Convergence of the binding free energy is tied to the level of convergence of binding energy distributions at critical intermediate states where bound and unbound states are at equilibrium, and where the rate of binding/unbinding conformational transitions is maximal. This finding mirrors similar observations in the context of order/disorder transitions as for example in protein folding. Insights concerning the physical mechanism of ligand binding and unbinding are obtained. Convergence for the largest FK506 ligand is achieved only after imposing strict conformational restraints, which however require accurate prior structural knowledge of the structure of the complex. The analytical AGBNP2 model is found to underestimate the magnitude of the hydrophobic driving force towards binding in these systems characterized by loosely packed protein-ligand binding interfaces. Rescoring of the binding energies using a numerical surface area model corrects this deficiency. This study illustrates the complex interplay between energy models, exploration of conformational space, and free energy estimators needed to obtain robust estimates from binding free energy calculations.

Lapelosa, Mauro; Gallicchio, Emilio; Levy, Ronald M.

2011-01-01

18

Energetics of conformational transition in proteolytically nicked myosin S-1  

SciTech Connect

Force production in muscle contraction results from structural changes in myosin crossbridges. During ATP hydrolysis myosin crossbridges exhibit at least two conformational states referred to as prepower stroke and postpower stroke respectively. Conformational changes in myosin proteolytic fragment S-1, which represent cross-bridges were studied in this research using UV absorption difference spectroscopy and /sup 19/F NMR. The heavy chain of S-1 is nicked, but left intact, by trypsin and several other proteases at different sites under controlled conditions. This was used to localize the site for non-denaturational reversible conformational change observed in S-1. Two specific tryptic S-1 fragments nicked at one and two sites have been used here, i.e., 27k-70k and 27k-50k-20k. Differential scanning calorimetric (DSC) studies of chymotryptic S-1 and trypsin treated S-1 indicate that the thermal stability of S-1 is unaffected by nicking. Nucleotide induced conformational changes were monitored with the UV difference absorption of tryptophan residues. The difference spectra induced by ATP differed from that induced by ADP. AMPPNP induced both forms of the spectra by varying temperature. When the 50k-20k junction was intact the non-denaturational structural transition between S1 states was retained.

Kamath, U.G.

1987-01-01

19

Conformational Transition Pathway in the Activation Process of Allosteric Glucokinase  

PubMed Central

Glucokinase (GK) is a glycolytic enzyme that plays an important role in regulating blood glucose level, thus acting as a potentially attractive target for drug discovery in the treatment of diabetes of the young type 2 and persistent hyperinsulinemic hypoglycemia of infancy. To characterize the activation mechanism of GK from the super-open state (inactive state) to the closed state (active state), a series of conventional molecular dynamics (MD) and targeted MD (TMD) simulations were performed on this enzyme. Conventional MD simulation showed a specific conformational ensemble of GK when the enzyme is inactive. Seven TMD simulations depicted a reliably conformational transition pathway of GK from the inactive state to the active state, and the components important to the conformational change of GK were identified by analyzing the detailed structures of the TMD trajectories. In combination with the inactivation process, our findings showed that the whole conformational pathway for the activation-inactivation-activation of GK is a one-direction circulation, and the active state is less stable than the inactive state in the circulation. Additionally, glucose was demonstrated to gradually modulate its binding pose with the help of residues in the large domain and connecting region of GK during the activation process. Furthermore, the obtained energy barriers were used to explain the preexisting equilibrium and the slow binding kinetic process of the substrate by GK. The simulated results are in accordance with the recent findings from the mutagenesis experiments and kinetic analyses. Our observations reveal a complicated conformational process in the allosteric protein, resulting in new knowledge about the delicate mechanisms for allosteric biological macromolecules that will be useful in drug design for targeting allosteric proteins.

Shi, Ting; Zhao, Yaxue; Chen, Yingyi; Li, Xiaobai; Liu, Xinyi; Huang, Zhimin; Zhang, Jian

2013-01-01

20

Constrained proper sampling of conformations of transition state ensemble of protein folding  

Microsoft Academic Search

Characterizing the conformations of protein in the transition state ensemble (TSE) is important for studying protein folding. A promising approach pioneered by Vendruscolo et al. [Nature (London) 409, 641 (2001)] to study TSE is to generate conformations that satisfy all constraints imposed by the experimentally measured phi values that provide information about the native likeness of the transition states. Faísca

Ming Lin; Jian Zhang; Hsiao-Mei Lu; Rong Chen; Jie Liang

2011-01-01

21

Sequence Recognition of DNA by Protein-Induced Conformational Transitions  

SciTech Connect

The binding of proteins to specific sequences of DNA is an important feature of virtually all DNA transactions. Proteins recognize specific DNA sequences using both direct readout (sensing types and positions of DNA functional groups) and indirect readout (sensing DNA conformation and deformability). Previously we showed that the P22 c2 repressor N-terminal domain (P22R NTD) forces the central non-contacted 5{prime}-ATAT-3{prime} sequence of the DNA operator into the B{prime} state, a state known to affect DNA hydration, rigidity and bending. Usually the B{prime} state, with a narrow minor groove and a spine of hydration, is reserved for A-tract DNA (TpA steps disrupt A-tracts). Here, we have co-crystallized P22R NTD with an operator containing a central 5{prime}-ACGT-3{prime} sequence in the non-contacted region. C {center_dot} G base pairs have not previously been observed in the B{prime} state and are thought to prevent it. However, P22R NTD induces a narrow minor groove and a spine of hydration to 5{prime}-ACGT-3{prime}. We observe that C {center_dot} G base pairs have distinctive destabilizing and disordering effects on the spine of hydration. It appears that the reduced stability of the spine results in a higher energy cost for the B to B{prime} transition. The differential effect of DNA sequence on the barrier to this transition allows the protein to sense the non-contacted DNA sequence.

Watkins, Derrick; Mohan, Srividya; Koudelka, Gerald B.; Williams, Loren Dean (GIT); (SUNYB)

2010-11-09

22

A small tripeptide AFA undergoes two state cooperative conformational transitions: implications for conformational biases in unfolded states.  

PubMed

It is important to understand the conformational biases that are present in unfolded states to understand protein folding. In this context, it is surprising that even a short tripeptide like AFA samples folded/ordered conformation as demonstrated recently by NMR experiments of the peptide in aqueous solution at 280 K. In this paper, we present molecular dynamics simulation of the peptide in explicit water using OPLS-AA/L all-atom force field. The results are in overall agreement with NMR results and provide some further insights. The peptide samples turn and extended conformational forms corresponding to minima in free energy landscape. Frequent transitions between the minima are observed due to modest free energy barriers. The turn conformation seems to be stabilized by hydrophobic interactions and possibly by bridging water molecules between backbone donors and acceptors. Thus the peptide does not sample conformations randomly, but samples well defined conformations. The peptide served as a model for folding-unfolding equilibrium in the context of peptide folding. Further, implications for drug design are also discussed. PMID:17627600

Patel, Sunita; Taimni, Richa; Sasidhar, Yellamraju U

2007-01-01

23

Studies of Conformational Transitions of Cytochrome C by the Spin-Label Method.  

National Technical Information Service (NTIS)

Isocyanide spin label (ISL) was used for studying the conformational transitions in cytochrome c. Molecular mobility of ISL, bound to the heme group of cytochrome c, is markedly increased when the monomeric form of cytochrome c is compounded into dimers. ...

L. M. Raykhman B. Annayev E. G. Rozantsev

1972-01-01

24

Energetics of conformational transition in proteolytically nicked myosin S-1  

Microsoft Academic Search

Force production in muscle contraction results from structural changes in myosin crossbridges. During ATP hydrolysis myosin crossbridges exhibit at least two conformational states referred to as prepower stroke and postpower stroke respectively. Conformational changes in myosin proteolytic fragment S-1, which represent cross-bridges were studied in this research using UV absorption difference spectroscopy and ¹⁹F NMR. The heavy chain of S-1

Kamath

1987-01-01

25

Solvent-dependent enantiodivergence in the chlorocyclization of unsaturated carbamates.  

PubMed

A remarkable solvent-controlled enantiodivergence is seen in the hydroquinidine 1,4-phthalazinediyl diether ((DHQD)2PHAL)-catalyzed chlorocyclization of unsaturated carbamates. Eyring plot analyses of this previously unreported reaction are used to probe and compare the R- and S-selective pathways. In the CHCl3/hexanes solvent system, the pro-R process shows a surprising increase in selectivity with increasing temperature. These studies point to a strongly solvent-dependent entropy-enthalpy balance between the pro-R and pro-S pathways. PMID:23671005

Garzan, Atefeh; Jaganathan, Arvind; Salehi Marzijarani, Nastaran; Yousefi, Roozbeh; Whitehead, Daniel C; Jackson, James E; Borhan, Babak

2013-05-13

26

Entropic mechanism of allosteric communication in conformational transitions of dihydrofolate reductase.  

PubMed

The mechanism of allosteric conformational transitions of Escherichia coli dihydrofolate reductase (DHFR) is investigated theoretically by applying a newly developed coarse-grained model. Functional forms of interaction potentials in the model depend on the local structural environments around those interactions to represent the many-residue effects due to atomic packing in each local region, and hence, this model is called "the chameleon model". The chameleon model consistently describes the free-energy landscape of two conformational transitions in the catalytic cycle of DHFR, which we call conformational transition 1 (CT1) and conformational transition 2 (CT2); CT1 is accompanied by the hydride transfer reaction, and CT2 is accompanied by the product ligand release. The transition state of CT1 is entropically stabilized by the disordering of loops at the peripheral regions of the protein, which enhances the positively correlated fluctuations at the center part of the protein, showing that the allosteric communication between distant regions through the central region is intrinsically associated with the entropic stabilization of the transition state. The transition state of CT2 is entropically stabilized through the mechanism that enhances the breathing motion of two domains, showing that the difference in the distribution of interactions brings about the difference in the transition mechanism between CT1 and CT2. The chameleon model opens a way to consistently describe the dynamical energy landscape of enzymatic reactions. PMID:23705773

Terada, Tomoki P; Kimura, Toru; Sasai, Masaki

2013-06-11

27

Influence of intermolecular interaction on kinetics of conformational transitions in poly-m-phenyleneisopthalamide  

SciTech Connect

The authors study the kinetics of conformational transitions during crystallization from a glasslike state and they compare the results obtained with the character of the conformational transitions in other polymers with a lower IMI energy. As the initial samples the authors used amorphous nonoriented PPIA films obtained from a polymer solution at a concentration of 1-20% in dimethylacetamide (DMA). The individual regions of the IR spectrum in which the difference between the amorphous and crystalline states of the polymer is most pronounced is shown. The authors found that IMI appreciably influences conformational transitions in polymers. Increase in IMI leads to an increase in /SUP E/ conf and, consequently, to a decrease in the kinetic flexibility of the molecule and an increase in the phase transition temperatures.

Pakhomov, P.M.; Korsvkov, V.E.; Novak, I.I.; Shablygin, M.V.

1986-02-01

28

Conformational transitions of weak polyacids grafted to nanoparticles  

NASA Astrophysics Data System (ADS)

The charge distribution on polyelectrolytes is a key factor, which controls their conformation and interactions. In weak polyelectrolytes, this distribution is determined by a number of factors, including the solvent conditions and local environment. In this work, we investigate charge distributions of chains end-grafted on a spherical nanoparticle in a salt solution, using grand canonical titration Monte Carlo simulations of a coarse-grained polymer model. In this approach, the ionization state of each polymer bead fluctuates based on the dissociation constant, pH of the solution, and interactions with other particles in the system. We determine charge and polymer conformations as functions of the pH and solvent quality. We compare the results to a fixed charge model and also investigate the role of grafting density and the effect of curvature on the film morphologies.

Barr, S. A.; Panagiotopoulos, A. Z.

2012-10-01

29

Conformational kinetics in liquid n-butane by transition path sampling  

NASA Astrophysics Data System (ADS)

A recent method for the study of transition states, transition path sampling, is applied to a classical problem of first order dynamics, the conformational transitions trans-gauche in pure liquid n-butane. Not only can the rate constant be calculated, but an ensemble of transition states can be extracted and analyzed as well. The results of the rate constant and the different distributions at the transition state are compared to those obtained from an equilibrium molecular dynamics simulation of the same system.

Ramírez, Jorge; Laso, Manuel

2001-10-01

30

?C Helix as a Switch in the Conformational Transition of Src/CDK-like Kinase Domains  

PubMed Central

One mechanism of regulating the catalytic activity of protein kinases is through conformational transitions. Despite great diversity in the structural changes involved in the transitions, a certain set of changes within the kinase domain (KD) has been observed for many kinases including Src and CDK2. We investigated this conformational transition computationally to identify the topological features that are energetically critical to the transition. Results from both molecular dynamics sampling and transition path optimization highlight the displacement of the ?C helix as the major energy barrier, mediating the switch of the KD between the active and down-regulated states. The critical role of the ?C helix is noteworthy by providing a rationale for a number of activation and deactivation mechanisms known to occur in cells. We find that kinases with the ?C helix displacement exist throughout the kinome, suggesting that this feature may have emerged early in evolution.

Huang, He; Zhao, Ruijun; Dickson, Bradley M.; Skeel, Robert D.; Post, Carol Beth

2013-01-01

31

Anomalous conformational transitions in cytochrome C adsorbing to Langmuir-Blodgett films  

NASA Astrophysics Data System (ADS)

Helix to beta conformational transitions in proteins has attracted much attention due to their relevance to fibril formation which is implicated in many neurological diseases. This study reports on unusual conformational transition of cytochrome C adsorbing to hydrophilic surface containing pure cationic lipid and mixed Langmuir-Blodgett films (LB films) of cationic and neutral lipids. Evidence for conformational changes of the protein from its native helical state to beta sheet comes from Circular dichroic spectroscopy (CD spectroscopy). Analysis of these samples using High resolution TEM (HRTEM) shows a typical fibrillar pattern with each strand spacing of about 0.41 nm across which can be attributed to the repeat distance of interdigitated neighboring hydrogen-bonded ribbons in a beta sheet. Changes in contact angles of protein adsorbing to the LB films together with the increased mass uptake of water using quartz crystal microbalance (QCM) confirm the role of positive charges in the conformational transition. Dehydration of the protein resulting from the excess water entrainment in the polar planes of the cationic lipid in hydrophilic surface seems to trigger the refolding of the protein to beta sheet while it retains its native conformation in hydrophobic films. The results suggest that drastic conformational changes in CytC adsorbing to cationic lipids may be of significance in its role as a peripheral membrane protein.

Sankaranarayanan, Kamatchi; Nair, B. U.; Dhathathreyan, A.

2013-05-01

32

Search for cyclopropylbenzene conformers by studying the S1 ? S0 electronic transition  

NASA Astrophysics Data System (ADS)

The resonance-enhanced multiphoton ionization, (1+1) REMPI and (2+2) REMPI S1 ? S0 spectra of cyclopropylbenzene (CPBz) have been measured in supersonic jet expansion under various cooling conditions. Both spectra include the pure electronic transition and one vibrationally induced transition. The vibronic analysis of these spectra revealed the presence of only one conformer. The present experiment cannot give the form of the conformer. The bisected structure, which was found by microwave spectroscopy [Q. Shen, C. Wells, M. Traetteberg, R.K. Bohn, A. Willis, J. Knee, J. Org. Chem., 66 (2001) 5840] is acceptable.

Philis, John G.; Wategaonkar, Sanjay

2007-05-01

33

Constrained proper sampling of conformations of transition state ensemble of protein folding  

NASA Astrophysics Data System (ADS)

Characterizing the conformations of protein in the transition state ensemble (TSE) is important for studying protein folding. A promising approach pioneered by Vendruscolo et al. [Nature (London) 409, 641 (2001)] to study TSE is to generate conformations that satisfy all constraints imposed by the experimentally measured ? values that provide information about the native likeness of the transition states. Faísca et al. [J. Chem. Phys. 129, 095108 (2008)] generated conformations of TSE based on the criterion that, starting from a TS conformation, the probabilities of folding and unfolding are about equal through Markov Chain Monte Carlo (MCMC) simulations. In this study, we use the technique of constrained sequential Monte Carlo method [Lin et al., J. Chem. Phys. 129, 094101 (2008); Zhang et al. Proteins 66, 61 (2007)] to generate TSE conformations of acylphosphatase of 98 residues that satisfy the ?-value constraints, as well as the criterion that each conformation has a folding probability of 0.5 by Monte Carlo simulations. We adopt a two stage process and first generate 5000 contact maps satisfying the ?-value constraints. Each contact map is then used to generate 1000 properly weighted conformations. After clustering similar conformations, we obtain a set of properly weighted samples of 4185 candidate clusters. Representative conformation of each of these cluster is then selected and 50 runs of Markov chain Monte Carlo (MCMC) simulation are carried using a regrowth move set. We then select a subset of 1501 conformations that have equal probabilities to fold and to unfold as the set of TSE. These 1501 samples characterize well the distribution of transition state ensemble conformations of acylphosphatase. Compared with previous studies, our approach can access much wider conformational space and can objectively generate conformations that satisfy the ?-value constraints and the criterion of 0.5 folding probability without bias. In contrast to previous studies, our results show that transition state conformations are very diverse and are far from nativelike when measured in cartesian root-mean-square deviation (cRMSD): the average cRMSD between TSE conformations and the native structure is 9.4 A? for this short protein, instead of 6 A? reported in previous studies. In addition, we found that the average fraction of native contacts in the TSE is 0.37, with enrichment in native-like ?-sheets and a shortage of long range contacts, suggesting such contacts form at a later stage of folding. We further calculate the first passage time of folding of TSE conformations through calculation of physical time associated with the regrowth moves in MCMC simulation through mapping such moves to a Markovian state model, whose transition time was obtained by Langevin dynamics simulations. Our results indicate that despite the large structural diversity of the TSE, they are characterized by similar folding time. Our approach is general and can be used to study TSE in other macromolecules.

Lin, Ming; Zhang, Jian; Lu, Hsiao-Mei; Chen, Rong; Liang, Jie

2011-02-01

34

Conformational statistics of random polyelectrolyte chain in theta region and transition to collapse: Qualitative study  

SciTech Connect

We study conformational properties of the polyelectrolyte chain with prescribed Bernoullian distribution of positive and negative charges on its backbone. For the case when the total charge of the chain is almost zero, the charge fluctuations are of special importance leading to the collapse transition qualitatively different from that expected for the uncharged homopolymers. The present case of collapse transition directly demonstrates the biological significance of nonuniformly charged polymers.

Qian, C.; Kholodenko, A.L.

1988-10-15

35

Structural plasticity and conformational transitions of HIV envelope glycoprotein gp120.  

PubMed

HIV envelope glycoproteins undergo large-scale conformational changes as they interact with cellular receptors to cause the fusion of viral and cellular membranes that permits viral entry to infect targeted cells. Conformational dynamics in HIV gp120 are also important in masking conserved receptor epitopes from being detected for effective neutralization by the human immune system. Crystal structures of HIV gp120 and its complexes with receptors and antibody fragments provide high-resolution pictures of selected conformational states accessible to gp120. Here we describe systematic computational analyses of HIV gp120 plasticity in such complexes with CD4 binding fragments, CD4 mimetic proteins, and various antibody fragments. We used three computational approaches: an isotropic elastic network analysis of conformational plasticity, a full atomic normal mode analysis, and simulation of conformational transitions with our coarse-grained virtual atom molecular mechanics (VAMM) potential function. We observe collective sub-domain motions about hinge points that coordinate those motions, correlated local fluctuations at the interfacial cavity formed when gp120 binds to CD4, and concerted changes in structural elements that form at the CD4 interface during large-scale conformational transitions to the CD4-bound state from the deformed states of gp120 in certain antibody complexes. PMID:23300605

Korkut, Anil; Hendrickson, Wayne A

2012-12-27

36

Conformational transition of polybenzimidazole in N,N-Dimethylacetamide/lithium chloride.  

NASA Astrophysics Data System (ADS)

Static light scattering and circular dichroism techniques have been used for the first time to study the chain conformation of a previously synthesized m-PBI sample in DMAc/LiCl. The chain conformation was studied as a function of a) polymer concentration (0.1 to 20 mg/mL) at a fixed salt concentration of 4 % LiCl and b) salt concentration (0.05 to 7 %) at a fixed polymer concentration of 0.3 mg/mL. As polymer or salt concentration was increased, the chains collapsed initially, and then underwent fluctuations in size without a significant decrease in their average size. The collapse was associated with a conformational transition from random coil to an ``extended wormlike'' chain. At polymer concentrations greater than 9 mg/mL, the average size of the polymer chain is relatively constant at 31.2 ± 1.7 nm. Circular dichroism measurements confirmed the conformational transitions that had been observed by indicating optical activity at polymer concentrations above 2 mg/mL. These results contribute to our overall understanding of chain stiffness and conformational transitions in PBI polymers, which may play an important role in the preparation of polymer electrolyte membranes via sol-gel processing.

Shogbon, Christopher; Zhang, Haifeng; Benicewicz, Brian; Akpalu, Yvonne; Brousseau, Jean-Luc

2006-03-01

37

Transition Networks for the Comprehensive Characterization of Complex Conformational Change in proteins  

SciTech Connect

Functionally relevant transitions between native conformations of a protein can be complex, involving, for example, the reorganization of parts of the backbone fold, and may occur via a multitude of pathways. Such transitions can be characterized by a transition network (TN), in which the experimentally determined end state structures are connected by a dense network of subtransitions via low-energy intermediates. We show here how the computation of a TN can be achieved for a complex protein transition. First, an efficient hierarchical procedure is used to uniformly sample the conformational subspace relevant to the transition. Then, the best path which connects the end states is determined as well as the rate-limiting ridge on the energy surface which separates them. Graph-theoretical algorithms permit this to be achieved by computing the barriers of only a small number out of the many subtransitions in the TN. These barriers are computed using the Conjugate Peak Refinement method. The approach is illustrated on the conformational switch of Ras p21. The best and the 12 next-best transition pathways, having rate-limiting barriers within a range of 10 kcal/mol, were identified. Two main energy ridges, which respectively involve rearrangements of the switch I and switch II loops, show that switch I must rearrange by threading Tyr32 underneath the protein backbone before the rate-limiting switch II rearrangement can occur, while the details of the switch II rearrangement differ significantly among the low-energy pathways.

Noe, F [University of Heidelberg; Krachtus, D [University of Heidelberg; Smith, Jeremy C [ORNL; Fischer, S. [University of Heidelberg

2006-03-01

38

Instantaneous Normal Modes as an Unforced Reaction Coordinate for Protein Conformational Transitions  

PubMed Central

Abstract We present a novel sampling approach to explore large protein conformational transitions by determining unique substates from instantaneous normal modes calculated from an elastic network model, and applied to a progression of atomistic molecular dynamics snapshots. This unbiased sampling scheme allows us to direct the path sampling between the conformational end states over simulation timescales that are greatly reduced relative to the known experimental timescales. We use adenylate kinase as a test system to show that instantaneous normal modes can be used to identify substates that drive the structural fluctuations of adenylate kinase from its closed to open conformations, in which we observe 16 complete transitions in 4 ?s of simulation time, reducing the timescale over conventional simulation timescales by two orders of magnitude. Analysis shows that the unbiased determination of substates is consistent with known pathways determined experimentally.

Peng, Cheng; Zhang, Liqing; Head-Gordon, Teresa

2010-01-01

39

Parallel cascade selection molecular dynamics (PaCS-MD) to generate conformational transition pathway  

NASA Astrophysics Data System (ADS)

Parallel Cascade Selection Molecular Dynamics (PaCS-MD) is proposed as a molecular simulation method to generate conformational transition pathway under the condition that a set of ``reactant'' and ``product'' structures is known a priori. In PaCS-MD, the cycle of short multiple independent molecular dynamics simulations and selection of the structures close to the product structure for the next cycle are repeated until the simulated structures move sufficiently close to the product. Folding of 10-residue mini-protein chignolin from the extended to native structures and open-close conformational transition of T4 lysozyme were investigated by PaCS-MD. In both cases, tens of cycles of 100-ps MD were sufficient to reach the product structures, indicating the efficient generation of conformational transition pathway in PaCS-MD with a series of conventional MD without additional external biases. Using the snapshots along the pathway as the initial coordinates, free energy landscapes were calculated by the combination with multiple independent umbrella samplings to statistically elucidate the conformational transition pathways.

Harada, Ryuhei; Kitao, Akio

2013-07-01

40

The Preliminary Stretching Effect on Mechanical Properties of Natural and Synthetic Polyamide fibres and Conformational Transitions  

NASA Astrophysics Data System (ADS)

The preliminary stretching effect on mechanical properties of natural (wool, hair, and silk) and synthetic polyamide fibres (nylon, capron) and conformational transitions are investigated by using a tensile tester. It is shown that ?-keratin fibres (wool and hair) show silk-like properties and properties of synthetic polyamide fibres for preliminary extension of 18-24% and 34-38%, respectively.

Aksakal, Baki; Phoshkina, Svetlana P.; Darvish, Diana M.; Tsobkallo, Ekaterina S.; Alekberov, Vilayet

2007-04-01

41

Controlling chemical self-assembly by solvent-dependent dynamics.  

PubMed

The influence of the ratio between poor and good solvent on the stability and dynamics of supramolecular polymers is studied via a combination of experiments and simulations. Step-wise addition of good solvent to supramolecular polymers assembled via a cooperative (nucleated) growth mechanism results in complete disassembly at a critical good/poor solvent ratio. In contrast, gradual disassembly profiles upon addition of good solvent are observed for isodesmic (non-nucleated) systems. Due to the weak association of good solvent molecules to monomers, the solvent-dependent aggregate stability can be described by a linear free-energy relationship. With respect to dynamics, the depolymerization of ?-conjugated oligo(p-phenylene vinylene) (OPV) assemblies in methylcyclohexane (MCH) upon addition of chloroform as a good solvent is shown to proceed with a minimum rate around a critical chloroform/MCH solvent ratio. This minimum disassembly rate bears an intriguing resemblance to phenomena observed in protein unfolding, where minimum rates are observed at the thermodynamic midpoint of a protein denaturation experiment. A kinetic nucleation-elongation model in which the rate constants explicitly depend on the good solvent fraction is developed to rationalize the kinetic traces and further extend the insights by simulation. It is shown that cooperativity, i.e., the nucleation of new aggregates, plays a key role in the minimum polymerization and depolymerization rate at the critical solvent composition. Importantly, this shows that the mixing protocol by which one-dimensional aggregates are prepared via solution-based processing using good/poor solvent mixtures is of major influence on self-assembly dynamics. PMID:22808949

Korevaar, Peter A; Schaefer, Charley; de Greef, Tom F A; Meijer, E W

2012-08-02

42

Simulation of conformational transitions by the restricted perturbation-targeted molecular dynamics method  

NASA Astrophysics Data System (ADS)

A method for the simulation of conformational transitions is presented. The method, based on targeted molecular dynamics (TMD), limits the conformational change at each molecular dynamics step to a fixed size, that minimizes the root mean square deviation from the target. The method is more efficient than standard TMD and yields lower energy pathways, but, like the TMD method, requires only a single molecular dynamics simulation. Test calculations and comparisons with standard TMD calculations for the alanine dipeptide with the analytic continuum electrostatics implicit solvent model are presented.

van der Vaart, Arjan; Karplus, Martin

2005-03-01

43

Conformationally induced vibronic transitions in S0<--S1 spectra of n-propylbenzene  

NASA Astrophysics Data System (ADS)

Dispersed fluorescence spectra (S0<--S1) of two conformational isomers of n-propylbenzene have been measured in a supersonic free jet expansion. The results show that the vibronic features in emission from the S1 zero-point levels in two conformers are significantly different, and most notably, the transitions due to ring-chain torsional mode are active only in the spectra of the gauche conformer. Relative stability of the conformers in the ground state has been reinvestigated by the ab initio quantum chemistry method at the MP2/6-311++G(d,p) and MP2/ccpVTZ levels of theory. In contrast to earlier reports, the present theoretical studies predict that the gauche conformer is ~2.5 kJ/mol more stable [MP2/6-311++G(d,p)] than the trans. The effects of propyl substitution on phenyl ring vibrational modes have been analyzed by comparing the calculated (ab initio, DFT/B3LYP/6-31G**) displacements of ring atoms for different normal modes with those of the vibrational modes of unsubstituted benzene. The implications of spectral dissimilarity of the conformers on their excited state lifetimes [Borst et al., J. Chem. Phys. 116, 7057 (2002)] have been discussed.

Panja, Sujit S.; Chakraborty, Tapas

2003-11-01

44

The energy profiles of atomic conformational transition intermediates of adenylate kinase  

PubMed Central

The elastic network interpolation (ENI)1 is a computationally efficient and physically realistic method to generate conformational transition intermediates between two forms of a given protein. However it can be asked whether these calculated conformations provide good representatives for these intermediates. In this study, we use ENI to generate conformational transition intermediates between the open form and the closed forms of adenylate kinase (AK). Based on C?-only intermediates, we construct atomic intermediates by grafting all the atoms of known AK structures onto the C? atoms and then perform CHARMM energy minimization to remove steric conflicts and optimize these intermediate structures. We compare the energy profiles for all intermediates from both the CHARMM force-field and from knowledge-based energy functions. We find that the CHARMM energies can successfully capture the two energy minima representing the open AK and closed AK forms, while the energies computed from the knowledge-based energy functions can detect the local energy minimum representing the closed AK form and show some general features of the transition pathway with a somewhat similar energy profile as the CHARMM energies. The combinatorial extension (CE) structural alignment2 and the k-means clustering algorithm are then used to show that known PDB structures closely resemble computed intermediates along the transition pathway.

Feng, Yaping; Yang, Lei; Kloczkowski, Andrzej; Jernigan, Robert L.

2009-01-01

45

Transitions between Elongated Conformations of Ubiquitin [M+11H]11+ Enhance Hydrogen/Deuterium Exchange  

PubMed Central

Hydrogen/deuterium (H/D) exchange reactions between different elongated conformations of [M+11H]11+ ions of ubiquitin and D2O are studied by a combination of ion mobility spectrometry (IMS) and mass spectrometry techniques. Three conformers (B, C, and D), resolved in the IMS separation, each exchange ~27 hydrogens upon exposure to 0.06 torr of D2O vapor for ~35 to 40 ms. However, a region of the IMS spectrum that appears between the C and D states (corresponding to ions that undergo a structural transition during the mobility separation) undergoes substantially more exchanges (~39 total sites, 44% more than the B, C, and D states). Selection and activation of the individual B, C, and D states reveals that the increased H/D exchange occurs during the transition between structures. Overall, these studies suggest a key process in establishing the maximum exchange levels involves structural transitions, which allow protected sites to be exposed for some fraction of the reaction time. Analysis of changes in exchange levels upon structural transitions can provide insight about common regions of structure that exist in the B, C, and D conformations.

Bohrer, Brian C.; Atlasevich, Natalya; Clemmer, David E.

2011-01-01

46

Conformational Transition Pathways in Signaling and Enzyme Catalysis Explored by Computational Methods  

NASA Astrophysics Data System (ADS)

Biomolecules are dynamic in nature and visit a number of states while performing their biological function. However, understanding how they interconvert between functional substates is a challenging task. In this thesis, we employ enhanced computational strategies to reveal in atomistic resolution transition states and molecular mechanism along conformational pathways of the signaling protein Nitrogen Regulatory Protein C (NtrC) and the enzyme Adenylate Kinase (Adk). Targeted Molecular Dynamics (TMD) simulations and NMR experiments have previously found the active/inactive interconversion of NtrC is stabilized by non-native transient contacts. To find where along the conformational pathway they lie and probe the existence of multiple intermediates, a beyond 8mus-extensive mapping of the conformational landscape was performed by a multitude of straightforward MD simulations relaxed from the biased TMD pathway. A number of metastable states stabilized by local interactions was found to underline the conformational pathway of NtrC. Two spontaneous transitions of the last stage of the active-to-inactive conversion were identified and used in path sampling procedures to generate an ensemble of truly dynamic reactive pathways. The transition state ensemble (TSE) and mechanistic descriptors of this transition were revealed in atomic detail and verified by committor analysis. By analyzing how pressure affects the dynamics and function of two homologous Adk proteins - the P.Profundum Adk surviving at 700atm pressure in the deep sea, and the E. coli Adk that lives at ambient pressures - we indirectly obtained atomic information about the TSE of the large-amplitude rate-limiting conformational opening of the Adk lids. Guided by NMR experiments showing significantly decreased activation volumes of the piezophile compared to its mesophilic counterpart, TMD simulations revealed the formation of an extended hydrogen-bonded water network in the transition state of the piezophile that can explain the experimentally measured activation volume differences. The transition state of the conformational change was proposed to lie close to the closed state. Additionally, a number of descriptors were used to characterize the free energy landscape of the mesophile. It was found that the features of landscape are highly sensitive to the binding of different ligands, their protonation states and the presence of magnesium.

Pachov, Dimitar V.

47

The Conformational Transition Pathways of ATP-Binding Cassette Transporter BtuCD Revealed by Targeted Molecular Dynamics Simulation  

PubMed Central

BtuCD is a member of the ATP-binding cassette transporters in Escherichia coli that imports vitamin B12 into the cell by utilizing the energy of ATP hydrolysis. Crystal structures of BtuCD and its homologous protein HI1470/1 in various conformational states support the “alternating access” mechanism which proposes the conformational transitions of the substrate translocation pathway at transmembrane domain (TMD) between the outward-facing and inward-facing states. The conformational transition at TMD is assumed to couple with the movement of the cytoplasmic nucleotide-binding domains (NBDs) driven by ATP hydrolysis/binding. In this study, we performed targeted molecular dynamics (MD) simulations to explore the atomic details of the conformational transitions of BtuCD importer. The outward-facing to inward-facing (O?I) transition was found to be initiated by the conformational movement of NBDs. The subsequent reorientation of the substrate translocation pathway at TMD began with the closing of the periplasmic gate, followed by the opening of the cytoplamic gate in the last stage of the conformational transition due to the extensive hydrophobic interactions at this region, consistent with the functional requirement of unidirectional transport of the substrates. The reverse inward-facing to outward-facing (I?O) transition was found to exhibit intrinsic diversity of the conformational transition pathways and significant structural asymmetry, suggesting that the asymmetric crystal structure of BtuCD-F is an intermediate state in this process.

Weng, Jingwei; Fan, Kangnian; Wang, Wenning

2012-01-01

48

The kinetics of effector binding to phosphofructokinase. The influence of effectors on the allosteric conformational transition.  

PubMed

1. The extent of the allosteric transition from the R into the T conformation of rabbit skeletal muscle phosphofructokinase induced by Mg2+-1,N6-etheno-ATP was determined by stopped-flow fluorimetry from the amplitude of the slow phase of the Mg2+-1,N6-etheno-ATP fluorescence enhancement [Roberts & Kellet (1979) Biochem. J. 183, 349--360]. 2. The amplitude of the slow phase was decreased by low concentrations of the activators cyclic AMP and fructose 1,6-bisphosphate, but increased in a complex manner by the inhibitor citrate. 3. Mg2+-1,N6-etheno-ATP and Mg2+-ATP are unable to induce the T conformation to a detectable extent in the presence of saturating cyclic AMP, but can do so readily in the presence of saturating fructose 1,6-bisphosphate. 4. The conformational transitions induced in enzyme alone by different ligands were observed by changes in intrinsic protein fluorescence. In general, an R-type conformation has diminished protein fluorescence compared with a T-type conformation. 5. Mg2+-ATP exerts a complex effect on protein fluorescence; both the enhancement at low concentrations and the quenching at high concentrations of Mg2+-ATP result from the binding of Mg2+-ATP to the inhibitory site and the ensuing allosteric transition. Enhancement reflects the extent of the allosteric transition and involves both tyrosine and tryptophan, probably in the region of the active site; quenching reflects occupation of the inhibitory site and involves tyrosine at the inhibitory site. 6. The mechanism of the allosteric transition from the R into the T conformation induced by Mg2+-1,N6-etheno-ATP at low concentrations occurs predominantly by a 'prior-isomerization' pathway; at higher concentrations a limited contribution from a 'substrate-guided' pathway occurs. 7. The allosteric behaviour of phosphofructokinase with respect to Mg2+-ATP and Mg2+-1,N6-ethenol-ATP binding may be accounted for in terms of the simple, concerted model. PMID:6260084

Roberts, D; Kellett, G L

1980-09-01

49

pH-dependent conformational change of gastric mucin leads to sol-gel transition.  

PubMed Central

We present dynamic light scattering (DLS) and hydrophobic dye-binding data in an effort to elucidate a molecular mechanism for the ability of gastric mucin to form a gel at low pH, which is crucial to the barrier function of gastric mucus. DLS measurements of dilute mucin solutions were not indicative of intermolecular association, yet there was a steady fall in the measured diffusion coefficient with decreasing pH, suggesting an apparent increase in size. Taken together with the observed rise in depolarized scattering ratio with decreasing pH, these results suggest that gastric mucin undergoes a conformational change from a random coil at pH >/= 4 to an anisotropic, extended conformation at pH < 4. The increased binding of mucin to hydrophobic fluorescent with decreasing pH indicates that the change to an extended conformation is accompanied by exposure of hydrophobic binding sites. In concentrated mucin solutions, the structure factor S(q, t) derived from DLS measurements changed from a stretched exponential decay at pH 7 to a power-law decay at pH 2, which is characteristic of a sol-gel transition. We propose that the conformational change facilitates cross-links among mucin macromolecules through hydrophobic interactions at low pH, which in turn leads to a sol-gel transition when the mucin solution is sufficiently concentrated.

Cao, X; Bansil, R; Bhaskar, K R; Turner, B S; LaMont, J T; Niu, N; Afdhal, N H

1999-01-01

50

Luminescence and Absorption Spectra of Polyatomic Molecules Subjected to Conformational Transitions  

NASA Astrophysics Data System (ADS)

A general approach and results of specific calculations of conjugated vibronic absorption and fluorescence spectra of “soft” molecules subjected to conformational transitions are presented. The vibronic spectra of these molecules exhibit significant anomalies such as a large energy gap between the fluorescence and absorption spectra, a strong deviation from the mirror symmetry, etc., which cannot be explained within the framework of the theory of vibronic spectra based on single-well adiabatic potentials.

Naumov, A. V.; Naumova, N. L.; Osad'Ko, I. S.

2001-11-01

51

Pyranose ring transition state is derived from cellobiohydrolase I induced conformational stability and glycosidic bond polarization.  

PubMed

Understanding carbohydrate ring pucker is critical to rational design in materials and pharmaceuticals. Recently we have generalized our adaptive reaction coordinate force biasing method to perform calculations on multidimensional reaction coordinates. We termed this the Free Energies from Adaptive Reaction Coordinate Forces (FEARCF) method. Using FEARCF in SCC-DFTB QM/MM non-Boltzmann simulations, we are able to calculate multidimensional ring pucker free energies of conformation. Here we apply this to the six-membered glucopyranose ring located in an eight-membered ? 1-4 linked octaose oligosaccharide (cellooctaose). The cellooctaose was built following the conformation of the saccharides bound to cellobiohydrolase I (CBHI) of Trichoderma reesei as reported in the 7CEL crystal structure obtained from the PDB. We calculate the free energy of ring puckering of the glucopyranose ring at the -1 position in vacuum, in water, and bound to the protein. We find that the protein induces (4)E and (4)H(3) conformations that are much more stable than the usually preferred (4)C(1) conformer. Furthermore, for the (4)H(3) conformation in the catalytic binding domain, there is significant electronic rearrangement that drives the structure toward the transition state of the glycosylation reaction. PMID:20795726

Barnett, Christopher B; Wilkinson, Karl A; Naidoo, Kevin J

2010-09-22

52

Theoretical models of conformational transitions and ion conduction in voltage-dependent ion channels: Bioferroelectricity and superionic conduction  

Microsoft Academic Search

Theoretical studies of the structure and function of ion channels are reviewed, with emphasis on the underlying physical phenomena. Nerve and muscle membranes exhibit behavior interpretable as ferroelectric: Studies show that conformational transitions in voltage-dependent ion channels can be understood in terms of transitions from a ferroelectric state to a superionically conducting state. The ferroelectric-superionic transition hypothesis is supported by

H. Richard Leuchtag; Vladimir S. Bystrov

1999-01-01

53

Solvent-dependent conformation of amylose tris(phenylcarbamate) as deduced from scattering and viscosity data.  

PubMed

The z-average mean-square radius of gyration S(2)(z), the particle scattering function P(k), the second virial coefficient, and the intrinsic viscosity [eta] have been determined for amylose tris(phenylcarbamate) (ATPC) in methyl acetate (MEA) at 25 degrees C, in ethyl acetate (EA) at 33 degrees C, and in 4-methyl-2-pentanone (MIBK) at 25 degrees C by light and small-angle X-ray scattering and viscometry as functions of the weight-average molecular weight in a range from 2 x 10(4) to 3 x 10(6). The first two solvents attain the theta state, whereas the last one is a good solvent for the amylose derivative. Analysis of the S(2)(z), P(k), and [eta] data based on the wormlike chain yields h (the contour length or helix pitch per repeating unit) = 0.37 +/- 0.02 and lambda(-1) (the Kuhn segment length) = 15 +/- 2 nm in MEA, h = 0.39 +/- 0.02 and lambda(-1) = 17 +/- 2 nm in EA, and h = 0.42 +/- 0.02 nm and lambda(-1) = 24 +/- 2 nm in MIBK. These h values, comparable with the helix pitches (0.37-0.40 nm) per residue of amylose triesters in the crystalline state, are somewhat larger than the previously determined h of 0.33 +/- 0.02 nm for ATPC in 1,4-dioxane and 2-ethoxyethanol, in which intramolecular hydrogen bonds are formed between the C==O and NH groups of the neighbor repeating units. The slightly extended helices of ATPC in the ketone and ester solvents are most likely due to the replacement of those hydrogen bonds by intermolecular hydrogen bonds between the NH groups of the polymer and the carbonyl groups of the solvent. PMID:19402142

Fujii, Taichi; Terao, Ken; Tsuda, Maiko; Kitamura, Shinichi; Norisuye, Takashi

2009-09-01

54

Many local motions cooperate to produce the adenylate kinase conformational transition  

PubMed Central

Conformational transitions are functionally important in many proteins. In the enzyme adenylate kinase (AK), two small domains (LID and NMP) close over the larger CORE domain; the reverse (opening) motion limits the rate of catalytic turnover. Here, using double-well G? simulations of E. coli AK, we elaborate on previous investigations of the AK transition mechanism by characterizing the contributions of rigid-body (Cartesian), backbone dihedral, and contact motions to the transition state (TS) properties. In addition, we compare an apo simulation to a pseudo-ligand-bound simulation to reveal insight into allostery. In Cartesian space, LID closure precedes NMP closure in the bound simulation, consistent with prior coarse-grained models of the AK transition. However, NMP-first closure is preferred in the apo simulation. In backbone dihedral space, we find that as expected, backbone fluctuations are reduced in the O to C transition in parts of all three domains. Among these “quenching” residues, most in the CORE, especially residues 11-13, are rigidified in the TS of the bound simulation, while residues 42-44 in the NMP are flexible in the TS. In contact space, in both apo and bound simulations, one nucleus of closed state contacts includes parts of the NMP and CORE; CORE-LID contacts are absent in the TS of the apo simulation but formed in the TS of the bound simulation. From these results, we predict mutations that will perturb the opening and/or closing transition rates by changing the entropy of dihedrals and/or the enthalpy of contacts. Furthermore, regarding allostery, the fully closed structure is populated in the apo simulation, but our contact results imply that ligand binding shifts the preferred O/C transition pathway, thus precluding a simple conformational selection mechanism. Finally, the analytical approach and the insights derived from this work may inform the rational design of flexibility and allostery in proteins.

Daily, Michael D.; Phillips, George N.; Cui, Qiang

2010-01-01

55

The methanol-induced transition and the expanded helical conformation in hen lysozyme.  

PubMed Central

Methanol-induced conformational transitions of hen egg white lysozyme were investigated with a combined use of far- and near-UV CD and NMR spectroscopies, ANS binding and small-angle X-ray scattering. Addition of methanol induced no global change in the native conformation itself, but induced a transition from the native state to the denatured state which was highly cooperative, as shown by the coincidence of transition curves monitored by the far- and near-UV CD spectroscopy, by isodichroic points in the far- and near-UV CD spectra and by the concomitant disappearance of individual 1H NMR signals of the native state. The ANS binding experiments could detect no intermediate conformer similar to the molten globule state in the process of the methanol denaturation. However, at high concentration of methanol, e.g., 60% (v/v) methanol/water, a highly helical state (H) was realized. The H state had a helical content much higher than the native state, monitored by far-UV CD spectroscopy, and had no specific tertiary structure, monitored both by near-UV CD and NMR spectroscopy. The radius of gyration in the H state, 24.9 angstroms, was significantly larger than that in the native state (15.7 angstroms). The Kratky plot for the H state did not show a clear peak and was quite similar to that for the urea-denatured state, indicating a complete lack of globularity. Thus we conclude that the H state has a considerably expanded, flexible broken rod-like conformation which is clearly distinguishable from the "molten globule" state. The stability of both N and H states depends on pH and methanol concentration. Thus a phase diagram involving N and H was constructed.

Kamatari, Y. O.; Konno, T.; Kataoka, M.; Akasaka, K.

1998-01-01

56

How and why do transition dipole moment orientations depend on conformer structure?  

PubMed

A remarkable influence of the orientation of a polar side chain on the direction of the S(1) ? S(0) transition dipole moment of monosubstituted benzenes was previously reported from high-resolution electronic spectroscopy. In search for a more general understanding of this non-Condon behavior, we investigated ethylamino-substituted indole and benzene (tryptamine and 2-phenylethylamine) using ab initio theory and compared the results to rotationally resolved laser-induced fluorescence measurements. The interaction of the ethylamino side chain with the benzene chromophore can evoke a rotation and a change of ordering of the molecular orbitals involved in the excitation, leading to state mixing and large changes in the orientation of the excited-state transition dipole moment. These changes are much less pronounced in tryptamine with the indole chromophore, where a rotation of the transition dipole moment is attributed to Rydberg contributions of the nitrogen atom of the chromophore. For phenylethylamine, a strong dependence of the oscillator strengths of the lowest two singlet states from the conformation of the side chain is found, which makes the use of experimental vibronic intensities for assessment of relative conformer stabilities at least questionable. PMID:21500787

Brand, Christian; Meerts, W Leo; Schmitt, Michael

2011-04-18

57

Free energy of transition for the individual alkaline conformers of yeast iso-1-cytochrome c.  

PubMed

Direct protein electrochemistry was used to obtain the thermodynamic parameters of transition from the native (state III) to the alkaline (state IV) conformer for untrimethylated Saccharomyces cerevisiae iso-1-cytochrome c expressed in E. coli and its single and multiple lysine-depleted variants. In these variants, one or more of the lysine residues involved in axial Met substitution (Lys72, Lys73, and Lys79) was mutated to alanine. The aim of this work is to determine the thermodynamic affinity of each of the substituting lysines for the heme iron and evaluate the interplay of enthalpic and entropic factors. The equilibrium constants for the deprotonation reaction of Lys72, 73, and 79 were computed for the minimized MD average structures of the wild-type and mutated proteins, applying a modified Tanford-Kirkwood calculation. Solvent accessibility calculations for the substituting lysines in all variants were also performed. The transition enthalpy and entropy values within the protein series show a compensatory behavior, typical of a process involving extensive solvent reorganization effects. The experimental and theoretical data indicate that Lys72 most readily deprotonates and replaces M80 as the axial heme iron ligand, whereas Lys73 and Lys79 show comparably higher pKa values and larger transition free energies. A good correlation is found within the series between the lowest calculated Lys pKa value and the corresponding experimental pKa value, which can be interpreted as indicative of the deprotonating lysine itself acting as the triggering group for the conformational transition. The triple Lys to Ala mutant, in which no lysine residues are available for heme iron binding, features transition thermodynamics consistent with a hydroxide ion replacing the axial methionine ligand. PMID:17243773

Battistuzzi, Gianantonio; Borsari, Marco; De Rienzo, Francesca; Di Rocco, Giulia; Ranieri, Antonio; Sola, Marco

2007-01-23

58

Effect of water on the temperatures of human immunoglobulin conformation transitions  

NASA Astrophysics Data System (ADS)

A differential thermal analysis of native and denaturated human immunoglobulin (G isotype) and mixtures of the native protein with water over the temperature range of 80-570 K is conducted. Temperatures of the protein conformational transitions and the effect of water on them are investigated. The limit of water solubility in the native protein is determined calorimetrically from the enthalpy of excess water phase melting. A physical state diagram of the immunoglobulin-water system over a wide range of temperatures and component concentrations is built and analyzed.

Ur'yash, V. F.; Kokurina, N. Yu.

2013-10-01

59

Conformational transitions during FtsK translocase activation of individual XerCD-dif recombination complexes.  

PubMed

Three single-molecule techniques have been used simultaneously and in tandem to track the formation in vitro of single XerCD-dif recombination complexes. We observed the arrival of the FtsK translocase at individual preformed synaptic complexes and demonstrated the conformational change that occurs during their activation. We then followed the reaction intermediate transitions as Holliday junctions formed through catalysis by XerD, isomerized, and were converted by XerC to reaction products, which then dissociated. These observations, along with the calculated intermediate lifetimes, inform the reaction mechanism, which plays a key role in chromosome unlinking in most bacteria with circular chromosomes. PMID:24101525

Zawadzki, Pawel; May, Peter F J; Baker, Rachel A; Pinkney, Justin N M; Kapanidis, Achillefs N; Sherratt, David J; Arciszewska, Lidia K

2013-10-07

60

Conformational transition of polyelectrolyte chains extending over the de Gennes regime in slitlike nanochannels  

NASA Astrophysics Data System (ADS)

The confinement-induced conformational transitions of the polyelectrolyte chain are characterized with the coarse-grained Brownian dynamics simulations and the blob theory. Submicron-sized biopolymer xanthan is chosen as a model polyelectrolyte taking into account both flexible and semiflexible chains for comparison. Confined flexible and semiflexible chains exhibit a nonmonotonic variation in size in weak confinements, where the relative radius of gyration shows a dip and then increases when decreasing the channel width. The rigid chain, realized at low screening, exhibits a sigmoidal transition without minima in size. Major attention should be on the dependence of scaling law exponents on the screening effect of the solution in the moderate confinement of the de Gennes regime. Our findings are expected to provide useful information and new insight into the confined polyelectrolytes when relevant micro/nanochannels are designed and fabricated.

Chun, Myung-Suk

2012-09-01

61

Morphologies and conformation transition of lentinan in aqueous NaOH solution.  

PubMed

Molecular morphologies and conformation transition of lentinan, a beta-(1-->3)-D-glucan from Lentinus edodes, were studied in aqueous NaOH solution by atomic force microscopy (AFM), viscometry, multiangle laser light scattering, and optical rotation measurements. The results revealed that lentinan exists as triple-helical chains and as single random-coil chains at NaOH concentration lower than 0.05M and higher than 0.08M, respectively. Moreover, the dramatic changes in weight-average molecular weight Mw, radius of gyration [s2](1/2), intrinsic viscosity [eta], as well as specific optical rotation at 589 nm [alpha]589 occurred in a narrow range of NaOH concentration between 0.05 and 0.08M NaOH, indicating that the helix-coil conformation transition of lentinan was carried out more easily than that of native schizophyllan and scleroglucan, and was irreversible. For the first time, we confirmed that the denatured lentinan molecule, which was dissolved in 0.15M NaOH to be disrupted into single coil chains, could be renatured as triple helical chain by dialyzing against abundant water in the regenerated cellulose tube at ambient temperature (15 degrees C). In view of the AFM image, lentinan in aqueous solution exhibited the linear, circular, and branched species of triple helix compared with native linear schizophyllan or scleroglucan. PMID:15356872

Zhang, Xufeng; Zhang, Lina; Xu, Xiaojuan

2004-10-01

62

CEF1/CDC5 alleles modulate transitions between catalytic conformations of the spliceosome.  

PubMed

Conformational change within the spliceosome is required between the first and second catalytic steps of pre-mRNA splicing. A prior genetic screen for suppressors of an intron mutant that stalls between the two steps yielded both prp8 and non-prp8 alleles that suppressed second-step splicing defects. We have now identified the strongest non-prp8 suppressors as alleles of the NTC (Prp19 complex) component, CEF1. These cef1 alleles generally suppress second-step defects caused by a variety of intron mutations, mutations in U6 snRNA, or deletion of the second-step protein factor Prp17, and they can activate alternative 3' splice sites. Genetic and functional interactions between cef1 and prp8 alleles suggest that they modulate the same event(s) in the first-to-second-step transition, most likely by stabilization of the second-step spliceosome; in contrast, alleles of U6 snRNA that also alter this transition modulate a distinct event, most likely by stabilization of the first-step spliceosome. These results implicate a myb-like domain of Cef1/CDC5 in interactions that modulate conformational states of the spliceosome and suggest that alteration of these events affects splice site use, resulting in alternative splicing-like patterns in yeast. PMID:22408182

Query, Charles C; Konarska, Maria M

2012-03-08

63

Identifying allosteric fluctuation transitions between different protein conformational states as applied to Cyclin Dependent Kinase 2  

PubMed Central

Background The mechanisms underlying protein function and associated conformational change are dominated by a series of local entropy fluctuations affecting the global structure yet are mediated by only a few key residues. Transitional Dynamic Analysis (TDA) is a new method to detect these changes in local protein flexibility between different conformations arising from, for example, ligand binding. Additionally, Positional Impact Vertex for Entropy Transfer (PIVET) uses TDA to identify important residue contact changes that have a large impact on global fluctuation. We demonstrate the utility of these methods for Cyclin-dependent kinase 2 (CDK2), a system with crystal structures of this protein in multiple functionally relevant conformations and experimental data revealing the importance of local fluctuation changes for protein function. Results TDA and PIVET successfully identified select residues that are responsible for conformation specific regional fluctuation in the activation cycle of Cyclin Dependent Kinase 2 (CDK2). The detected local changes in protein flexibility have been experimentally confirmed to be essential for the regulation and function of the kinase. The methodologies also highlighted possible errors in previous molecular dynamic simulations that need to be resolved in order to understand this key player in cell cycle regulation. Finally, the use of entropy compensation as a possible allosteric mechanism for protein function is reported for CDK2. Conclusion The methodologies embodied in TDA and PIVET provide a quick approach to identify local fluctuation change important for protein function and residue contacts that contributes to these changes. Further, these approaches can be used to check for possible errors in protein dynamic simulations and have the potential to facilitate a better understanding of the contribution of entropy to protein allostery and function.

Gu, Jenny; Bourne, Philip E

2007-01-01

64

Conformation of organic chain in phase transition of hybrid (Cl 2 H 25 NH 3 ) 2 MnCl 4  

Microsoft Academic Search

The structural change in phase transition of hybrid (Cl2H25NH3)2MnCl4 was investigated. The temperature and the structures of the phase transition is investigated by thermal gravimetry (TG) and\\u000a differential scanning calorimetry (DSC), infrared spectrum (IR) and X-ray diffraction (XRD). The results suggest that the\\u000a phase transition is reversible and the structural change arises from the conformation change of the organic chain.

Liling Guo; Yubing Sun; Ao Mei; Yadong Dai; Hanxing Liu

2008-01-01

65

Alkaline conformational transition and gated electron transfer with a Lys 79 --> his variant of iso-1-cytochrome c.  

PubMed

To probe the mechanism of the alkaline conformational transition and its effect on the dynamics of gated electron transfer (ET) reactions, a Lys 79 --> His (K79H) variant of iso-1-cytochrome c has been prepared. Guanidine hydrochloride denaturation monitored by circular dichroism and absorbance at 695 nm indicates that this variant unfolds from a partially unfolded state. The conformation of the wild type (WT) and K79H proteins was monitored at 695 nm from pH 2 to 11. These data indicate that acid unfolding is multi-state for both K79H and WT proteins and that the His 79-heme alkaline conformer is more stable than a previously reported His 73-heme alkaline conformer. Fast and slow phases are observed in the kinetics of the alkaline transition of the K79H variant. The pH dependence of the fast phase kinetic data shows that ionizable groups with pKa values near 6.8 and 9 modulate the formation of the His 79-heme alkaline conformer. The slow phase kinetic data are consistent with a single ionizable group with a pKa near 9.5 promoting the Lys 73-heme alkaline transition. In the broader context of data on the alkaline transition, ionization of the ligand replacing Met 80 appears to play a primary role in promoting the formation of the alkaline conformer, with other ionizable groups acting as secondary modulators. Intermolecular ET with hexaammineruthenium(II) chloride shows conformational gating due to both His 79-heme and Lys 73-heme alkaline conformers. Both the position and the nature of the alkaline state ligand modulate the dynamics of ET gating. PMID:17713929

Bandi, Swati; Baddam, Saritha; Bowler, Bruce E

2007-08-22

66

Dehydration from conserved stem regions is fundamental for ligand-dependent conformational transition of the adenine-specific riboswitch.  

PubMed

Conformational dynamics and observed equilibrium constants for ligand binding of the adenine-specific riboswitch (add-A riboswitch) in the absence of Mg(2+) and presence of various concentrations of poly-ethylene glycol having an average molecular weight of 200 indicated that 54.2 water molecules were released from P2 and P3 stem regions of the add-A riboswitch during conformational transition upon the binding of 2-aminopurine, an analog of the natural ligand adenine. PMID:22854864

Kumar, Vinit; Endoh, Tamaki; Murakami, Kentaro; Sugimoto, Naoki

2012-10-01

67

Evaluation of carboxylic acid-induced conformational transitions of ?-lactoglobulin: Comparison of the alcohol effects on ?-lactoglobulin  

Microsoft Academic Search

Conformational transitions of bovine ?-lactoglobulin A (?-LG) induced by carboxylic acid were systematically studied by steady-state tryptophan (Trp) fluorescence. The behavior of ?-LG denaturation depends upon the species and concentration of carboxylic acid, as well as on the pH of solutions. The order of the effectiveness of the respective carboxylic acids was described as follows: MeCOOHconformational change of

Bong-Kuk Lee; Toshinori Shimanouchi; Hiroshi Umakoshi; Ryoichi Kuboi

2006-01-01

68

Inherent flexibility and protein function: The open/closed conformational transition in the N-terminal domain of calmodulin  

NASA Astrophysics Data System (ADS)

The key to understand a protein's function often lies in its conformational dynamics. We develop a coarse-grained variational model to investigate the interplay between structural transitions, conformational flexibility, and function of the N-terminal calmodulin domain (nCaM). In this model, two energy basins corresponding to the ``closed'' apo conformation and ``open'' holo conformation of nCaM are coupled by a uniform interpolation parameter. The resulting detailed transition route from our model is largely consistent with the recently proposed EF?-scaffold mechanism in EF-hand family proteins. We find that the N-terminal parts of the calcium binding loops shows higher flexibility than the C-terminal parts which form this EF?-scaffold structure. The structural transition of binding loops I and II are compared in detail. Our model predicts that binding loop II, with higher flexibility and earlier structural change than binding loop I, dominates the open/closed conformational transition in nCaM.

Tripathi, Swarnendu; Portman, John J.

2008-05-01

69

Solvent dependence of the ultrafast ground state recovery dynamics of phenol blue  

Microsoft Academic Search

We have studied femtosecond ground state recovery dynamics of phenol blue (PB) by pump-probe spectroscopy with a time resolution of 33 fs. Multiexponential decay with time constants extending from 300 fs to 10 ps were observed. Some low frequency intramolecular quantum beats were also observed. Solvent dependence of these decays and beats are discussed.

Yutaka Nagasawa; Ayako Watanabe; Yoshito Ando; Tadashi Okada

2001-01-01

70

MM/PBSA analysis of molecular dynamics simulations of bovine beta-lactoglobulin: free energy gradients in conformational transitions?  

PubMed

The pH-driven opening and closure of beta-lactoglobulin EF loop, acting as a lid and closing the internal cavity of the protein, has been studied by molecular dynamics (MD) simulations and free energy calculations based on molecular mechanics/Poisson-Boltzmann (PB) solvent-accessible surface area (MM/PBSA) methodology. The forms above and below the transition pH differ presumably only in the protonation state of residue Glu89. MM/PBSA calculations are able to reproduce qualitatively the thermodynamics of the transition. The analysis of MD simulations using a combination of MM/PBSA methodology and the colony energy approach is able to highlight the driving forces implied in the transition. The analysis suggests that global rearrangements take place before the equilibrium local conformation is reached. This conclusion may bear general relevance to conformational transitions in all lipocalins and proteins in general. PMID:15690343

Fogolari, Federico; Moroni, Elisabetta; Wojciechowski, Marcin; Baginski, Maciej; Ragona, Laura; Molinari, Henriette

2005-04-01

71

Effect of cationic surfactants on the conformational transition of poly(methacrylic acid)  

SciTech Connect

The interaction between poly(methacrylic acid) and alkyltrimethylammonium bromide, C/sub n/TAB, cationic surfactants has been investigated in aqueous solutions of pH 8, by use of the photophysics of pyrene and its derivatives. Photophysical studies of these fluorescent probes, both steady-state and pulsed laser studies, show that a conformational transition of PMA is induced by C/sub n/TAB. The surfactant induces a coiling up of PMA chains at pH 8, which takes place via a cooperative process. This effect takes place when the concentration of C/sub n/TAB is above a critical aggregate concentration, CAC. The CAC is 1 or 2 orders of magnitude less than the cmc of the corresponding micelle. There is significant effect of surfactant chain length and PMA concentration on the CAC, which provides information on the nature of the CAC and the mechanism of the PMA transition. A model is suggested for the aggregation of PMA-C/sub 10/TAB based on experimental data. Studies show that the aggregate consists of about 100 C/sub 10/TAB molecules and 1 coiled polymer chain.

Chu, D.; Thomas, J.K.

1986-10-01

72

Quantum chemical study of conformational preferences of intermediates and transition states in the alkaline hydrolysis of dimethyl phosphate  

NASA Astrophysics Data System (ADS)

The phosphate diester is a basic structure in DNA and RNA. The mechanism of phosphate diester hydrolysis is important for understanding the decomposition reactions of nucleic acids. In this study, we have explored the reaction pathway of alkaline hydrolysis of dimethyl phosphate, which is the simplest phosphate diester, with a hydroxide ion. Since the conformations of the intermediates and transition states reportedly influence the reaction mechanism of transacylation of methyl acetate with methoxide, we considered the conformational preferences on the alkaline hydrolysis of dimethyl phosphate, by using the most stable conformer as a reactant. Upon the reaction with hydroxide, a concerted reaction pathway was obtained in the gas phase, whereas a stepwise reaction pathway was obtained in water. As compared to the earlier study, our computation shows more stable conformations in the hydrolysis reactions than the previous study.

Takano, Y.; Kita, M.; Nakamura, H.

2013-08-01

73

Reentrant conformational transition of polyelectrolyte network in water alcohol mixtures in the presence of oppositely charged surfactant  

Microsoft Academic Search

Reentrant conformational transitions are observed in polyelectrolyte networks of sodium methacrylate-acrylamide copolymers in water-alcohol mixtures in the presence of cetylpyridinium bromide. At low alcohol content, gel shrinking is induced by complex formation between charged network and oppositely charged surfactant. In media with high alcohol content the complex dissociates and the collapse comes as a result of volume interactions between charged

E. E. Machaeva; S. G. Starodubtzev

1993-01-01

74

Ligand-induced conformational transitions and secondary-structure composition of chicken liver pyruvate carboxylase  

PubMed Central

Apparent conformational transitions induced in chicken liver pyruvate carboxylase by substrates, KHCO3 and MgATP, and the allosteric effector, acetyl-CoA, were studied by using the fluorescent probe, 8-anilinonaphthalene-1-sulphonic acid and c.d. Fluorescence measurements were made with both conventional and stopped-flow spectrophotometers. Additions of acetyl-CoA and/or ATP to the enzyme-probe solutions quenched fluorescence of the probe by the following cumulative amounts regardless of the sequence of additions: acetyl-CoA, 10–13%; ATP, 21–24%; acetyl-CoA plus ATP, about 35%. Additions of KHCO3 had no effect on the fluorescence. The rates of quenching by acetyl-CoA and MgATP (in the presence of acetyl-CoA) were too rapid to measure by stopped-flow kinetic methods, but kinetics of the MgATP effect (in the absence of acetyl-CoA) indicate three unimolecular transitions after the association step. The negligible effect of the probe on enzyme catalytic activity, a preservation of the near-u.v. c.d. effect of MgATP and acetyl-CoA in the presence of the probe and no observable unimolecular transitions after binding of the probe to the enzyme indicate that the probe had no deleterious effect on the enzyme. In contrast with results with 8-anilinonaphthalene-1-sulphonic acid, fluorescence of the ?-derivative of acetyl-CoA or ATP [fluorescent analogues; Secrist, Barrio, Leonard & Weber (1972) Biochemistry 11, 3499–3506] was not changed when either one was added to the enzyme. Secondary-structure composition of chicken liver pyruvate carboxylase estimated from the far-u.v. c.d. spectrum of the enzyme is 27% helix, 7% ?-pleated sheet and 66% other structural types.

McGurk, Karen S.; Spivey, H. Olin

1979-01-01

75

Fourier Imaging Correlation Spectroscopy for Studies of Sub-Cellular Dynamics and Biomolecular Conformation Transition Pathways  

NASA Astrophysics Data System (ADS)

Novel high signal-to-noise spectroscopic experiments that probe the dynamics of fluorescently labeled macromolecules have the potential to reveal complex intracellular biochemical mechanisms, or the slow relaxations of soft matter systems. Fourier imaging correlation spectroscopy (FICS) is a phase-selective approach to fluorescence fluctuation spectroscopy that employs a unique route to elevate signal levels while acquiring detailed information about microscopic coordinate trajectories. In this talk, I will illustrate the broad applicability of this approach by discussing two recent studies. The anomalous sub-diffusive dynamics of mitochondria in budding yeast are characterized using FICS, and provide detailed, length-scale dependent information about the influence of specific cytoskeletal elements on the movements of this organelle. We find that non-equilibrium forces associated with actin polymerization lead to a 1.5-fold enhancement of the long-time mitochondrial diffusion coefficient, and a transient sub-diffusive temporal scaling of the mean-square displacement. These non-equilibrium dynamics are a predominant factor in driving mitochondrial transport. In another set of experiments, polarization-modulated FICS simultaneously captures information about the internal conformation fluctuations and molecular translational dynamics of the fluorescent protein DsRed. By implementing a four-point correlation analysis, we construct two-dimensional spectral densities and joint distribution functions that determine temporal correlations of center-of-mass and anisotropy coordinates over successive time intervals. These four-point functions reveal statistically meaningful transition pathways between different optical conformations of the DsRed protein. The FICS method is well suited to investigate the dynamics of a broad range of heterogeneous systems, which include the molecular motions of glass forming liquids.

Marcus, Andrew

2010-03-01

76

Conformational transition of Sec machinery inferred from bacterial SecYE structures  

PubMed Central

Over 30% of proteins are secreted across or integrated into membranes. Their newly synthesized forms contain either cleavable signal sequences or non-cleavable membrane anchor sequences, which direct them to the evolutionarily conserved Sec translocon (SecYEG in prokaryotes and Sec61, comprising ?-, ?- and ?-subunits, in eukaryotes). The translocon then functions as a protein-conducting channel1. These processes of protein localization occur either at or after translation. In bacteria, the SecA ATPase2,3 drives post-translational translocation. The only high-resolution structure of a translocon available so far is that for SecYE? from the archaeon Methanococcus jannaschii4, which lacks SecA. Here we present the 3.2-Å-resolution crystal structure of the SecYE translocon from a SecA-containing organism, Thermus thermophilus. The structure, solved as a complex with an anti-SecY Fab fragment, revealed a ‘pre-open’ state of SecYE, in which several transmembrane helices are shifted, as compared to the previous SecYE? structure4, to create a hydrophobic crack open to the cytoplasm. Fab and SecA bind to a common site at the tip of the cytoplasmic domain of SecY. Molecular dynamics and disulphide mapping analyses suggest that the pre-open state might represent a SecYE conformational transition that is inducible by SecA binding. Moreover, we identified a SecA–SecYE interface that comprises SecA residues originally buried inside the protein, indicating that both the channel and the motor components of the Sec machinery undergo cooperative conformational changes on formation of the functional complex.

Tsukazaki, Tomoya; Mori, Hiroyuki; Fukai, Shuya; Ishitani, Ryuichiro; Mori, Takaharu; Dohmae, Naoshi; Perederina, Anna; Sugita, Yuji; Vassylyev, Dmitry G.; Ito, Koreaki; Nureki, Osamu

2008-01-01

77

Computation of conformational transitions in proteins by virtual atom molecular mechanics as validated in application to adenylate kinase.  

PubMed

Many proteins function through conformational transitions between structurally disparate states, and there is a need to explore transition pathways between experimentally accessible states by computation. The sizes of systems of interest and the scale of conformational changes are often beyond the scope of full atomic models, but appropriate coarse-grained approaches can capture significant features. We have designed a comprehensive knowledge-based potential function based on a C alpha representation for proteins that we call the virtual atom molecular mechanics (VAMM) force field. Here, we describe an algorithm for using the VAMM potential to describe conformational transitions, and we validate this algorithm in application to a transition between open and closed states of adenylate kinase (ADK). The VAMM algorithm computes normal modes for each state and iteratively moves each structure toward the other through a series of intermediates. The move from each side at each step is taken along that normal mode showing greatest engagement with the other state. The process continues to convergence of terminal intermediates to within a defined limit--here, a root-mean-square deviation of 1 A. Validations show that the VAMM algorithm is highly effective, and the transition pathways examined for ADK are compatible with other structural and biophysical information. We expect that the VAMM algorithm can address many biological systems. PMID:19706894

Korkut, Anil; Hendrickson, Wayne A

2009-08-25

78

Extensive conformational transitions are required to turn on ATP hydrolysis in myosin  

PubMed Central

Conventional myosin is representative of biomolecular motors in which the hydrolysis of Adenosine triphosphate (ATP) is coupled to large-scale structural transitions both in and remote from the active site. The mechanism that underlies such “mechanochemical coupling”, especially the causal relationship between the hydrolysis and the allosteric structural changes, has remained elusive despite extensive experimental and computational analyses. In this study, using combined quantum mechanical and molecular mechanical (QM/MM) simulations and different conformations of the myosin motor domain, we provide evidence to support that regulation of ATP hydrolysis activity is not limited to residues in the immediate environment of the ? phosphate. Specifically, we illustrate that efficient hydrolysis of ATP depends not only on the proper orientation of the lytic water but also the structural stability of several nearby residues, especially the Arg238-Glu459 salt-bridge (the numbering of residues follows the myosin II in Dictyostelium discoideum) and the water molecule that spans this salt-bridge and the lytic water. More importantly, by comparing the hydrolysis activity in two motor conformations with very similar active site (i.e., Switch-I and II) configurations, which distinguishes this work from our previous study, the results clearly indicate that the ability of these residues to make their crucial electrostatic stabilization relies on the configuration of residues in the nearby N-terminus of the relay helix and the “wedge loop”. Without the structural support from those motifs, residues in a closed active site in the post-rigor motor domain undergo subtle structural variations that lead to consistently higher calculated ATP hydrolysis barriers than in the pre-powerstroke state. In other words, starting from the post-rigor state, turning on the ATPase activity requires not only displacement of Switch II to close the active site but also structural transitions in the N-terminus of the relay helix and the “wedge loop”, which have been proposed previously to be ultimately coupled to the rotation of the converter subdomain 40 Å away.

Yang, Yang; Yu, Haibo; Cui, Qiang

2009-01-01

79

Effect of ?-electron conjugation length on the solvent-dependent S 1 lifetime of peridinin  

NASA Astrophysics Data System (ADS)

Peridinin exhibits an anomalous solvent dependence of its S 1 excited state lifetime attributed to the presence of an intramolecular charge transfer (ICT) state. The nature of this state has yet to be elucidated. Ultrafast time-resolved optical spectroscopy has been performed on a synthetic analog, C 35-peridinin, having one less conjugated double bond than peridinin. The data reveal the lifetime decreases from 1.5 ns in n-hexane to 9.2 ps in methanol, an order of magnitude larger than peridinin. This is the strongest solvent dependence on the lifetime of an S 1 state of a carotenoid yet reported. The data support the view that the S 1 and ICT states are strongly coupled.

Chatterjee, Nirmalya; Niedzwiedzki, Dariusz M.; Kajikawa, Takayuki; Hasegawa, Shinji; Katsumura, Shigeo; Frank, Harry A.

2008-09-01

80

Solvent dependent Raman bandshape analysis on CO containing molecules: vibrational relaxation study.  

PubMed

Solvent dependent Raman band studies of some carbonyl containing molecules have been carried out in chlorobenzene (CLB) and chloroform (CLF) solvents. The variation of bandwidth with the solvent concentration was discussed using different mechanisms. The vibrational and reorientational correlation times were studied corresponding to solvent concentrations. The reorientational correlation time follows with the liquid viscosity in molecules under study. It reflects about the nature of solvent molecules hindering to the orientational motion of solute in liquid solution. PMID:22366620

Gomti Devi, Th; Upadhayay, Ganesh

2012-02-02

81

Kinetics of chain collapse in dilute polymer solutions: Molecular weight and solvent dependences  

Microsoft Academic Search

The molecular weight and solvent dependences of the characteristic time of chain collapse were studied for poly(methyl methacrylate) (PMMA) of the molecular weight Mw=6.4×106 and 1.14×107 in pure acetonitrile (AcN) and in the mixed solvent of AcN+water (10 vol %). The size of PMMA chains was measured as a function of the time after the quench by static light scattering

Yasuyuki Maki; Toshiaki Dobashi; Mitsuo Nakata

2007-01-01

82

An Intracellular Interaction Network Regulates Conformational Transitions in the Dopamine Transporter*S?  

PubMed Central

Neurotransmitter:sodium symporters (NSS)1 mediate sodium-dependent reuptake of neurotransmitters from the synaptic cleft and are targets for many psychoactive drugs. The crystal structure of the prokaryotic NSS protein, LeuT, was recently solved at high resolution; however, the mechanistic details of regulation of the permeation pathway in this class of proteins remain unknown. Here we combine computational modeling and experimental probing in the dopamine transporter (DAT) to demonstrate the functional importance of a conserved intracellular interaction network. Our data suggest that a salt bridge between Arg-60 in the N terminus close to the cytoplasmic end of transmembrane segment (TM) 1 and Asp-436 at the cytoplasmic end of TM8 is stabilized by a cation-? interaction between Arg-60 and Tyr-335 at the cytoplasmic end of TM6. Computational probing illustrates how the interactions may determine the flexibility of the permeation pathway, and mutagenesis within the network and results from assays of transport, as well as the state-dependent accessibility of a substituted cysteine in TM3, support the role of this network in regulating access between the substrate binding site and the intracellular milieu. The mechanism that emerges from these findings may be unique to the NSS family, where the local disruption of ionic interactions modulates the transition of the transporter between the outward- and inward-facing conformations.

Kniazeff, Julie; Shi, Lei; Loland, Claus J.; Javitch, Jonathan A.; Weinstein, Harel; Gether, Ulrik

2008-01-01

83

A soft-modeling approach to interpret thermodynamic and conformational transitions of polynucleotides.  

PubMed

Multivariate outputs from the experimental monitoring of biochemical processes are usually difficult to interpret applying methods based on a priori chemical models. Curve resolution methods are model-free procedures, generally known as soft-modeling methods, which obtain the concentration profiles and instrumental responses of each individual species involved in a multivariate monitored process without making any kind of external assumption. Of the curve resolution methods available, the alternating least squares (ALS) is proposed here because of its ability to operate on one or on several matrices. Furthermore, ALS allows the introduction of information related to the internal data structure and to the general features of the concentration profiles and instrumental responses through the input of suitable constraints in the iterative resolution procedure. The ALS potential is tested on several data sets coming from the multivariate spectrometric monitoring of polyuridylic (polyU), polycytidylic (polyC), and polyadenylic (polyA) protonation equilibria in dioxane/water 30% (v/v). Information concerning the evolution of the concentration profiles and the spectra of each individual species involved in the acid-base equilibria, the presence and pattern of polyelectrolyte effects, and the presence of conformational transitions associated or not with the proton uptake process is presented. PMID:9414208

de Juan, A; Izquierdo-Ridorsa, A; Tauler, R; Fonrodona, G; Casassas, E

1997-12-01

84

A stripe-to-droplet transition driven by conformational transitions in a binary lipid-lipopolymer mixture at the air-water interface.  

PubMed

We report the observation of an unusual stripe-droplet transition in precompressed Langmuir monolayers consisting of mixtures of poly(ethylene) glycol (PEG) amphiphiles and phospholipids. This highly reproducible and fully reversible transition occurs at approximately zero surface pressure during expansion (or compression) of the monolayer following initial compression into a two-dimensional solid phase. It is characterized by spontaneous emergence of an extended, disordered stripe-like morphology from an optically homogeneous phase during gradual expansion. These stripe patterns appear as a transient feature and continuously progress, involving gradual coarsening and ultimate transformation into a droplet morphology upon further expansion. Furthermore, varying relative concentrations of the two amphiphiles and utilizing amphiphiles with considerably longer ethylene glycol headgroups reveal that this pattern evolution occurs in narrow concentration regimes, values of which depend on ethylene oxide headgroup size. These morphological transitions are reminiscent of those seen during a passage through a critical point by variations in thermodynamic parameters (e.g., temperature or pressure) as well as those involving spinodal decomposition. While the precise mechanism cannot be ascertained using present experiments alone, our observations can be reconciled in terms of modulations in competing interactions prompted by the pancake-mushroom-brush conformational transitions of the ethylene glycol headgroup. This in turn suggests that the conformational degree of freedom represents an independent order parameter, or a switch, which can induce large-scale structural reorganization in amphiphilic monolayers. Because molecular conformational changes are pervasive in biological membranes, we speculate that such conformational transition-induced pattern evolution might provide a physical mechanism by which membrane processes are amplified. PMID:21244080

El-Khouri, Rita J; Frey, Shelli L; Szmodis, Alan W; Hall, Emily; Kauffman, Karlina J; Patten, Timothy E; Lee, Ka Yee C; Parikh, Atul N

2011-01-18

85

An analysis of stable forms of CL-20: A DFT study of conformational transitions, infrared and Raman spectra  

NASA Astrophysics Data System (ADS)

The most stable forms of 2,4,6,8,10,12-hexanitro-2,4,6,8,10,12-hexaazaisowurtzitane (CL-20) were analyzed at the B3LYP/6-31G+(d,p) level of theory. The mechanism of conformational transformations was clarified. The activation energies of those transitions were found to be quite low and lie in the range 1.2 4.0 kcal mol-1. IR and Raman spectra of the studied CL-20 forms were simulated. The predicted vibrational modes were used for comparison with the experimental values. The unique peaks for each of the conformers in IR and Raman spectra were found. These peaks can be used as the “signatures” of the studied conformers and for identification of different polymorphs of CL-20 in mixtures.

Kholod, Yana; Okovytyy, Sergiy; Kuramshina, Gulnara; Qasim, Mohammad; Gorb, Leonid; Leszczynski, Jerzy

2007-10-01

86

All-or-none switching of transcriptional activity on single DNA molecules caused by a discrete conformational transition  

NASA Astrophysics Data System (ADS)

Recently, it has been confirmed that long duplex DNA molecules with a size larger than several tens of kilo-base pairs (kbp), exhibit a discrete conformational transition from an unfolded coil state to a folded compact state upon the addition of various kinds of chemical species that usually induce DNA condensation. In this study, we performed a single-molecule observation on a large DNA, Lambda ZAP II DNA (~41 kbp), in a solution containing RNA polymerase and substrates along with spermine, a tetravalent cation, at different concentrations, by use of fluorescence staining of both DNA and RNA. We found that transcription, or RNA production, is completely inhibited in the compact globule state, but is actively performed in the unfolded coil state. Such an all-or-none effect on transcriptional activity induced by the discrete conformational transition of single DNA molecules is discussed in relation to the mechanism of the regulation of large-scale genetic activity.

Yamada, Ayako; Kubo, Koji; Nakai, Tonau; Yoshikawa, Kenichi; Tsumoto, Kanta

2005-05-01

87

Reduced-Amide Inhibitor of Pin1 Binds in a Conformation Resembling a Twisted-Amide Transition State†  

PubMed Central

The mechanism of the cell cycle regulatory peptidyl prolyl isomerase (PPIase), Pin1, was investigated using reduced-amide inhibitors designed to mimic the twisted-amide transition state. Inhibitors, R–pSer–?[CH2N]–Pro–2-(indol-3-yl)-ethylamine, 1 (R = fluorenylmethoxycarbonyl, Fmoc), and 2 (R = Ac), of Pin1 were synthesized and bioassayed. Inhibitor 1 had an IC50 value of 6.3 ?M, which is 4.5-fold better inhibition for Pin1 than our comparable ground state analogue, a cis-amide alkene isostere containing inhibitor. The change of Fmoc to Ac in 2 improved aqueous solubility for structural determination, and resulted in an IC50 value of 12 ?M. The X-ray structure of the complex of 2 bound to Pin1 was determined to 1.76 Å resolution. The structure revealed that the reduced amide adopted a conformation similar to the proposed twisted-amide transition state of Pin1, with a trans-pyrrolidine conformation of the prolyl ring. A similar conformation of substrate would be destabilized relative to the planar amide conformation. Three additional reduced amides, with Thr replacing Ser, and l- or d-pipecolate (Pip) replacing Pro, were slightly weaker inhibitors of Pin1.

Xu, Guoyan G.; Zhang, Yan; Mercedes-Camacho, Ana Y.; Etzkorn, Felicia A.

2011-01-01

88

Free energy of conformational transition paths in biomolecules: The string method and its application to myosin VI  

PubMed Central

A set of techniques developed under the umbrella of the string method is used in combination with all-atom molecular dynamics simulations to analyze the conformation change between the prepowerstroke (PPS) and rigor (R) structures of the converter domain of myosin VI. The challenges specific to the application of these techniques to such a large and complex biomolecule are addressed in detail. These challenges include (i) identifying a proper set of collective variables to apply the string method, (ii) finding a suitable initial string, (iii) obtaining converged profiles of the free energy along the transition path, (iv) validating and interpreting the free energy profiles, and (v) computing the mean first passage time of the transition. A detailed description of the PPS?R transition in the converter domain of myosin VI is obtained, including the transition path, the free energy along the path, and the rates of interconversion. The methodology developed here is expected to be useful more generally in studies of conformational transitions in complex biomolecules.

Ovchinnikov, Victor; Karplus, Martin; Vanden-Eijnden, Eric

2011-01-01

89

Dynamics of the His79-Heme Alkaline Transition of Yeast Iso-1-cytochrome c Probed by Conformationally Gated Electron Transfer with Co(II)bis(terpyridine).  

PubMed

Alkaline conformers of cytochrome c may be involved in both its electron transport and apoptotic functions. We use cobalt(II)bis(terpyridine), Co(terpy)2(2+), as a reagent for conformationally gated electron-transfer (gated ET) experiments to study the alkaline conformational transition of K79H variants of yeast iso-1-cytochrome c expressed in Escherichia coli , WT*K79H, with alanine at position 72 and Saccharomyces cerevisiae , yK79H, with trimethyllysine (Tml) at position 72. Co(terpy)2(2+) is well-suited to the 100 ms to 1 s time scale of the His79-mediated alkaline conformational transition of these variants. Reduction of the His79-heme alkaline conformer by Co(terpy)2(2+) occurs primarily by gated ET, which involves conversion to the native state followed by reduction, with a small fraction of the His79-heme alkaline conformer directly reduced by Co(terpy)2(2+). The gated ET experiments show that the mechanism of formation of the His79-heme alkaline conformer involves only two ionizable groups. In previous work, we showed that the mechanism of the His73-mediated alkaline conformational transition requires three ionizable groups. Thus, the mechanism of heme crevice opening depends upon the position of the ligand mediating the process. The microscopic rate constants provided by gated ET studies show that mutation of Tml72 (yK79H variant) in the heme crevice loop to Ala72 (WT*K79H variant) affects the dynamics of heme crevice opening through a small destabilization of both the native conformer and the transition state relative to the His79-heme alkaline conformer. Previous pH jump data had indicated that the Tml72?Ala mutation primarily stabilized the transition state for the His79-mediated alkaline conformational transition. PMID:23899348

Cherney, Melisa M; Junior, Carolyn C; Bergquist, Bryan B; Bowler, Bruce E

2013-08-15

90

Size- and solvent-dependent kinetics for cis- trans isomerization in donor-acceptor systems  

NASA Astrophysics Data System (ADS)

We have investigated, using time-resolved and steady-state optical spectroscopy, the cis- trans isomerization dynamics in a series of charge transfer, donor-acceptor compounds. The number of donor (dithiafulvene) and acceptor ( p-nitrophenyl) moieties as well as their spatial arrangement around a central ethynylethene core has been varied in a systematic way. All compounds in the series are weakly fluorescent. We show that the fluorescence spectrum red-shifts within a few picoseconds, a shift which occurs concurrently with a blue-shift of the transient absorption spectrum. The kinetics following the initial relaxation are in all cases multi-exponential, and the time constants correlate with molecular size and solvent viscosity. We interpret the data as a result of conformational change where the conjugation through the central double bond is broken upon excitation into the charge-transfer transition, and the time for rotation around this bond is dependent on the molecular interactions between solute and solvent.

Becker, Hans-Christian; Kilså, Kristine

2009-06-01

91

Analysis and elimination of a bias in targeted molecular dynamics simulations of conformational transitions: application to calmodulin.  

PubMed

The popular targeted molecular dynamics (TMD) method for generating transition paths in complex biomolecular systems is revisited. In a typical TMD transition path, the large-scale changes occur early and the small-scale changes tend to occur later. As a result, the order of events in the computed paths depends on the direction in which the simulations are performed. To identify the origin of this bias, and to propose a method in which the bias is absent, variants of TMD in the restraint formulation are introduced and applied to the complex open ? closed transition in the protein calmodulin. Due to the global best-fit rotation that is typically part of the TMD method, the simulated system is guided implicitly along the lowest-frequency normal modes, until the large spatial scales associated with these modes are near the target conformation. The remaining portion of the transition is described progressively by higher-frequency modes, which correspond to smaller-scale rearrangements. A straightforward modification of TMD that avoids the global best-fit rotation is the locally restrained TMD (LRTMD) method, in which the biasing potential is constructed from a number of TMD potentials, each acting on a small connected portion of the protein sequence. With a uniform distribution of these elements, transition paths that lack the length-scale bias are obtained. Trajectories generated by steered MD in dihedral angle space (DSMD), a method that avoids best-fit rotations altogether, also lack the length-scale bias. To examine the importance of the paths generated by TMD, LRTMD, and DSMD in the actual transition, we use the finite-temperature string method to compute the free energy profile associated with a transition tube around a path generated by each algorithm. The free energy barriers associated with the paths are comparable, suggesting that transitions can occur along each route with similar probabilities. This result indicates that a broad ensemble of paths needs to be calculated to obtain a full description of conformational changes in biomolecules. The breadth of the contributing ensemble suggests that energetic barriers for conformational transitions in proteins are offset by entropic contributions that arise from a large number of possible paths. PMID:22409258

Ovchinnikov, Victor; Karplus, Martin

2012-03-28

92

Analysis and Elimination of a Bias in Targeted Molecular Dynamics Simulations of Conformational Transitions: Application to Calmodulin  

PubMed Central

The popular targeted molecular dynamics (TMD) method for generating transition paths in complex biomolecular systems is revisited. In a typical TMD transition path, the large-scale changes occurring early, and the small-scale changes tend to occur later. As a result, the order of events in the computed paths depends on the direction in which the simulations are performed. To identify the origin of this bias, and to propose a method in which the bias is absent, variants of TMD in the restraint formulation are introduced and applied to the complex Open?Closed transition in the protein Calmodulin. Due to the global best-fit rotation that is typically part of the TMD method, the simulated system is guided implicitly along the lowest-frequency normal modes, until the large spatial scales associated with these modes are near the target conformation. The remaining portion of the transition is described progressively by higher-frequency modes, which correspond to smaller-scale rearrangements. A straightforward modification of TMD that avoids the global best-fit rotation is the locally restrained TMD (LRTMD) method, in which the biasing potential is constructed from a number of TMD potentials, each acting on a small connected portion of the protein sequence. With a uniform distribution of these elements, transition paths that lack the length-scale bias are obtained. Trajectories generated by steered MD in dihedral angle space (DSMD), a method that avoids best-fit rotations altogether, also lack the length-scale bias. To examine the importance of the paths generated by TMD, LRTMD, and DSMD in the actual transition, we use the finite-temperature string method to compute the free energy profile associated with a transition tube around a path generated by each algorithm. The free energy barriers associated with the paths are comparable, suggesting that transitions can occur along each route with similar probabilities. This result indicates that a broad ensemble of paths needs to be calculated to obtain a full description of conformational changes in biomolecules. The breadth of the contributing ensemble suggests that energetic barriers for conformational transitions in proteins are offset by entropic contributions that arise from a large number of possible paths.

Ovchinnikov, Victor; Karplus, Martin

2012-01-01

93

Solvent-dependent luminescent Cu(I) framework based on 5-(4-pyridyl)tetrazole  

SciTech Connect

A new Cu(IOTA) coordination compound, Cu{sub 4}(L){sub 4}.2EtOH (1), has been obtained from the solvothermal reaction of CuBr, HL (L=5-(4-pyridyl) tetrazole), EtOH and NH{sub 3}.H{sub 2}O. The structure determination reveals that 1 has a 2D network, where each Cu(I) atom adopts a trigonal coordination mode. The 2D networks stacked in an ABAB sequence through the pi-pi interaction to form a 3D supramolecular framework, giving a 1D channel along the b-axis. The TGA and powder XRD measurements reveal that the framework is stable after removal of the guest molecules. Gas (N{sub 2}) adsorption measurement was carried out for the framework. Framework 1 shows II sorption profile with N{sub 2}, which indicates that N{sub 2} molecules cannot diffuse into the micropore and only surface adsorption occurs. The photoluminescent research shows that compound 1 displays an interesting solvent-dependent luminescence. - Abstract: A new Cu(I) compound, Cu{sub 4}(L){sub 4}.2EtOH (1) (L=5-(4-pyridyl) tetrazole), was synthesized under solvothermal method, which displays an interesting solvent-dependent luminescence. Display Omitted

Wang Fei; Yu Rongmin; Zhang Qisheng; Zhao Zhenguo; Wu Xiaoyuan; Xie Yiming; Qin Li; Chen Shanci [State Key Laboratory of Structural Chemistry, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, Fujian 35002 (China); Lu Canzhong, E-mail: czlu@fjirsm.ac.c [State Key Laboratory of Structural Chemistry, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, Fujian 35002 (China)

2009-09-15

94

A Conformational Transition in the Myosin VI Converter Contributes to the Variable Step Size  

PubMed Central

Myosin VI (MVI) is a dimeric molecular motor that translocates backwards on actin filaments with a surprisingly large and variable step size, given its short lever arm. A recent x-ray structure of MVI indicates that the large step size can be explained in part by a novel conformation of the converter subdomain in the prepowerstroke state, in which a 53-residue insert, unique to MVI, reorients the lever arm nearly parallel to the actin filament. To determine whether the existence of the novel converter conformation could contribute to the step-size variability, we used a path-based free-energy simulation tool, the string method, to show that there is a small free-energy difference between the novel converter conformation and the conventional conformation found in other myosins. This result suggests that MVI can bind to actin with the converter in either conformation. Models of MVI/MV chimeric dimers show that the variability in the tilting angle of the lever arm that results from the two converter conformations can lead to step-size variations of ?12 nm. These variations, in combination with other proposed mechanisms, could explain the experimentally determined step-size variability of ?25 nm for wild-type MVI. Mutations to test the findings by experiment are suggested.

Ovchinnikov, V.; Cecchini, M.; Vanden-Eijnden, E.; Karplus, M.

2011-01-01

95

Conformational Transitions in RNA Single Uridine and Adenosine Bulge Structures: A Molecular Dynamics Free Energy Simulation Study  

PubMed Central

Extra unmatched nucleotides (single base bulges) are common structural motifs in folded RNA molecules and can participate in RNA-ligand binding and RNA tertiary structure formation. Often these processes are associated with conformational transitions in the bulge region such as flipping out of the bulge base from an intrahelical stacked toward a looped out state. Knowledge of the flexibility of bulge structures and energetics of conformational transitions is an important prerequisite to better understand the function of this RNA motif. Molecular dynamics simulations were performed on single uridine and adenosine bulge nucleotides at the center of eight basepair RNA molecules and indicated larger flexibility of the bulge bases compared to basepaired regions. The umbrella sampling method was applied to study the bulge base looping out process and accompanying conformational and free energy changes. Looping out toward the major groove resulted in partial disruption of adjacent basepairs and was found to be less favorable compared to looping out toward the minor groove. For both uridine and adenosine bulges, a positive free energy change for full looping out was obtained which was ?1.5 kcal mol?1 higher in the case of the adenosine compared to the uridine bulge system. The simulations also indicated stable partially looped out states with the bulge bases located in the RNA minor groove and forming base triples with 5?-neighboring basepairs. In the case of the uridine bulge this state was more stable than the intrahelical stacked bulge structure. Induced looping out toward the minor groove involved crossing of an energy barrier of ?3.5 kcal mol?1 before reaching the base triple state. A continuum solvent analysis of intermediate bulge states indicated that electrostatic interactions stabilize looped out and base triple states, whereas van der Waals interactions and nonpolar contributions favor the stacked bulge conformation.

Barthel, Andre; Zacharias, Martin

2006-01-01

96

Conformational transitions in RNA single uridine and adenosine bulge structures: a molecular dynamics free energy simulation study.  

PubMed

Extra unmatched nucleotides (single base bulges) are common structural motifs in folded RNA molecules and can participate in RNA-ligand binding and RNA tertiary structure formation. Often these processes are associated with conformational transitions in the bulge region such as flipping out of the bulge base from an intrahelical stacked toward a looped out state. Knowledge of the flexibility of bulge structures and energetics of conformational transitions is an important prerequisite to better understand the function of this RNA motif. Molecular dynamics simulations were performed on single uridine and adenosine bulge nucleotides at the center of eight basepair RNA molecules and indicated larger flexibility of the bulge bases compared to basepaired regions. The umbrella sampling method was applied to study the bulge base looping out process and accompanying conformational and free energy changes. Looping out toward the major groove resulted in partial disruption of adjacent basepairs and was found to be less favorable compared to looping out toward the minor groove. For both uridine and adenosine bulges, a positive free energy change for full looping out was obtained which was approximately 1.5 kcal mol-1 higher in the case of the adenosine compared to the uridine bulge system. The simulations also indicated stable partially looped out states with the bulge bases located in the RNA minor groove and forming base triples with 5'-neighboring basepairs. In the case of the uridine bulge this state was more stable than the intrahelical stacked bulge structure. Induced looping out toward the minor groove involved crossing of an energy barrier of approximately 3.5 kcal mol-1 before reaching the base triple state. A continuum solvent analysis of intermediate bulge states indicated that electrostatic interactions stabilize looped out and base triple states, whereas van der Waals interactions and nonpolar contributions favor the stacked bulge conformation. PMID:16399833

Barthel, André; Zacharias, Martin

2006-01-06

97

Reversible switching of fluorophore property based on intrinsic conformational transition of adenylate kinase during its catalytic cycle.  

PubMed

Adenylate kinase shows a conformational transition (OPEN and CLOSED forms) during substrate binding and product release to mediate the phosphoryl transfer between ADP and ATP/AMP. The protein motional characteristics will be useful to construct switching systems of fluorophore properties caused by the catalytic cycle of the enzyme. This paper demonstrates in situ reversible switching of a fluorophore property driven by the conformational transition of the enzyme. The pyrene-conjugated mutant adenylate kinase is able to switch the monomer/excimer emission property of pyrene on addition of ADP or P(1)P(5)-di(adenosine-5')pentaphosphate (Ap5A, a transition state analog). The observation under the dilute condition (~0.1 ?M) indicates that the emission spectral change was caused by the motion of a protein molecule and not led by protein-protein interactions through ?-? stacking of pyrene rings. The switching can be reversibly conducted by using hexokinase-coupling reaction. The fashion of the changes in emission intensities at various ligand concentrations is different between ADP, Mg(2+)-bound ADP, and Mg(2+)-bound Ap5A. The emission property switching is repeatable by a sequential addition of a substrate in a one-pot process. It is proposed that the property of a synthetic molecule on the enzyme surface is switchable in response to the catalytic cycle of adenylate kinase. PMID:23718926

Fujii, Akira; Hirota, Shun; Matsuo, Takashi

2013-06-11

98

Transition Metal-Mediated Liposomal Encapsulation of Irinotecan (CPT11) Stabilizes the Drug in the Therapeutically Active Lactone Conformation  

Microsoft Academic Search

Purpose  To determine whether entrapped transition metals could mediate the active encapsulation of the anticancer drug irinotecan\\u000a into preformed liposomes. Further, to establish that metal complexation could stabilize liposomal irinotecan in the therapeutically\\u000a active lactone conformation.\\u000a \\u000a \\u000a \\u000a Materials and Methods  Irinotecan was added to preformed 1,2-distearoyl-sn-glycero-phosphocholine\\/cholesterol (DSPC\\/chol) liposomes prepared in CuSO4, ZnSO4, MnSO4, or CoSO4 solutions, and drug encapsulation was determined over time.

Euan Ramsay; Jehan Alnajim; Malathi Anantha; Aman Taggar; Anitha Thomas; Katarina Edwards; Göran Karlsson; Murray Webb; Marcel Bally

2006-01-01

99

An analysis of stable forms of CL20: A DFT study of conformational transitions, infrared and Raman spectra  

Microsoft Academic Search

The most stable forms of 2,4,6,8,10,12-hexanitro-2,4,6,8,10,12-hexaazaisowurtzitane (CL-20) were analyzed at the B3LYP\\/6-31G+(d,p) level of theory. The mechanism of conformational transformations was clarified. The activation energies of those transitions were found to be quite low and lie in the range 1.2–4.0kcalmol?1. IR and Raman spectra of the studied CL-20 forms were simulated. The predicted vibrational modes were used for comparison with

Yana Kholod; Sergiy Okovytyy; Gulnara Kuramshina; Mohammad Qasim; Leonid Gorb; Jerzy Leszczynski

2007-01-01

100

Atomic layer deposition conformality and process optimization: Transitioning from 2-dimensional planar systems to 3-dimensional nanostructures  

NASA Astrophysics Data System (ADS)

Conformal coatings are becoming increasingly important as technology heads towards the nanoscale. The exceptional thickness control (atomic scale) and conformality (uniformity over nanoscale 3D features) of atomic layer deposition (ALD) has made it the process of choice for numerous applications found in microelectronics and nanotechnology with a wide variety of ALD processes and resulting materials. While its benefits derive from self-limited saturating surface reactions of alternating gas precursors, process optimization for ALD conformality is often difficult as process parameters, such as dosage, purge, temperature and pressure are often interdependent with one another, especially within the confines of an ultra-high aspect ratio nanopore. Therefore, processes must be optimized to achieve self-limiting saturated surfaces and avoid parasitic CVD-like reactions in order to maintain thickness control and achieve uniformity and conformality at the atomic level while preserving the desired materials' properties (electrical, optical, compositional, etc.). This work investigates novel approaches to optimize ALD conformality when transitioning from a 2D planar system to a 3D ultra-high aspect ratio nanopore in the context of a cross-flow wafer-scale reactor used to highlight deviations from ideal ALD behavior. Porous anodic alumina (PAA) is used as a versatile platform to analyze TiO2 ALD profiles via ex-situ SEM, EDS and TEM. Results of TiO2 ALD illustrate enhanced growth rates that can occur when the precursors titanium tetraisopropoxide and ozone were used at minimal saturation doses for ALD and for considerably higher doses. The results also demonstrate that ALD process recipes that achieve excellent across-wafer uniformity across full 100 mm wafers do not produce conformal films in ultra-high aspect ratio nanopores. The results further demonstrate that conformality is determined by precursor dose, surface residence time, and purge time, creating large depletion gradients down the length of the nanopore. Also, deposition of ALD films over sharp surface features are very uniform, and verified by profile evolution modeling. This behavior, in contrast to that in high aspect ratio structures, suggests strongly that detailed dynamics, local flow conditions (e.g. viscous vs molecular), surface residence time, and ALD surface reaction kinetics play a complex role in determining ALD profiles for high aspect ratio features.

Robertson Cleveland, Erin Darcy

101

Solvent dependency of rotational barriers in ethamivan and comparison to nikethamide.  

PubMed

Carbon-13 nuclear magnetic resonance (NMR) techniques were employed to examine the effects of solvent environment on rotational barriers in two drugs known to cause widespread stimulation in the mammalian central nervous system: ethamivan and nikethamide. Total NMR bandshape analysis was performed for the exchanging alkyl carbon resonances of these compounds as a function of temperature in six solvent systems: D2O, CH3OD, CH3CH2OD, CDCl3, C6D6 and CF3CH2OH. The rate constants for rotation about the amide bond obtained in this way were used to calculate free energy (delta G++), enthalpy (delta H++) and entropy (delta S++) of activation parameters for this process. Our results indicate that the magnitude of rotational barriers is affected markedly by (1) the size and polarity of the solvent molecules, and (2) the nature of the aromatic ring system attached to the amide grouping. Comparative interpretation of the thermodynamic parameters in light of the structures of nikethamide and ethamivan (in the various solvent systems examined) has further clarified the manner in which hydrogen bonding interactions between solvent molecules and the carbonyl oxygen of these analogues stabilize transition state conformers. PMID:2917015

Rosenthal, L S; Curran, E; Bean, J W; Nelson, D J

1989-02-15

102

Temperature induced Raman spectro-microscopy to detect phase transitions and associated changes in the conformational order of PEGylated lipids and liposomes  

Microsoft Academic Search

The study of phase transitions and associated changes in the conformational order of lipids is of importance in various research areas dealing with phenomena such as the formation and fusion of vesicles, trans-membrane diffusion and membrane interactions with drugs and proteins. 1 Several techniques have previously been employed to investigate lipid phase transitions, including differential scanning calorimetry (DSC), X-ray diffraction,

Rajan K. Bista; Reinhard F. Bruch; Aaron M. Covington; Alexander Sorger

103

Characterizing rapid, activity-linked conformational transitions in proteins via sub-second hydrogen deuterium exchange mass spectrometry.  

PubMed

This review outlines the application of time-resolved electrospray ionization mass spectrometry (TRESI-MS) and hydrogen-deuterium exchange (HDX) to study rapid, activity-linked conformational transitions in proteins. The method is implemented on a microfluidic chip which incorporates all sample-handling steps required for a 'bottom-up' HDX workflow: a capillary mixer for sub-second HDX labeling, a static mixer for HDX quenching, a microreactor for rapid protein digestion, and on-chip electrospray. By combining short HDX labeling pulses with rapid digestion, this approach provides a detailed characterization of the structural transitions that occur during protein folding, ligand binding, post-translational modification and catalytic turnover in enzymes. This broad spectrum of applications in areas largely inaccessible to conventional techniques means that microfluidics-enabled TRESI-MS/HDX is a unique and powerful approach for investigating the dynamic basis of protein function. PMID:23663649

Resetca, Diana; Wilson, Derek J

2013-06-11

104

Localization of E1-E2 conformational transitions of sarcoplasmic reticulum Ca-ATPase by tryptic cleavage and hydrophobic labeling.  

PubMed

Tryptic peptides of Ca-ATPase in E1 and E2 conformational states (Andersen, J. P., Jørgensen, P. L., J. Membrane Biol. 88:187-198 (1985] have been isolated by size exclusion high performance liquid chromatography in sodium dodecyl sulfate. This permitted unambiguous localization of a conformational sensitive tryptic split at Arg 198 by N-terminal amino acid sequence analysis. Other splits at Arg 505 and at Arg 819-Lys 825 were insensitive to E1-E2 transitions. Tryptic cleavage of Ca-ATPase after phosphorylation by inorganic phosphate showed that this enzyme form has a conformation similar to that of the vanadate-bound E2 state, both in membranous and in soluble monomeric Ca-ATPase. Hydrophobic labeling of Ca-ATPase in sarcoplasmic reticulum vesicles with the photoactivable reagent trifluoromethyl-[125I]iodophenyl-diazirine indicated that E2 and E2V states are more exposed to the membrane phase than E1 and E1P (Ca2+-occluded) states. The preferential hydrophobic labeling in E2 forms was found to be localized in the A1 tryptic fragment. PMID:2948019

Andersen, J P; Vilsen, B; Collins, J H; Jørgensen, P L

1986-01-01

105

The Substrate-Driven Transition to an Inward-Facing Conformation in the Functional Mechanism of the Dopamine Transporter  

PubMed Central

Background The dopamine transporter (DAT), a member of the neurotransmitter:Na+ symporter (NSS) family, terminates dopaminergic neurotransmission and is a major molecular target for psychostimulants such as cocaine and amphetamine, and for the treatment of attention deficit disorder and depression. The crystal structures of the prokaryotic NSS homolog of DAT, the leucine transporter LeuT, have provided critical structural insights about the occluded and outward-facing conformations visited during the substrate transport, but only limited clues regarding mechanism. To understand the transport mechanism in DAT we have used a homology model based on the LeuT structure in a computational protocol validated previously for LeuT, in which steered molecular dynamics (SMD) simulations guide the substrate along a pathway leading from the extracellular end to the intracellular (cytoplasmic) end. Methodology/Principal Findings Key findings are (1) a second substrate binding site in the extracellular vestibule, and (2) models of the conformational states identified as occluded, doubly occupied, and inward-facing. The transition between these states involve a spatially ordered sequence of interactions between the two substrate-binding sites, followed by rearrangements in structural elements located between the primary binding site and the cytoplasmic end. These rearrangements are facilitated by identified conserved hinge regions and a reorganization of interaction networks that had been identified as gates. Conclusions/Significance Computational simulations supported by information available from experiments in DAT and other NSS transporters have produced a detailed mechanistic proposal for the dynamic changes associated with substrate transport in DAT. This allosteric mechanism is triggered by the binding of substrate in the S2 site in the presence of the substrate in the S1 site. Specific structural elements involved in this mechanism, and their roles in the conformational transitions illuminated here describe, a specific substrate-driven allosteric mechanism that is directly amenable to experiment as shown previously for LeuT.

Shan, Jufang; Javitch, Jonathan A.; Shi, Lei; Weinstein, Harel

2011-01-01

106

Phosphorylation induces a conformational transition near the lipid-water interface of phospholamban reconstituted with the Ca-ATPase.  

PubMed

We have measured conformational changes of phospholamban (PLB) induced both by its interaction with the SR Ca-ATPase and by phosphorylation of Ser-16 by cAMP-dependent protein kinase (PKA) using an engineered PLB having a single cysteine (Cys-24) derivatized with the fluorophore 2-(4'-maleimidylanilino)naphthalene-6-sulfonic acid (ANSmal). This modified mutant PLB is fully functional when co-reconstituted with the affinity-purified Ca-ATPase in liposomes. ANSmal emission properties and its solvent accessibility indicate that Cys-24 is in an aqueous environment outside the membrane. Fluorescence quenching and time-resolved anisotropy measurements of ANSmal-PLB demonstrate distinct structures for PLB in the free and Ca-ATPase-bound state. Both solvent exposure and probe motions of ANSmal are enhanced upon interaction of PLB with the Ca-ATPase. This conformational transition entails conversion of free PLB in a conformation which is insensitive to one which is sensitive to the phosphorylation state of PLB. Upon phosphorylation of Ca-ATPase-bound PLB, a decreased level of solvent exposure of ANSmal is observed, suggesting that the amino acid sequence of PLB near the lipid-water interface acts as a conformational switch in response to the phosphorylation of PLB. A longer correlation time, resolved by anisotropy measurements, corresponding to polypeptide chain fluctuations, is substantially restricted by interaction of PLB with the Ca-ATPase. This restriction is not reversed by phosphorylation of PLB, indicating that the region around Cys-24 near the lipid-water interface does not undergo dissociation from the Ca-ATPase. These results suggest that the phosphorylation by PKA induces a redistribution of PLB-Ca-ATPase protein contacts to relieve the inhibitory effect of PLB for the activation of calcium transport. PMID:12437353

Chen, Baowei; Bigelow, Diana J

2002-11-26

107

Conformational transitions of flexible hydrophobic polyelectrolytes in solutions of monovalent and multivalent salts and their mixtures.  

PubMed

Conformations of cationic polyelectrolytes (PEs), a weak poly(2-vinylpyridine) (P2VP) and a strong poly(N-methyl-2-vinylpyridinium iodide) (qP2VP), adsorbed on mica from saline solutions in the presence of counterions of different valences are studied using in situ atomic force microscopy (AFM). Quantitative characteristics of chain conformations are analyzed using AFM images of the adsorbed molecules. The results of the statistical analysis of the chain contour reveal collapse of the PE coils when ionic strength is in a range from tens to hundreds of millimoles per kilogram and re-expansion of the coils with a further increase of ionic strength up to a region of the saturated saline solutions. The competition between monovalent and multivalent counterions simultaneously present in solutions strongly affects conformations of PE chains even at a very small fraction of multivalent counterions. Shrinkage of PE coils is steeper for multivalent counterions than for monovalent counterions. However, the re-expansion is only incremental in the presence of multivalent counterions. Extended adsorbed coils at low salt concentrations and at very high concentrations of monovalent salt exhibit conformation corresponding to a 2D coil with 0.95 fraction of bound segments (segments in "trains") in the regime of diluted surface concentration of the PE. Shrunken coils in the intermediate range of ionic strength resemble 3D-globules with 0.8 fraction of trains. The incrementally re-expanded PE coils at a high ionic strength remain unchanged at higher multivalent salt concentrations up to the solubility limit of the salt. The formation of a strong PE complex with multivalent counterions at high ionic strength is not well understood yet. A speculative explanation of the observed experimental result is based on possible stabilization of the complex due to hydrophobic interactions of the backbone. PMID:22413781

Trotsenko, Oleksandr; Roiter, Yuri; Minko, Sergiy

2012-03-29

108

Allosteric modulation of the human P-glycoprotein involves conformational changes mimicking catalytic transition intermediates  

Microsoft Academic Search

The drug transport function of human P-glycoprotein (Pgp, ABCB1) can be inhibited by a number of pharmacological agents collectively referred to as modulators or reversing agents. In this study, we demonstrate that certain thioxanthene-based Pgp modulators with an allosteric mode of action induce a distinct conformational change in the cytosolic domain of Pgp, which alters susceptibility to proteolytic digestion. Both

Pratiti Ghosh; Karobi Moitra; Nazli Maki; Saibal Dey

2006-01-01

109

The purple to blue transition of bacteriorhodopsin is accompanied by a loss of the hexagonal lattice and a conformational change  

SciTech Connect

X-ray diffraction measurements show that in contrast to the purple membrane, the bacteriorhodopsin molecules are not organized in a hexagonal lattice in the deionized blue membrane. Addition of Ca{sup 2+} restores both the purple color and the normal (63 {angstrom}) hexagonal protein lattice. In the blue state, the circular dichroism spectrum in the visible has the typical exciton features indicating that a trimeric structure is retained. Time-resolved linear dichrosim measurements show that the blue patch rotates in aqueous suspension with a mean correlation time of 11 ms and provide no evidence for rotational mobility of bacteriorhodopsin within the membrane. The circular dichroism spectra of the blue and the Ca{sup 2+}-regenerated purple state in the far-UV are different, indicating a small change in secondary structure. The thermal stability of the blue membrane is much smaller than that of the purple membrane. At pH 5.0, the irreversible denaturation transition of the blue form has a midpoint at 61{degree}C. The photocycle of the blue membrane ({lambda}{sub ex} 590 nm) has an L intermediate around 540 nm whose decay is slowed down into the millisecond time range (5 ms). Light-dark adaptation in the blue membrane is rapid with an exponential decay time of 38 s at 25{degree}C. The purple to blue transition apparently involves a conformational change in the protein leading to a change in the aggregation state from a highly ordered and stable hexagonal lattice to a disordered array of thermally more labile trimers. The conformational change is of a subtle nature, with only a minor effect on the secondary structure but with a major effect on the opsin shift and the photocycle. It is suggested that the transition involves an equilibrium between two states which is shifted by a change in the surface pH.

Heyn, M.P.; Dudda, C.; Otto, H.; Seiff, F.; Wallat, I. (Freie Universitaet Berlin (Germany, F.R.))

1989-11-14

110

Conformation of ceramide 6 molecules and chain-flip transitions in the lipid matrix of the outermost layer of mammalian skin, the stratum corneum  

NASA Astrophysics Data System (ADS)

Neutron diffraction from oriented multilamellar model stratum corneum (SC) membranes provides information on the internal nanostructure and hydration of the lipid bilayer. The main distinguishing feature of model SC membranes based on ceramide 6 is the extremely small intermembrane space (1 Å). The role of the fully extended (FE) conformation of ceramide 6 molecules in the organization of the nanostructure of the lipid matrix is discussed. The FE conformation gives rise to extremely strong intermembrane attractions (armature reinforcement), which tighten the adjacent bilayers to form steric contacts. Chain-flip transitions in the conformation of ceramide molecules account for structural alterations in native and model SC membranes upon their hydration.

Kiselev, M. A.

2007-05-01

111

Conformation of ceramide 6 molecules and chain-flip transitions in the lipid matrix of the outermost layer of mammalian skin, the stratum corneum  

SciTech Connect

Neutron diffraction from oriented multilamellar model stratum corneum (SC) membranes provides information on the internal nanostructure and hydration of the lipid bilayer. The main distinguishing feature of model SC membranes based on ceramide 6 is the extremely small intermembrane space (1 A). The role of the fully extended (FE) conformation of ceramide 6 molecules in the organization of the nanostructure of the lipid matrix is discussed. The FE conformation gives rise to extremely strong intermembrane attractions (armature reinforcement), which tighten the adjacent bilayers to form steric contacts. Chain-flip transitions in the conformation of ceramide molecules account for structural alterations in native and model SC membranes upon their hydration.

Kiselev, M. A. [Joint Institute for Nuclear Research (Russian Federation)], E-mail: kiselev@jinr.ru

2007-05-15

112

Simulations of CRP:(cAMP)2 in noncrystalline environments show a subunit transition from the open to the closed conformation.  

PubMed Central

The CRP:cAMP complex functions as a transcription factor that facilitates RNA polymerase recognition of several bacterial promoters. Detailed crystal structure information is available for CRP:(cAMP)2 and for CRP:(cAMP)2 complexed with DNA. In the crystalline environment, CRP:(cAMP)2 subunits are asymmetrically related; one subunit has a closed conformation and the other has an open conformation. The CRP:(cAMP)2 complexed with DNA shows both subunits in a closed conformation. We have studied the molecular dynamics of CRP:(cAMP)2 in noncrystalline environments. CRP:(cAMP)2 was simulated for 625 ps in vacuo and for 140 ps in solution. The crystal structure of CRP:(cAMP)2 in the absence of DNA was used as the initial conformation. Molecule optimal dynamic coordinates (MODCs) (García A, 1992, Phys Rev Lett 68:2696) were used to analyze protein conformations sampled during the course of the simulations. Two MODCs define a transition of the open subunit to a closed subunit conformation during the first 125 ps of simulation in vacuo; the resulting subunit conformation is similar to that observed in CRP:(cAMP)2:DNA crystals. Simulation of CRP:(cAMP)2 in solution showed that a transition from the open to the closed state also occurs when water is explicitly included in the calculations. These calculations suggest that the asymmetric conformation of CRP:(cAMP)2 is stabilized by crystal lattice interactions. The predicted solution conformation is more symmetric, with both subunits in a closed conformation.

Garcia, A. E.; Harman, J. G.

1996-01-01

113

Conformation and dynamics of biopharmaceuticals: transition of mass spectrometry-based tools from academe to industry  

PubMed Central

Mass spectrometry plays a very visible role in biopharmaceutical industry, although its use in development, characterization and quality control of protein drugs is mostly limited to the analysis of covalent structure (amino acid sequence and post-translational modifications). Despite the centrality of protein conformation to biological activity, stability and safety of biopharmaceutical products, the expanding arsenal of mass spectrometry-based methods that are currently available to probe higher order structure and conformational dynamics of biopolymers did not enjoy until recently much attention in the industry. This is beginning to change as a result of recent work demonstrating the utility of these experimental tools for various aspects of biopharmaceutical product development and manufacturing. In this work we use a paradigmatic protein drug interferon ?-1a as an example to illustrate the utility of mass spectrometry as a powerful tool not only to assess the integrity of higher order structure of a protein drug, but also to predict consequences of its degradation at a variety of levels.

Kaltashov, Igor A.; Bobst, Cedric E.; Abzalimov, Rinat R.; Berkowitz, Steven A.; Houde, Damian

2009-01-01

114

The 32kDa enamelin undergoes conformational transitions upon calcium binding.  

PubMed

The 32 kDa hydrophilic and acidic enamelin, the most stable cleavage fragment of the enamel specific glycoprotein, is believed to play vital roles in controlling crystal nucleation or growth during enamel biomineralization. Circular dichroism and Fourier transform infrared spectra demonstrate that the secondary structure of the 32 kDa enamelin has a high content of alpha-helix (81.5%). Quantitative analysis on the circular dichroism data revealed that the 32 kDa enamelin undergoes conformational changes with a structural preference to beta-sheet with increasing concentration of calcium ions. We suggest that the increase of beta-sheet conformation in the presence of Ca(2+) may allow preferable interaction of the 32 kDa enamelin with apatite crystal surfaces during enamel biomineralization. The calcium association constant (K(a)=1.55 (+/-0.13)x10(3)M(-1)) of the 32 kDa enamelin calculated from the fitting curve of ellipticity at 222 nm indicated a relatively low affinity. Our current biophysical studies on the 32 kDa enamelin structure provide novel insights towards understanding the enamelin-mineral interaction and subsequently the functions of enamelin during enamel formation. PMID:18508280

Fan, Daming; Lakshminarayanan, Rajamani; Moradian-Oldak, Janet

2008-04-24

115

The 32 kDa Enamelin Undergoes Conformational Transitions upon Calcium Binding  

PubMed Central

The 32 kDa hydrophilic and acidic enamelin, the most stable cleavage fragment of the enamel specific glycoprotein, is believed to play vital roles in controlling crystal nucleation or growth during enamel biomineralization. Circular dichroism and Fourier transform infrared spectra demonstrate that the secondary structure of the 32 kDa enamelin has a high content of ?-helix (81.5%). Quantitative analysis on the circular dichroism data revealed that the 32 kDa enamelin undergoes conformational changes with a structural preference to ?-sheet as a function of calcium ions. We suggest that the increase of ?-sheet conformation upon presence of Ca2+ may allow preferable interaction of the 32 kDa enamelin with apatite crystal surfaces during enamel biomineralization. The calcium association constant of the 32 kDa enamelin calculated from the fitting curve of ellipticity at 222 nm is Ka = 1.55 (±0.13) × 103 M?1, indicating a relatively low affinity. Our current biophysical studies on the 32 kDa enamelin structure provide novel insights towards understanding the enamelin-mineral interaction and subsequently the functions of enamelin during enamel formation.

Fan, Daming; Lakshminarayanan, Rajamani; Moradian-Oldak, Janet

2008-01-01

116

Remarkable solvent-dependent excited-state chirality: a molecular modulator of circularly polarized luminescence.  

PubMed

The photochemical control of ground- and excited-state chirality of (M)-cis-(1) and (P)-trans-(2)-2-nitro-7-(dimethylamino)-9-(2',3'-dihydro-1'H-naphtho[2,1-b]-thiopyran-1'-ylidene)-9H-thioxanthene is described. It is shown that while ground state chirality can be controlled photochemically by irradiation with light of different wavelengths, the excited state chirality can be tuned either photochemically in a similar way or by appropriate choice of solvent. In benzene solution, circularly polarized luminescence of the two isomers with opposite ground-state helicity, (M)-cis-1 and (P)-trans-2, revealed corresponding excited states of opposite helicity. On the contrary, in n-hexane solution, circularly polarized luminescence was identical for the two forms indicating identical excited state chirality. Circularly polarized luminescence (CPL), steady-state and time-dependent fluorescence, and time-resolved microwave conductivity (TRMC) measurements in both n-hexane and benzene are reported, which provide an explanation for the remarkable solvent dependence of excited-state chirality. PMID:14664615

van Delden, Richard A; Huck, Nina P M; Piet, Jacob J; Warman, John M; Meskers, Stefan C J; Dekkers, Harry P J M; Feringa, Ben L

2003-12-17

117

Influence of intermolecular interaction on kinetics of conformational transitions in poly-m-phenyleneisophthalamide  

Microsoft Academic Search

UDC 535.33 It is known that the character and energy of intermolecular interaction (IMI) can appreciably influence the physicomechanical characteristics~ the phase transition temperature, and other properties of the polymers. The role of IMI is especially marked in the solid or in the blocklike state of the polymer. All the polymers can be conditionally divided into three groups according to

P. M. Pakhomov; I. I. Novak; Mo V. Shablygin; V. E. Korsukov

1985-01-01

118

Molecular dynamics simulation of phosphorylation-induced conformational transitions in the mycobacterium tuberculosis response regulator PrrA  

SciTech Connect

Phosphorylation-activated modulation of response regulators (RR) is predominantly used by bacteria as a strategy in regulating their two-component signaling (TCS) systems, the underlying molecular mechanisms are however far from fully understood. In this work we have conducted a molecular dynamics (MD) simulation of the phosphorylation-induced conformational transitions of RRs with the Mycobacterium Tuberculosis PrrA as a particular example. Starting from the full-length inactive structure of PrrA we introduced a local disturbance by phosphorylating the conserved aspartic acid residue, Asp-58, in the regulatory domain. A Go-model-type algorithm packaged with AMBER force fields was then applied to simulate the dynamics upon phosphorylation. The MD simulation shows that the phosphorylation of Asp-58 facilitates PrrA, whose inactive state has a compact conformation with a closed interdomain interface, to open up with its interdomain separation being increased by an average of about 1.5 {angstrom} for a simulation of 20 ns. The trans-activation loop, which is completely buried within the interdomain interface in the inactive PrrA, is found to become more exposed with the phosphorylated structure as well. These results provide more structural details of how the phosphorylation of a local aspartate activates PrrA to undergo a global conformational rearrangement toward its extended active state. This work also indicates that MD simulations can serve as a fast tool to unravel the regulation mechanisms of all RRs, which is especially valuable when the structures of full-length active RRs are currently unavailable.

Chen, Guo [Los Alamos National Laboratory; Mcmahon, Benjamin H [Los Alamos National Laboratory; Tung, Chang - Shung [Los Alamos National Laboratory

2008-01-01

119

MUTATIONS IN SUB-DOMAIN B OF THE MCM HELICASE AFFECT DNA BINDING AND MODULATE CONFORMATIONAL TRANSITIONS  

PubMed Central

Minichromosome maintenance (MCM) proteins are believed to provide the replicative helicase activity in eukaryotes and archaea. The single MCM orthologue from Methanothermobacter thermautotrophicus (MthMCM) has been extensively characterised as a model of the eukaryotic heterohexameric MCM complex. MthMCM forms high molecular weight complexes in solution consistent with a dodecamer. Visualization of this complex by electron microscopy suggests that single and double heptameric or hexameric rings can form. We have mutated two arginine residues (R137, R160) in the N-terminal sub-domain B of MthMCM based on their apparent potential to form inter-ring hydrogen bonds. Both the single R137A and the double RR137,160AA mutants were characterised by a combination of biophysical, biochemical and electron microscopy (EM) techniques. Biophysical analysis coupled with EM studies shows that the R137A mutant forms a double heptameric ring, whereas the RR137,160AA protein assembles as a single heptamer. They both show a defect in DNA binding and a concomitant conformational change in sub-domain A, with the double mutant displaying significant defects in helicase activity as well. We propose a model in which MCM loading and the subsequent activation of the helicase activity involves a conformational transition that is connected to a DNA binding event.

Jenkinson, Elizabeth R.; Costa, Alessandro; Leech, Andrew P.; Patwardhan, Ardan; Onesti, Silvia; Chong, James P.J.

2009-01-01

120

Conformation transitions of blood proteins under influence of physical factors on microwave dielectric method  

NASA Astrophysics Data System (ADS)

In this article, the influence of ?-irradiation and temperature on albumin and fibrinogen conformation and dielectric properties of protein solutions have been studied by the microwave dielectric method. Both the values of the real part ?? (dielectric permittivity) and the imaginary part ?? (dielectric losses) of the complex dielectric permittivity of the aqueous solution of bovine serum albumin and human fibrinogen as functions of temperature and ?-irradiation dose have been obtained. The time of dielectric relaxation of water molecules in the protein solutions was calculated. The hydration of the albumin and fibrinogen molecules was determined. The temperature dependencies of hydration are non-monotonous and have a number of characteristic features at the temperatures 30 34 and 44 47 °C for serum albumin, and 24 and 32 °C for fibrinogen.

Gorobchenko, O. A.; Nikolov, O. T.; Gatash, S. V.

2006-11-01

121

Theoretical modeling of UV-Vis absorption and emission spectra in liquid state systems including vibrational and conformational effects: The vertical transition approximation.  

PubMed

In this paper we describe in detail a general and efficient methodology, based on the perturbed matrix method and molecular dynamics simulations, to model UV-Vis absorption and emission spectra including vibrational and conformational effects. The basic approximation used is to consider all the chromophore atomic coordinates as semiclassical degrees of freedom, hence allowing the calculation of the complete spectral signal by using the electronic vertical transitions as obtained at each possible chromophore configuration, thus including the contributions of vibrations and conformational transitions into the spectrum. As shown for the model system utilized in this paper, solvated 1-phenyl-naphthalene, such an approximation can be rather accurate to reproduce the absorption and emission spectral line shape and properties when, as it often occurs, the vertical vibronic transition largely overlaps the other non-negligible vibronic transitions. PMID:24070274

D'Alessandro, Maira; Aschi, Massimiliano; Mazzuca, Claudia; Palleschi, Antonio; Amadei, Andrea

2013-09-21

122

Theoretical modeling of UV-Vis absorption and emission spectra in liquid state systems including vibrational and conformational effects: The vertical transition approximation  

NASA Astrophysics Data System (ADS)

In this paper we describe in detail a general and efficient methodology, based on the perturbed matrix method and molecular dynamics simulations, to model UV-Vis absorption and emission spectra including vibrational and conformational effects. The basic approximation used is to consider all the chromophore atomic coordinates as semiclassical degrees of freedom, hence allowing the calculation of the complete spectral signal by using the electronic vertical transitions as obtained at each possible chromophore configuration, thus including the contributions of vibrations and conformational transitions into the spectrum. As shown for the model system utilized in this paper, solvated 1-phenyl-naphthalene, such an approximation can be rather accurate to reproduce the absorption and emission spectral line shape and properties when, as it often occurs, the vertical vibronic transition largely overlaps the other non-negligible vibronic transitions.

D'Alessandro, Maira; Aschi, Massimiliano; Mazzuca, Claudia; Palleschi, Antonio; Amadei, Andrea

2013-09-01

123

B-Z transition of (dA-T)n duplexes induced by a spermine porphyrin-conjugate via an intermediate DNA conformation.  

PubMed

The spermine conjugate of the cationic porphyrin ligand () selectively induced the B-Z transition of the [(dA-T)n]2 sequence at low salt concentrations. The [(dG-C)n]2 sequence was not transformed into the Z-form. The B-Z transition was induced via an intermediate DNA conformation, which was formed by the external binding and formation of an assembly of onto B-DNA. PMID:23979223

Sasaki, Hideaki; Sasaki, Shigeki

2013-09-10

124

pH-dependent conformational transitions in conalbumin (ovotransferrin), a metalloproteinase from hen egg white.  

PubMed

Acid unfolding pathway of conalbumin (CA), a monomeric glycoprotein from hen egg white, has been investigated using far- and near-UV CD spectroscopy, intrinsic fluorescence emission, extrinsic fluorescence probe 1-anilino-8-napthalene sulfonate (ANS) and dynamic light scattering (DLS). We observe pH-dependent changes in secondary and tertiary structure of CA. It has native-like ?-helical secondary structure at pH 4.0 but loss structure at pH 3.0. The CA existed exclusively as a pre-molten globule state and molten globule state in solution at pH 4.0 and pH 3.0, respectively. The effect of pH on the conformation and thermostability of CA points toward its heat resistance at neutral pH. DLS results show that MG state existed as compact form in aqueous solutions with hydrodynamic radii of 4.7 nm. Quenching of tryptophan fluorescence by acrylamide further confirmed the accumulation of an intermediate state, partly unfolded, in-between native and unfolded states. PMID:21833676

Rabbani, Gulam; Ahmad, Ejaz; Zaidi, Nida; Khan, Rizwan Hasan

2011-12-01

125

Intrinsic Free Energy of the Conformational Transition of the KcsA Signature Peptide from Conducting to Nonconducting State  

PubMed Central

We explore a conformational transition of the TATTVGYG signature peptide of the KcsA ion selectivity filter and its GYG to AYA mutant from the conducting ?-strand state into the nonconducting pII-like state using a novel technique for multidimensional optimization of transition path ensembles and free energy calculations. We find that the wild type peptide, unlike the mutant, intrinsically favors the conducting state due to G77 backbone propensities and additional hydrophobic interaction between the V76 and Y78 side chains in water. The molecular mechanical free energy profiles in explicit water are in very good agreement with the corresponding adiabatic energies from the Generalized Born Molecular Volume (GBMV) implicit solvent model. However comparisons of the energies to higher level B3LYP/6–31G(d) Density Functional Theory calculations with Polarizable Continuum Model (PCM) suggest that the nonconducting state might be more favorable than predicted by molecular mechanics simulations. By extrapolating the single peptide results to the tetrameric channel, we propose a novel hypothesis for the ion selectivity mechanism.

Khavrutskii, Ilja V.; Fajer, Mikolai; McCammon, J. Andrew

2010-01-01

126

An Infrared Spectroscopic Study of the Conformational Transition of Elastin-Like Polypeptides  

PubMed Central

The infrared spectroscopy of elastin-like polypeptides and the relation to the inverse thermal transition are discussed. To correlate the spectroscopic observations with structure a density function theory model was created that captures the essential hydrogen bonding and packing of the ?-spiral structure proposed for elastin and elastin-like polypeptides. The infrared spectrum was calculated using periodic boundary conditions and a method for estimating the difference dipole moment permits both frequencies and intensities to be obtained for the modeling of spectra. The two observed amide I bands at 1615 cm?1 and 1656 cm?1 are shown to arise from the ?-spiral structure. The increase in intensity of these bands with increasing salt concentration and temperature is assigned to the closer association of strands of the ?-spiral. The sharp inverse temperature transition is observed within 1°C and involves a change in secondary structure that involves formation of interstrand ?-sheets for ?25% of the amino acids. This conclusion is consistent with available data and simulations that have been reported to date.

Serrano, Vesna; Liu, Wenge; Franzen, Stefan

2007-01-01

127

Janus-like squaramide-based hosts: dual mode of binding and conformational transitions driven by ion-pair recognition.  

PubMed

New tripodal squaramide-based hosts have been synthesised and structurally characterised by spectroscopic methods. In 2.5?% (v/v) [D(6)]DMSO in CDCl(3), compound 4 formed dimeric assemblies [log?K(dim)=3.68(8)] as demonstrated by (1)H?NMR spectroscopy and UV dilution experiments. AFM and SEM analyses revealed the formation of a network of bundled fibres, which indicates a preferential mechanism for aggregation. These C(3)-symmetric tripodal hosts exhibited two different and mutually exclusive modes of binding, each one easily accessible by simultaneous reorientation of the squaramide groups. In the first, a convergent disposition of the NH squaramide protons allowed the formation of an array of N-H???X(-) hydrogen bonds with anions. In the second mode, reorientation of carbonyl squaramide groups allowed multiple C=O???H interactions with ammonium cations. The titration of 4 with different tetraalkylammonium iodides persistently showed the formation of 1:1 complexes, as well as 1:2 and 1:3 complexes. The corresponding stoichiometries and binding affinities of the complexes were evaluated by multi-regression analysis. The formation of high-order complexes, supported by ROESY, NOESY and mass spectrometry experiments, has been attributed to the insertion of NR(4)I ion pairs between the carbonyl and NH protons of the squaramide groups located in adjacent arms of 4. The observed effects reflect the induction of significant conformational changes in the hosts, mainly in relation to the relative orientation of the squaramide groups adapting their geometries to incoming ion-pair complementary substrates. The results presented herein identify and fully describe two different modes of ion-pair recognition aimed at directing conformational transitions in the host, therefore establishing a base for controlling more elaborate movements of molecular devices through ion-pair recognition. PMID:22532395

Soberats, Bartomeu; Martínez, Luis; Sanna, Elena; Sampedro, Angel; Rotger, Carmen; Costa, Antoni

2012-04-24

128

Conformational Transitions Underlying Pore Opening and Desensitization in Membrane-embedded Gloeobacter violaceus Ligand-gated Ion Channel (GLIC)  

PubMed Central

Direct structural insight into the mechanisms underlying activation and desensitization remain unavailable for the pentameric ligand-gated channel family. Here, we report the structural rearrangements underlying gating transitions in membrane-embedded GLIC, a prokaryotic homologue, using site-directed spin labeling and electron paramagnetic resonance (EPR) spectroscopy. We particularly probed the conformation of pore-lining second transmembrane segment (M2) under conditions that favor the closed and the ligand-bound desensitized states. The spin label mobility, intersubunit spin-spin proximity, and the solvent-accessibility parameters in the two states clearly delineate the underlying protein motions within M2. Our results show that during activation the extracellular hydrophobic region undergoes major changes involving an outward translational movement, away from the pore axis, leading to an increase in the pore diameter, whereas the lower end of M2 remains relatively immobile. Most notably, during desensitization, the intervening polar residues in the middle of M2 move closer to form a solvent-occluded barrier and thereby reveal the location of a distinct desensitization gate. In comparison with the crystal structure of GLIC, the structural dynamics of the channel in a membrane environment suggest a more loosely packed conformation with water-accessible intrasubunit vestibules penetrating from the extracellular end all the way to the middle of M2 in the closed state. These regions have been implicated to play a major role in alcohol and drug modulation. Overall, these findings represent a key step toward understanding the fundamentals of gating mechanisms in this class of channels.

Velisetty, Phanindra; Chalamalasetti, Sreevatsa V.; Chakrapani, Sudha

2012-01-01

129

Tyr66 acts as a conformational switch in the closed-to-open transition of the SHP-2 N-SH2-domain phosphotyrosine-peptide binding cleft  

PubMed Central

Background The N-terminal SH2 domain (N-SH2) of the non-receptor tyrosine phosphatase SHP-2 is involved both in localization of SHP-2 by recognition of phosphotyrosine (pY) peptides and self-inhibition of SHP-2 phosphatase activity through the formation of a protein – protein interface with the phosphatase domain. Mutations that disrupt this interface break the coupling between pY-peptide binding cleft conformation and self-inhibition, thereby increasing both SHP-2 phosphatase activity and pY-peptide binding affinity, and are associated with the congenital condition Noonan syndrome and various pediatric leukemias. To better characterize the molecular process involved in N-SH2 pY-dependent binding, we have applied explicit-solvent molecular dynamics simulations to study the closed-to-open transition of the N-SH2 pY-peptide binding cleft. Results The existence of stable conformations in the left-handed helical and the extended regions of Tyr66 ?/? space prevent rapid interconversion of the backbone and create a conformational switch such that Tyr66 in a left-handed helical backbone conformation results in an open cleft and in an extended backbone conformation results in a closed cleft. The stable conformations arise from deep, well-localized free-energy minima in the left-handed helical and extended regions of the Tyr66 ?/? map. Changing the Tyr66 backbone conformation from extended to left-handed helical induces a closed-to-open transition in the cleft, and the reverse change in backbone conformation induces the reverse, open-to-closed transition. In the open-cleft state, weak solvent-exposed interactions involving the sidechains of Tyr66, Asp40, Lys55, and Gln57 serve to anchor the Tyr66 sidechain to the surface of the protein and away from the binding cleft entrance, thereby facilitating pY-peptide access to the binding cleft. Conclusion The simulations point to a regulatory role for Tyr66 and surrounding residues in SHP-2 function: mutations at Tyr66, Asp40, Lys55, and/or Gln57 are predicted to break the switching mechanism and negatively impact pY-peptide binding. This in turn would interfere with cellular localization and the coupled SHP-2 phosphatase activity. The structurally well-defined binding cleft conformations resulting from the switch-like transition suggest the possibility of applying structure-based methods to develop inhibitors of N-SH2 pY-peptide binding to serve as research tools for signal transduction and precursors to therapeutics for SHP-2-related diseases.

Guvench, Olgun; Qu, Cheng-Kui; MacKerell, Alexander D

2007-01-01

130

Coarse-grained simulations of transitions in the E2-to-E1 conformations for Ca ATPase (SERCA) show entropy-enthalpy compensation.  

PubMed

SERCA is a membrane transport protein that has been extensively studied. There are a large number of highly resolved X-ray structures and several hundred mutations that have been characterized functionally. Despite this, the molecular details of the catalytic cycle, a cycle that includes large conformational changes, is not fully understood. In this computational study, we provide molecular dynamics descriptions of conformational changes during the E2?E1 transitions. The motivating point for these calculations was a series of insertion mutants in the A-M3 linker region that led to significant shifts in measured rates between the E2 and E1 states, as shown by experimental characterization. Using coarse-grained dynamic importance sampling within the context of a population shift framework, we sample on the intermediates along the transition pathway to address the mechanism for the conformational changes and the effects of the insertion mutations on the kinetics of the transition. The calculations define an approximation for the relative changes in entropy and enthalpy along the transition. These are found to be important for understanding the experimentally observed differences in rates. In particular, the interactions between cytoplasmic domains, water interactions, and the shifts in protein degrees of freedom with the insertion mutations show mutual compensation for the E2?E1 transitions in wild-type and mutant systems. PMID:22684148

Nagarajan, Anu; Andersen, Jens Peter; Woolf, Thomas B

2012-06-07

131

Conformational transitions of poly(dA-dC).poly(dG-dT) induced by high salt or in ethanolic solution.  

PubMed Central

Poly(dA-dC).poly(dG-dT) was studied by circular dichroism in the presence of high CsCl concentrations and in ethanolic solutions. This alternating purine-pyrimidine duplex may undergo two conformational transitions from a B-type to a novel structure and subsequently into an A-form. Cs+ ions or increasing ethanol concentrations induced a change of the B-type CD spectrum and an inversion of the long wavelength CD band. Lowering the temperature below 0 C or addition of small amounts of Ca++ ions were particularly potent in producing a large negative CD band. A modified B-type structure or a conversion into a left-handed Z-form is considered for this conformational transition.

Zimmer, C; Tymen, S; Marck, C; Guschlbauer, W

1982-01-01

132

Structural and conformational changes concomitant with the E1–E2 transition in H +K +ATPase: a comparative protein modeling study  

Microsoft Academic Search

Comparative modeling studies on conserved regions of the gastric H+K+-ATPase reveal that the E1–E2 conformational transition induces significant tertiary structural changes while conserving the secondary structure. The residues 516–530 of the cytoplasmic domain and TM10 within the transmembrane (TM) regions undergo maximum tertiary structural changes. The luminal regions exhibit comparatively lesser tertiary structural deviations. Residues 249–304 show maximum secondary structural

P. Hima Bindu; G. Madhavi Sastry; U. Suryanarayana Murty; G. Narahari Sastry

2004-01-01

133

Structural change in the Brill transition of Nylon m\\/ n (2) conformational disordering as viewed from the temperature-dependent infrared spectral measurements  

Microsoft Academic Search

The structural changes in the Brill transition of aliphatic Nylons m\\/n have been investigated by carrying out the temperature-dependent infrared spectral measurement for Nylon 6\\/10 –[–NH–(CH2)6–NHCO–(CH2)8–CO–]n–, Nylon 6\\/12 –[–NH–(CH2)6–NHCO–(CH2)10–CO–]n– and Nylon 10\\/10 –[–NH–(CH2)10–NHCO–(CH2)8–CO–]n–. They took the crystal structure of ?-form at room temperature. By heating the samples up to the Brill transition temperature region, the conformation of the methylene segments

Yayoi Yoshioka; Kohji Tashiro; Chellaswami Ramesh

2003-01-01

134

Retinoic acid biosynthesis catalyzed by retinal dehydrogenases relies on a rate-limiting conformational transition associated with substrate recognition.  

PubMed

Retinoic acid (RA), a metabolite of vitamin A, exerts pleiotropic effects throughout life in vertebrate organisms. Thus, RA action must be tightly regulated through the coordinated action of biosynthetic and degrading enzymes. The last step of retinoic acid biosynthesis is irreversibly catalyzed by the NAD-dependent retinal dehydrogenases (RALDH), which are members of the aldehyde dehydrogenase (ALDH) superfamily. Low intracellular retinal concentrations imply efficient substrate molecular recognition to ensure high affinity and specificity of RALDHs for retinal. This study addresses the molecular basis of retinal recognition in human ALDH1A1 (or RALDH1) and rat ALDH1A2 (or RALDH2), through the comparison of the catalytic behavior of retinal analogs and use of the fluorescence properties of retinol. We show that, in contrast to long chain unsaturated substrates, the rate-limiting step of retinal oxidation by RALDHs is associated with acylation. Use of the fluorescence resonance energy transfer upon retinol interaction with RALDHs provides evidence that retinal recognition occurs in two steps: binding into the substrate access channel, and a slower structural reorganization with a rate constant of the same magnitude as the kcat for retinal oxidation: 0.18 vs. 0.07 and 0.25 vs. 0.1 s(-1) for ALDH1A1 and ALDH1A2, respectively. This suggests that the conformational transition of the RALDH-retinal complex significantly contributes to the rate-limiting step that controls the kinetics of retinal oxidation, as a prerequisite for the formation of a catalytically competent Michaelis complex. This conclusion is consistent with the general notion that structural flexibility within the active site of ALDH enzymes has been shown to be an integral component of catalysis. PMID:23220587

Bchini, Raphaël; Vasiliou, Vasilis; Branlant, Guy; Talfournier, François; Rahuel-Clermont, Sophie

2012-12-07

135

Solvent dependence of ultrafast ground state recovery of the triphenylmethane dyes, brilliant green and malachite green  

NASA Astrophysics Data System (ADS)

We have studied femtosecond ground state recovery dynamics of the triphenylmethane dyes brilliant green (BG) and malachite green (MG) by pump-probe spectroscopy at the center wavelength of 635 nm with a time resolution of 33 fs. The ultrafast recovery of the ground state bleach was highly nonexponential and depended on the solvent viscosity, although all time constants were shorter than the solvation times obtained from other measurements. We observed a plateau or a rise component in the signal, which indicates an intermediate state. The rise time showed a viscosity dependence, even in the ultrafast time domain. It should be noted that the decay times were always longer for BG than MG, while the rise time did not show a solute dependence. The torsional motion of the amino-substituted phenyl group may be involved in the ultrafast process to the intermediate state, but lack of a solute dependence indicates that only a small conformational change is involved.

Nagasawa, Yutaka; Ando, Yoshito; Okada, Tadashi

1999-10-01

136

Solvent-dependent stabilization of metastable monolayer polymorphs at the liquid-solid interface.  

PubMed

Self-assembly of 1,3,5-tris(4'-biphenyl-4"-carbonitrile)benzene monolayers was studied at the liquid-solid interface by scanning tunneling microscopy. Application of different fatty acid homologues as solvents revealed a solvent-induced polymorphism. Yet, tempering triggered irreversible phase transitions of the initially self-assembled monolayers, thereby indicating their metastability. Interestingly, in either case, the same thermodynamically more stable and more densely packed monolayer polymorph was obtained after thermal treatment, irrespective of the initial structure. Again, the same densely packed structure was obtained in complementary solvent-free experiments conducted under ultrahigh vacuum conditions. Thus, self-assembly of metastable polymorphs at room temperature is explained by adsorption of partially solvated species under kinetic control. The irreversible phase transitions are induced by thermal desolvation, that is, desorption of coadsorbed solvent molecules. PMID:23875955

Sirtl, Thomas; Song, Wentao; Eder, Georg; Neogi, Subhadip; Schmittel, Michael; Heckl, Wolfgang M; Lackinger, Markus

2013-07-29

137

Insights into the potential functionality of single-chain force-induced conformational transitions in polymer networks: implications for polysaccharide signaling in the plant cell wall.  

PubMed

The behavior of biopolymer networks comprised of clickable polysaccharide chains that can undergo force-induced conformational transitions was investigated during straining using a simulation technique. The simulation was carried out both using an affine deformation field and alternatively using Lees-Edwards boundary conditions as an example of a nonaffine case. In the affine situation the simulated stress-strain curves were found to be consistent with results obtained by evaluating the molecular force-extension curve at a single average extension and calculating the bulk modulus as an average over all possible orientations with respect to the deformation. While in all cases examined the macroscopic mechanical responses of networks of randomly oriented chains, consisting either of simple extensible wormlike chains or their clickable analogs, were found to be indistinguishable, the simulation additionally allowed the number of chains containing sugar rings in different conformational states to be monitored, and this was found to change significantly during straining. This supports the hypothesis that in networks of randomly oriented clickable polysaccharide chains, such conformational transitions could have biological significance as stress switches in signaling processes but that they are unlikely to affect the bulk rheological properties of tissue. PMID:21230520

Schuster, E; Lundin, L; Williams, M A K

2010-11-22

138

Lattice Monte Carlo study of pre-conformal dynamics in strongly flavoured QCD in the light of the chiral phase transition at finite temperature  

NASA Astrophysics Data System (ADS)

We study the thermal phase transition in colour SU(Nc=3) Quantum Chromodynamics (QCD) with a variable number of fermions in the fundamental representation by using lattice Monte Carlo simulations. We collect the (pseudo) critical couplings ?Lc for Nf=(0,4,6, and 8), and we investigate the pre-conformal dynamics associated with the infra-red fixed point in terms of the Nf dependence of the transition temperature. We propose three independent estimates of the number of flavour Nf* where the conformal phase would emerge, which give consistent results within the largish errors. We consider lines of fixed Nt in the space of (Nf, bare lattice coupling), and locate the vanishing of the step-scaling function for Nf*˜11.1±1.6. We define a typical interaction strength gTc at the scale of critical temperature Tc and we find that gTc meets the zero temperature critical couplings estimated by the two-loop Schwinger-Dyson equation or the IRFP coupling in the four-loop beta-function at Nf*˜12.5±1.6. Further, we study the Nf dependences of Tc/M where M is a UV Nf independent reference scale determined by utilising the coupling at the scale of the lattice spacing. Then, Tc/M turns out to be a decreasing function of Nf and the vanishing Tc/M indicates the emergence of the conformal window at Nf*˜10.4±1.2.

Miura, Kohtaroh; Lombardo, Maria Paola

2013-06-01

139

Initiation of the 3':5'-AMP-induced protein kinase A I? regulatory subunit conformational transition. Part I. A202 and A326 are critical residues.  

PubMed

Protein-ligand docking and molecular dynamics studies have shown that the key event initiated by 3':5'-AMP binding to the A- and B-domains of protein kinase A I? regulatory subunit is formation of a hydrogen bond between 3':5'-AMP and A202(A326) (the residue in parentheses being from the B-domain). The A202(A326) amide group movement associated with the bond formation leads to reorganization of the phosphate binding cassette (PBC) (the short 3(10)-helix becomes the long ?-helix). This process results in L203(L327) displacement and finally causes hinge (B-helix) rotation. The L203(L327) displacement and packing into the hydrophobic pocket formed by the PBC and ?2?3-loop also depends on the ?2?3-loop conformation. The correct conformation is maintained by R, I, E, but not K at position 209(333) of the A- and B-domains. So, the R209K and R333K mutants have problems with reaching B-conformation. The apo-form of the 3':5'-AMP-binding domain also undergoes transition from H- to B-conformation. In this case, the movement of A202(A326) amide group seems to be a result of reorganization of the PBC into a more stable ?-helix. PMID:22813586

Rogacheva, O N; Shchegolev, B F; Stefanov, V E; Zakharov, G A; Savvateeva-Popova, E V

2012-05-01

140

Initiation of the 3':5'-AMP-induced protein kinase A I? regulatory subunit conformational transition. Part II. Inhibition by Rp-3':5'-AMPS.  

PubMed

Protein-ligand docking and ab initio calculations have shown that the 3':5'-AMP phosphorothioate analog (Rp-3':5'-AMPS) blocks the A326 amide group displacement typical of transition from the H- to B-conformation within the B-domain of protein kinase A I? R-subunit. This behavior of Rp-3':5'-AMPS leads to the inhibition of initial stages of hydrophobic relay operation. In accordance with the proposed hypothesis, Rp-3':5'-AMPS similarly to 3':5'-AMP forms a hydrogen bond with the amide group of A326; however, the properties of this bond together with the position of the sulfur atom prevent the movement of A326. Finally, the Rp-3':5'-AMPS-bound domain appears to be locked in the H-conformation, which is in agreement with the X-ray data. PMID:22813587

Rogacheva, O N; Shchegolev, B F; Stefanov, V E; Savvateeva-Popova, E V

2012-05-01

141

Analyzing the robustness of the MM/PBSA free energy calculation method: application to DNA conformational transitions.  

PubMed

The ability to predict and characterize free energy differences associated with conformational equilibria or the binding of biomolecules is vital to understanding the molecular basis of many important biological functions. As biological studies focus on larger molecular complexes and properties of the genome, proteome, and interactome, the development and characterization of efficient methods for calculating free energy becomes increasingly essential. The aim of this study is to examine the robustness of the end-point free energy method termed the molecular mechanics Poisson-Boltzmann solvent accessible surface area (MM/PBSA) method. Specifically, applications of MM/PBSA to the conformational equilibria of nucleic acid (NA) systems are explored. This is achieved by comparing A to B form DNA conformational free energy differences calculated using MM/PBSA with corresponding free energy differences determined with a more rigorous and time-consuming umbrella sampling algorithm. In addition, the robustness of NA MM/PBSA calculations is also evaluated in terms of the sensitivity towards the choice of force field and the choice of solvent model used during conformational sampling. MM/PBSA calculations of the free energy difference between A-form and B-form DNA are shown to be in very close agreement with the PMF result determined using an umbrella sampling approach. Further, it is found that the MM/PBSA conformational free energy differences were also in agreement using either the CHARMM or AMBER force field. The influence of ionic strength on conformational stability was particularly insensitive to the choice of force field. Finally, it is also shown that the use of a generalized Born implicit solvent during conformational sampling results in free energy estimates that deviate slightly from those obtained using explicitly solvated MD simulations in these NA systems. PMID:21284003

Brice, Allyn R; Dominy, Brian N

2011-02-01

142

Atomic details of near-transition state conformers for enzyme phosphoryl transfer revealed by MgF3- rather than by phosphoranes  

PubMed Central

Prior evidence supporting the direct observation of phosphorane intermediates in enzymatic phosphoryl transfer reactions was based on the interpretation of electron density corresponding to trigonal species bridging the donor and acceptor atoms. Close examination of the crystalline state of ?-phosphoglucomutase, the archetypal phosphorane intermediate-containing enzyme, reveals that the trigonal species is not PO3-, but is MgF3- (trifluoromagnesate). Although MgF3- complexes are transition state analogues rather than phosphoryl group transfer reaction intermediates, the presence of fluorine nuclei in near-transition state conformations offers new opportunities to explore the nature of the interactions, in particular the independent measures of local electrostatic and hydrogen-bonding distributions using F19 NMR. Measurements on three ?-PGM-MgF3--sugar phosphate complexes show a remarkable relationship between NMR chemical shifts, primary isotope shifts, NOEs, cross hydrogen bond F?H-N scalar couplings, and the atomic positions determined from the high-resolution crystal structure of the ?-PGM-MgF3--G6P complex. The measurements provide independent validation of the structural and isoelectronic MgF3- model of near-transition state conformations.

Baxter, Nicola J.; Bowler, Matthew W.; Alizadeh, Tooba; Cliff, Matthew J.; Hounslow, Andrea M.; Wu, Bin; Berkowitz, David B.; Williams, Nicholas H.; Blackburn, G. Michael; Waltho, Jonathan P.

2010-01-01

143

Conformational transitions regulate the exposure of a DNA-binding domain in the RuvBL1-RuvBL2 complex  

PubMed Central

RuvBL1 and RuvBL2, also known as Pontin and Reptin, are AAA+ proteins essential in small nucleolar ribonucloprotein biogenesis, chromatin remodelling, nonsense-mediated messenger RNA decay and telomerase assembly, among other functions. They are homologous to prokaryotic RuvB, forming single- and double-hexameric rings; however, a DNA binding domain II (DII) is inserted within the AAA+ core. Despite their biological significance, questions remain regarding their structure. Here, we report cryo-electron microscopy structures of human double-ring RuvBL1–RuvBL2 complexes at ?15 Å resolution. Significantly, we resolve two coexisting conformations, compact and stretched, by image classification techniques. Movements in DII domains drive these conformational transitions, extending the complex and regulating the exposure of DNA binding regions. DII domains connect with the AAA+ core and bind nucleic acids, suggesting that these conformational changes could impact the regulation of RuvBL1–RuvBL2 containing complexes. These findings resolve some of the controversies in the structure of RuvBL1–RuvBL2 by revealing a mechanism that extends the complex by adjustments in DII.

Lopez-Perrote, Andres; Munoz-Hernandez, Hugo; Gil, David; Llorca, Oscar

2012-01-01

144

The Conformational Transitions of Uncharged Poly-L-Lysine. Alpha Helix-Random Coil-beta Structure.  

National Technical Information Service (NTIS)

The heat-induced transition of poly-L-lysine, alpha helix-random coil-beta form, was studied, mainly by optical rotatory dispersion (ORD). Below T-beta the transition has the properties of a reversible alpha-helix-random coil equilibrium. Above T-beta, th...

B. Davidson G. D. Fasman

1967-01-01

145

Conformational changes of chicken liver bile acid-binding protein bound to anionic lipid membrane are coupled to the lipid phase transitions.  

PubMed

Chicken liver bile acid-binding protein (L-BABP) binds to anionic lipid membranes by electrostatic interactions and acquires a partly folded state [Nolan, V., Perduca, M., Monaco, H., Maggio, B. and Montich, G. G. (2003) Biochim. Biophys. Acta 1611, 98-106]. We studied the infrared amide I' band of L-BABP bound to dipalmitoylphosphatidylglycerol (DPPG), dimyristoylphosphatidylglycerol (DMPG) and palmitoyloleoylphosphatidylglycerol (POPG) in the range of 7 to 60 degrees C. Besides, the thermotrophic behaviour of DPPG and DMPG was studied in the absence and in the presence of bound-protein by differential scanning calorimetry (DSC) and infrared spectra of the stretching vibration of methylene and carbonyl groups. When L-BABP was bound to lipid membranes in the liquid-crystalline state (POPG between 7 and 30 degrees C) acquired a more unfolded conformation that in membranes in the gel state (DPPG between 7 and 30 degrees C). Nevertheless, this conformational change of the protein in DMPG did not occur at the temperature of the lipid gel to liquid-crystalline phase transition detected by infrared spectroscopy. Instead, the degree of unfolding in the protein was coincident with a phase transition in DMPG that occurs with heat absorption and without change in the lipid order. PMID:17466937

Decca, María Belén; Perduca, Massimiliano; Monaco, Hugo L; Montich, Guillermo G

2007-03-28

146

Conformational transitions of flanking purines in HIV-1 RNA dimerization initiation site kissing complexes studied by CHARMM explicit solvent molecular dynamics.  

PubMed

Dimerization of HIV-1 genomic RNA is initiated by kissing loop interactions at the Dimerization Initiation Site (DIS). Dynamics of purines that flank the 5' ends of the loop-loop helix in HIV-1 DIS kissing complex were explored using explicit solvent molecular dynamics (MD) simulations with the CHARMM force field. Multiple MD simulations (200 ns in total) of X-ray structures for HIV-1 DIS Subtypes A, B, and F revealed conformational variability of flanking purines. In particular, the flanking purines, which in the starting X-ray structures are bulged-out and stack in pairs, formed a consecutive stack of four bulged-out adenines at the beginning of several simulations. This conformation is seen in the crystal structure of DIS Subtype F with no interference from crystal packing, and was frequently reported in our preceding MD studies performed with the AMBER force field. However, as CHARMM simulations progressed, the four continuously stacked adenines showed conformational transitions from the bulged-out into the bulged-in geometries. Although such an arrangement has not been seen in any X-ray structure, it has been suggested by a recent NMR investigation. In CHARMM simulations, in the longer time scale, the flanking purines display the tendency to move to bulged-in conformations. This is in contrast with the AMBER simulations, which indicate a modest prevalence for bulged-out flanking base positions in line with the X-ray data. The simulations also suggest that the intermolecular stacking between purines from the opposite hairpins can additionally stabilize the kissing complex. PMID:18412127

Sarzy?ska, Joanna; Réblová, Kamila; Sponer, Jirí; Kuli?ski, Tadeusz

2008-09-01

147

A conformational transition in the structure of a 2'-thiomethyl-modified DNA visualized at high resolution.  

PubMed

Crystal structures of A-form and B-form DNA duplexes containing 2'-S-methyl-uridines reveal that the modified residues adopt a RNA-like C3'-endo pucker, illustrating that the replacement of electronegative oxygen at the 2'-carbon of RNA by sulfur does not appear to fundamentally alter the conformational preference of the sugar in the oligonucleotide context and sterics trump stereoelectronics. PMID:19333476

Pallan, Pradeep S; Prakash, Thazha P; Li, Feng; Eoff, Robert L; Manoharan, Muthiah; Egli, Martin

2009-02-26

148

A conformational transition in the structure of a 2'-thiomethyl-modified DNA visualized at high resolution  

SciTech Connect

Crystal structures of A-form and B-form DNA duplexes containing 2'-S-methyl-uridines reveal that the modified residues adopt a RNA-like C3'-endo pucker, illustrating that the replacement of electronegative oxygen at the 2'-carbon of RNA by sulfur does not appear to fundamentally alter the conformational preference of the sugar in the oligonucleotide context and sterics trump stereoelectronics.

Pallan, Pradeep S.; Prakash, Thazha P.; Li, Feng; Eoff, Robert L.; Manoharan, Muthiah; Egli, Martin; (Isis Pharm.); (Alnylam Pharm.); (Vanderbilt)

2009-06-17

149

Conformational transitions of the sarcoplasmic reticulum Ca-ATPase studied by time-resolved EPR and quenched-flow kinetics.  

PubMed

We have used time-resolved electron paramagnetic resonance (EPR) and quenched-flow kinetics in order to investigate the dynamics of Ca-ATPase conformational changes involved in Ca2+ pumping in sarcoplasmic reticulum (SR) membranes at 2 degrees C. The Ca-ATPase was selectively labeled with an iodoacetamide spin label (IASL), which yields EPR spectra sensitive to enzyme conformational changes during ATP induced enzymatic cycling. The addition of ATP, AMPPCP, CrATP, or ADP decreased the rotational mobility of a fraction of the probes, indicating a distinct protein conformational state corresponding to this probe population, while Pi under conditions producing "backdoor" phosphorylation produced no spectral change. Transient changes in the amplitude of the restricted component associated with the pre-steady state of Ca2+ pumping were detected with 10 ms time resolution after an [ATP] jump produced by laser flash photolysis of caged ATP in the EPR sample. The laser energy was adjusted to generate 100 microM ATP from 1 mM caged ATP. At 0.1 M KCl, the EPR transient consisted of a brief initial lag phase, a monoexponential phase with a rate of 20 s-1, and a decay back to the initial intensity after the ATP had been consumed. Raising [KCl] from 0.1 to 0.4 M slowed the rate of the exponential phase from 20 to 6 s-1. Lowering the pH from 7 to 6, which increased the rate of caged ATP photolysis, eliminated the lag but did not change the apparent rate of the EPR signal rise. Parallel acid quenched-flow experiments conducted at 0.1 M KCl and 100 microM ATP produced fast (50-58 s-1) and slow (20 s-1) phases of phosphoenzyme formation. Increasing [KCl] from 0.1 to 0.4 M decreased the rate of the slow phase of phosphorylation from 20 to 5 s-1, without affecting the fast phase. The close correlation between the slow phase of phosphorylation and the exponential phase of the EPR signal suggests that the spin probe monitors a conformational event associated with phosphoenzyme formation in a population of catalytic sites with delayed kinetics. We propose that this constraint is imposed by conformational coupling between the catalytic subunits in a Ca-ATPase oligomer and that, consequently, the EPR signal reflects changes in quaternary protein structure as well as changes in secondary and tertiary structure associated with ATP-dependent phosphorylation. PMID:7718593

Mahaney, J E; Froehlich, J P; Thomas, D D

1995-04-11

150

Nonequilibrium phase transitions and a nonequilibrium critical point from anti-de Sitter space and conformal field theory correspondence.  

PubMed

We find novel phase transitions and critical phenomena that occur only outside the linear-response regime of current-driven nonequilibrium states. We consider the strongly interacting (3+1)-dimensional N = 4 large-N(c) SU(N(c)) supersymmetric Yang-Mills theory with a single flavor of fundamental N = 2 hypermultiplet as a microscopic theory. We compute its nonlinear nonballistic quark-charge conductivity by using the AdS/CFT correspondence. We find that the system exhibits a novel nonequilibrium first-order phase transition where the conductivity jumps and the sign of the differential conductivity flips at finite current density. A nonequilibrium critical point is discovered at the end point of the first-order regime. We propose a nonequilibrium steady-state analogue of thermodynamic potential in terms of the gravity-dual theory in order to define the transition point. Nonequilibrium analogues of critical exponents are proposed as well. The critical behavior of the conductivity is numerically confirmed on the basis of these proposals. The present work provides a new example of nonequilibrium phase transitions and nonequilibrium critical points. PMID:23005930

Nakamura, Shin

2012-09-18

151

Conformational Transitions in Viroids and Virusoids: Comparison of Results from Energy Minimization Algorithm and from Experimental Data  

Microsoft Academic Search

Viroids are single-stranded circular RNA molecules of 240 to 400 nucleotides which are pathogens of certain higher plants and replicate autonomously in the host cell. Virusoids are similar to viroids in respect to size and circularity but replicate only as genomic part of a plant virus. Their structure and structural transitions have been investigated by thermodynamic, kinetic and hydrodynamic methods.

G. Sieger; H. Hofmann; J. Förtsch; H. J. Gross; J. W. Randies; H. L. Sänger; D. Riesner

1984-01-01

152

Temperature-induced conformational transition of intestinal fatty acid binding protein enhancing ligand binding: a functional, spectroscopic, and molecular modeling study.  

PubMed

Intestinal fatty acid binding protein (IFABP) undergoes a reversible thermal transition between 35 and 50 degreesC, as revealed by circular dichroism spectroscopy in the near-UV region. For the apoprotein, the molar ellipticity measured at 254 nm (possibly implicating the environment around F17 and/or F55) decreases significantly in this temperature range, while in the holoprotein (bound to oleic acid), this phenomenon is not observed. Concomitantly, an increase in the activity of binding to [14C]oleic acid occurs. Nevertheless, other spectroscopic evidence indicates that the beta-barrel structure, the major motif of this protein, is highly stable up to 70 degreesC. No changes associated with conformation were detected for both structures by fourth-derivative analysis of the UV absorption spectra, circular dichroism in the far-UV region, and intrinsic fluorescence measurements. Further structural information arises from experiments in which binding to the anionic fluorescent probes 1-anilinonaphthalene-8-sulfonic acid (ANS) and its dimer bisANS was examined. The fluorescence intensity of bound ANS diminishes monotonically, whereas that of bisANS increases slightly in the temperature range of 35-50 degreesC. Given the different size of these probes, model building suggests that ANS would be able to sense regions located deeply inside the cavity, while bisANS could also reach the vicinity of the small helical domain of this protein. In light of these results, we believe that this subtle conformational transition of IFABP, which positively influences the binding activity, would involve fluctuations at the peripheral "entry portal" region for the ligand. This interpretation is compatible with the discrete disorder observed in this place in apo-IFABP, as evidenced by NMR spectroscopy [Hodsdon, M. E., and Cistola, D. P. (1997) Biochemistry 36, 1450-1460]. PMID:9843451

Arighi, C N; Rossi, J P; Delfino, J M

1998-11-24

153

Time-resolved infrared absorption studies of the solvent-dependent vibrational relaxation dynamics of chlorine dioxide  

NASA Astrophysics Data System (ADS)

We report a series of time-resolved infrared absorption studies on chlorine dioxide (OClO) dissolved in H2O, D2O, and acetonitrile. Following the photoexcitation at 401 nm, the evolution in optical density for frequencies corresponding to asymmetric stretch of OClO is measured with a time resolution of 120+/-50 fs. The experimentally determined optical-density evolution is compared with theoretical models of OClO vibrational relaxation derived from collisional models as well as classical molecular-dynamics (MD) studies. The vibrational relaxation rates in D2O are reduced by a factor of 3 relative to H2O consistent with the predictions of MD. This difference reflects modification of the frequency-dependent solvent-solute coupling accompanying isotopic substitution of the solvent. Also, the geminate-recombination quantum yield for the primary photofragments resulting in the reformation of ground-state OClO is reduced in D2O relative to H2O. It is proposed that this reduction reflects enhancement of the dissociation rate accompanying vibrational excitation along the asymmetric-stretch coordinate. In contrast to H2O and D2O, the vibrational-relaxation dynamics in acetonitrile are not well described by the theoretical models. Reproduction of the optical-density evolution in acetonitrile requires significant modification of the frequency-dependent solvent-solute coupling derived from MD. It is proposed that this modification reflects vibrational-energy transfer from the asymmetric stretch of OClO to the methyl rock of acetonitrile. In total, the results presented here provide a detailed description of the solvent-dependent geminate-recombination and vibrational-relaxation dynamics of OClO in solution.

Bolinger, Joshua C.; Bixby, Teresa J.; Reid, Philip J.

2005-08-01

154

pH- and thermal-dependent conformational transition of PGAIPG, a repeated hexapeptide sequence from tropoelastin.  

PubMed

The secondary structure of PGAIPG (Pro-Gly-Ala-IIe-Pro-Gly), a repeated hexapeptide of tropoelastin, in buffer solution of different pH was determined by using attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopy. The thermal-dependent structural change of PGAIPG in aqueous solution or in solid state was also examined by thermal FTIR microspectroscopy. The conformation of PGAIPG in aqueous solution exhibited a pH-dependent structural characterization. A predominant peak at 1614 cm(-1) (aggregated beta-sheet) with a shoulder near 1560 cm(-1) (beta-sheet) appeared in pH 5.5-8.5 buffer solutions. A new broad shoulder at 1651 cm(-1) (random coil and/or alpha-helix) with 1614 cm(-1) was observed in the pH 4.5 buffer solution. However, the broad shoulder at 1651 cm(-1) was converted to a maximum peak at 1679 cm(-1) (beta-turn/antiparallel beta-sheet) when the pH shifted from 4.5 to 3.5, but the original pronounced peak at 1614 cm(-1) became a shoulder. Once the pH was lowered to 2.5, the IR spectrum of PGAIPG was dominated by major absorption at 1679 cm(-1) with a minor peak at 1552 cm(-1) (alpha-helix/random coil). The result indicates that the pH was a predominant factor to transform PGAIPG structure from aggregated beta-sheet (pH 8.5) to beta-turn/intermolecular antiparallel beta-sheet (pH 2.5). Moreover, a partial conformation of PGAIPG with minor alpha-helix/random coil structures was also explored in the lower pH buffer solution. There was no thermal-dependent structural change for solid-state PGAIPG. The thermal-induced formation of aggregated beta-sheet for PGAIPG in aqueous solution was found from 28 to 30 degrees C, however, which might be correlated with the formation of an opaque gel that turned from clear solution. The formation of aggregated beta-sheet structure for PGAIPG beyond 30 degrees C might be due to the intermolecular hydrogen bonded interaction between the hydrophobic PGAIPG fragments induced by coacervation. PMID:15752567

Lin, Shan-Yang; Hsieh, Tzu-Feng; Wei, Yen-Shan

2005-04-01

155

Dynamic conformational transitions of the EGF receptor in living mammalian cells determined by FRET and fluorescence lifetime imaging microscopy.  

PubMed

We have revealed a reorientation of ectodomain I of the epidermal growth factor receptor (EGFR; ErbB1; Her1) in living CHO cells expressing the receptor, upon binding of the native ligand EGF. The state of the unliganded, nonactivated EGFR was compared to that exhibited after ligand addition in the presence of a kinase inhibitor that prevents endocytosis but does not interfere with binding or the ensuing conformational rearrangements. To perform these experiments, we constructed a transgene EGFR with an acyl carrier protein sequence between the signal peptide and the EGFR mature protein sequence. This protein, which behaves similarly to wild-type EGFR with respect to EGF binding, activation, and internalization, can be labeled at a specific serine in the acyl carrier tag with a fluorophore incorporated into a 4'-phosphopantetheine (P-pant) conjugate transferred enzymatically from the corresponding CoA derivative. By measuring Förster resonance energy transfer between a molecule of Atto390 covalently attached to EGFR in this manner and a novel lipid probe NR12S distributed exclusively in the outer leaflet of the plasma membrane, we determined the apparent relative separation of ectodomain I from the membrane under nonactivating and activating conditions. The data indicate that the unliganded domain I of the EGFR receptor is situated much closer to the membrane before EGF addition, supporting the model of a self-inhibited configuration of the inactive receptor in quiescent cells. PMID:23839800

Ziomkiewicz, Iwona; Loman, Anastasia; Klement, Reinhard; Fritsch, Cornelia; Klymchenko, Andrey S; Bunt, Gertrude; Jovin, Thomas M; Arndt-Jovin, Donna J

2013-07-09

156

Exploration of conformational transition in the aryl-binding site of human FXa using molecular dynamics simulations.  

PubMed

Human coagulation Factor X (FX), a member of the vitamin K-dependent serine protease family, is a crucial component of the human coagulation cascade. Activated FX (FXa) participates in forming the prothrombinase complex on activated platelets to convert prothrombin to thrombin in coagulation reactions. In the current study, 30-ns MD simulations were performed on both the open and closed states of human FXa. Root mean squares (RMS) fluctuations showed that structural fluctuations concentrated on the loop regions of FXa, and the presence of a ligand in the closed system resulted in larger fluctuations of the gating residues. The open system had a gating distance from 9.23 to 11.33 Å, i.e., significantly larger than that of the closed system (4.69-6.35 Å), which allows diversified substrates of variable size to enter. Although the solvent accessible surface areas (SASA) of FXa remained the same in both systems, the open system generally had a larger total SASA or hydrophobic SASA (or both) for residues surrounding the S4 pocket. Additionally, more hydrogen bonds were formed in the closed state than in the open state of FXa, which is believed to play a significant role in maintaining the closed confirmation of the aryl-binding site. Based on the results of MD simulations, we propose that an induced-fit mechanism governs the functioning of human coagulation FX, which helps provide a better understanding of the interactions between FXa and its substrate, and the mechanism of the conformational changes involved in human coagulation. PMID:22116613

Wang, Jing-Fang; Hao, Pei; Li, Yi-Xue; Dai, Jian-Liang; Li, Xuan

2011-11-25

157

Distinct Roles of the Active-site Mg2+ Ligands, Asp882 and Asp705, of DNA Polymerase I (Klenow Fragment) during the Prechemistry Conformational Transitions*  

PubMed Central

DNA polymerases catalyze the incorporation of deoxynucleoside triphosphates into a growing DNA chain using a pair of Mg2+ ions, coordinated at the active site by two invariant aspartates, whose removal by mutation typically reduces the polymerase activity to barely detectable levels. Using two stopped-flow fluorescence assays that we developed previously, we have investigated the role of the carboxylate ligands, Asp705 and Asp882, of DNA polymerase I (Klenow fragment) in the early prechemistry steps that prepare the active site for catalysis. We find that neither carboxylate is required for an early conformational transition, reported by a 2-aminopurine probe, that takes place in the open ternary complex after binding of the complementary dNTP. However, the subsequent fingers-closing step requires Asp882; this step converts the open ternary complex into the closed conformation, creating the active-site geometry required for catalysis. Crystal structures indicate that the Asp882 position changes very little during fingers-closing; this side chain may therefore serve as an anchor point to receive the dNTP-associated metal ion as the nucleotide is delivered into the active site. The Asp705 carboxylate is not required until after the fingers-closing step, and we suggest that its role is to facilitate the entry of the second Mg2+ into the active site. The two early prechemistry steps that we have studied take place normally at very low Mg2+ concentrations, although higher concentrations are needed for covalent nucleotide addition, consistent with the second metal ion entering the ternary complex after fingers-closing.

Bermek, Oya; Grindley, Nigel D. F.; Joyce, Catherine M.

2011-01-01

158

First- and second-row transition metal oxa-aza macrocyclic complexes: a DFT study of an octahedral conformation.  

PubMed

A theoretical study of structures of the 1,7,1 l,17-tetraoxa-2,6,12,16-tetraaza-cycloeicosane ligand ([20]AneN(4)O(4)) coordinated to Fe(2+), Co(2+), Ni(2+), Ru(2+), Rh(2+), and Pd(2+) transition metals ions was carried out with the DFT/B3LYP method. Complexes were fully optimized in C(s) symmetry with the metal ions coordinated either to nitrogen (1a) or oxygen atoms (1b). For all the cases performed in this work, 1a was always more stable than 1b. Considering each row it is possible to see that the binding energy increases with the atomic number. The M(2+) cation binding energies increase in the following order: Fe(2+)

Lima, Francisco C A; Viana, Rommel B; da Silva, Thais T; Wardell, Solange M S V; do Filho, Armando P Nascimento; Carneiro, José Walkimar M; Comar, Moacyr; da Silva, Albérico B F

2012-01-15

159

Analytical model and multiscale simulations of A? peptide aggregation in lipid membranes: towards a unifying description of conformational transitions, oligomerization and membrane damage.  

PubMed

The mechanisms underlying the formation of extracellular amyloid plaques on neuronal membranes, a major hallmark of Alzheimer's disease, are the subject of intense debate. Here we use multiscale simulations and analytical theory to unveil the early steps of the spontaneous self-assembly of membrane-embedded ?-helical A? (1-40) peptides. Based on a simple analytical model describing the electrostatic repulsions among water-exposed charged residues, the presence of distorted structures called "frustrated helices" is predicted. Large scale (20 ?s) Coarse Grained simulations of 36 replicas of A? (1-40) performed within a POPC lipid matrix confirmed the formation of supramolecular assemblies which resemble a twisted ribbon. Fully atomistic simulations have demonstrated the stability of these helical structures. Concomitant to the formation of these large assemblies, CG simulations evidenced membrane curvature and substantiate the view that these assemblies may entail mechanical stress on membrane structure. We think that these findings provide an alternative view to the traditional models that consider a conformational transition towards ?-sheet rich structures as a prerequisite for triggering membrane damage and, eventually, neurotoxicity. PMID:23588697

Pannuzzo, Martina; Milardi, Danilo; Raudino, Antonio; Karttunen, Mikko; La Rosa, Carmelo

2013-04-15

160

Conformational studies on parathion  

NASA Astrophysics Data System (ADS)

Theoretical conformational studies have been carried out at the density functional theory (DFT) level on parathion (O,O-diethyl-O-p-nitrophenyl phosphorothioate), to correlate the conformational properties of this molecule with its biological activity. Different conformers of parathion have been taken into account, and the accuracy of our theoretical approach has been gauged against the results of the second-order Møller-Plesset perturbation calculations. The aqueous solvation of these molecules has been studied at the DFT level, using a polarized continuum model (PCM) with a conductor-like screening reaction field approach. The results show that parathion has high conformational flexibility in the gas phase, as well as in an aqueous medium, and the barriers to transition to different low-energy conformers are thermally allowed. The molecular electrostatic potential surfaces of the various low-energy conformers of this molecule have been compared with the related non-aged enzyme-bound organophosphorus structure to investigate the role of the calculated conformers on the biological activity of this molecule.

Ford-Green, Jason; Majumdar, D.; Leszczynski, Jerzy

161

Solvent dependent competition between fluorescence resonance energy transfer and through bond energy transfer in rhodamine appended hexaphenylbenzene derivatives for sensing of Hg(2+) ions.  

PubMed

Hexaphenylbenzene (HPB) derivatives 5 and 7 having rhodamine B moieties have been designed and synthesized, and have been shown to display solvent dependent. Fluorescence resonance energy transfer (FRET) and through bond energy transfer (TBET) in the presence of Hg(2+) ions among the various cations (Cu(2+), Pb(2+), Zn(2+), Ni(2+), Cd(2+), Ag(+), Ba(2+), Mg(2+), K(+), Na(+), and Li(+)) have been tested. Derivative 5 displays quite high through bond energy transfer efficiency in the presence of Hg(2+) ions in methanol whereas derivative 7 exhibits better FRET efficiency in the presence of Hg(2+) ions in THF and CH(3)CN than derivative 5. PMID:23385981

Bhalla, Vandana; Vij, Varun; Tejpal, Ruchi; Singh, Gopal; Kumar, Manoj

2013-04-01

162

Effect of donor-acceptor orientation on solvent-dependent three-photon activity in through-space charge-transfer systems - case study of [2,2]-paracyclophane derivatives.  

PubMed

We study the effect of donor-acceptor orientation on solvent-dependent three-photon transition probabilities (?(3PA)) of representative through-space charge-transfer (TSCT) systems, namely, doubly positively charged [2,2]-paracyclophane derivatives. Our cubic response calculations reveal that the value of ?(3PA) may be as high as 10(6) a.u., which can further be increased by a specific orientation of the donor-acceptor moieties. To explain the origin of the solvent cum orientation dependency of ?(3PA), we have calculated different three-photon tensor components using a two-state model, noting that only a few tensor elements contribute significantly to the overall ?(3PA) value. We show that this dependence is due to the large dipole moment difference between the ground and excited states of the systems. The dominance of a few tensor elements indicates a synergistic involvement of ?-conjugation and TSCT in the large ?(3PA) of these systems. PMID:24036953

Alam, Md Mehboob; Chattopadhyaya, Mausumi; Chakrabarti, Swapan; Ruud, Kenneth

2013-09-25

163

Molecular conformational stability in cyclotrimethylene trinitramine crystals.  

PubMed

The cyclotrimethylene trinitramine (RDX) molecule has four conformations denoted as Caaa, Caae, Caee, and Ceee, of which Caae is the conformer stabilized at room temperature in the ?-RDX crystal subjected to atmospheric pressure. The barriers for transition between these conformers are evaluated using a molecular model both in vacuum and in the crystal. Apart from Caae, the only conformer stabilized in ?-RDX is Caee and this occurs when the crystal is strained. The concentration of Caee depends on strain and temperature. The conformers interact elastically and electrostatically, which leads to their spatial clustering. Furthermore, the transition between Caae and Caee is a stochastic process characterized by temporal correlations. This is an effect of the field-mediated spatial interaction of conformers. It is observed that fluctuations in the intra-molecular effective temperature correlate with conformation transitions. The effect is quantified for both Caae-Caee and Caee-Caae transitions. PMID:21766960

Mathew, N; Picu, R C

2011-07-14

164

Mechanistic Studies of Ce(IV)-Mediated Oxidation of ?-Dicarbonyls: Solvent-Dependent Behavior of Radical Cation Intermediates  

PubMed Central

The Ce(IV) initiated oxidation of synthetically relevant ?-diketones and ?-keto silyl enol ethers were explored in three solvents: acetonitrile, methylene chloride, and methanol. The studies presented herein show that the rate of reaction between Ce(IV) and the substrates is dependent upon the polarity of the solvent. Thermochemical studies and analysis are interpreted to be consistent with transition state stabilization by solvent being primarily responsible for the rate of substrate oxidation. Kinetic investigation of radical cations obtained from oxidations of ?-diketones reveal that a more ordered transition state for the radical cation decay is achieved through the direct involvement of methanol in the deprotonation of the intermediate. In the case of radical cations derived from ?-keto silyl enol ethers, experimental data supports a mechanism involving unimolecular decay of the intermediate. Remarkably, radical cations derived from ?-diketones and ?-keto silyl enol ethers are surprisingly stable in methylene chloride.

Jiao, Jingliang; Zhang, Yang; Devery, James J.; Xu, Luna; Deng, Jennifer; Flowers, Robert A.

2008-01-01

165

Solvent dependent frequency shift and Raman noncoincidence effect of Sdbnd O stretching mode of Dimethyl sulfoxide in liquid binary mixtures  

NASA Astrophysics Data System (ADS)

The isotropic and anisotropic Raman peak frequencies of Sdbnd O stretching mode of Dimethyl sulfoxide (DMSO) have been discussed in different chemical and isotopic solvent molecules using different mechanisms. The shifting of peak frequency in further dilution of DMSO with solvent molecule is observed for all solvents. Transition dipole - transition dipole interaction and hydrogen bonding may play a major role in shifting of peak frequencies. The non-coincidence effect (NCE) of DMSO was determined for all the solvents and compared with four theoretical models such as McHale's model, Mirone's modification of McHale's model, Logan's model and Onsager-Fröhlich dielectric continuum model respectively. Most of the theoretical models are largely consistent with our experimental data.

Upadhyay, Ganesh; Devi, Th. Gomti; Singh, Ranjan K.; Singh, A.; Alapati, P. R.

2013-05-01

166

Slow Conformational Changes in MutS and DNA Direct Ordered Transitions between Mismatch Search, Recognition and Signaling of DNA Repair.  

PubMed

MutS functions in mismatch repair (MMR) to scan DNA for errors, identify a target site and trigger subsequent events in the pathway leading to error removal and DNA re-synthesis. These actions, enabled by the ATPase activity of MutS, are now beginning to be analyzed from the perspective of the protein itself. This study provides the first ensemble transient kinetic data on MutS conformational dynamics as it works with DNA and ATP in MMR. Using a combination of fluorescence probes (on Thermus aquaticus MutS and DNA) and signals (intensity, anisotropy and resonance energy transfer), we have monitored the timing of key conformational changes in MutS that are coupled to mismatch binding and recognition, ATP binding and hydrolysis, as well as sliding clamp formation and signaling of repair. Significant findings include (a) a slow step that follows weak initial interaction between MutS and DNA, in which concerted conformational changes in both macromolecules control mismatch recognition, and (b) rapid, binary switching of MutS conformations that is concerted with ATP binding and hydrolysis and (c) is stalled after mismatch recognition to control formation of the ATP-bound MutS sliding clamp. These rate-limiting pre- and post-mismatch recognition events outline the mechanism of action of MutS on DNA during initiation of MMR. PMID:23973435

Sharma, Anushi; Doucette, Christopher; Biro, F Noah; Hingorani, Manju M

2013-08-20

167

Conformational transitions of the phosphodiester backbone in native DNA: two-dimensional magic-angle-spinning 31P-NMR of DNA fibers.  

PubMed Central

Solid-state 31P-NMR is used to investigate the orientation of the phosphodiester backbone in NaDNA-, LiDNA-, MgDNA-, and NaDNA-netropsin fibers. The results for A- and B-DNA agree with previous interpretations. We verify that the binding of netropsin to NaDNA stabilizes the B form, and find that in NaDNA, most of the phosphate groups adopt a conformation typical of the A form, although there are minor components with phosphate orientations close to the B form. For LiDNA and MgDNA samples, on the other hand, we find phosphate conformations that are in variance with previous models. These samples display x-ray diffraction patterns that correspond to C-DNA. However, we find two distinct phosphate orientations in these samples, one resembling that in B-DNA, and one displaying a twist of the PO4 groups about the O3-P-O4 bisectors. The latter conformation is not in accordance with previous models of C-DNA structure. Images FIGURE 2 FIGURE 3 FIGURE 6 FIGURE 7 FIGURE 8 FIGURE 9 FIGURE 10 FIGURE 14

Song, Z; Antzutkin, O N; Lee, Y K; Shekar, S C; Rupprecht, A; Levitt, M H

1997-01-01

168

Conformable seal  

DOEpatents

Sealing apparatus and method, comprising first and second surfaces or membranes, at least one of which surfaces is deformable, placed in proximity to one another. Urging means cause these surfaces to contact one another in a manner such that the deformable surface deforms to conform to the geometry of the other surface, thereby creating a seal. The seal is capable of undergoing multiple cycles of sealing and unsealing.

Neef, W.S.; Lambert, D.R.

1982-08-10

169

A quantitative measure for protein conformational heterogeneity  

NASA Astrophysics Data System (ADS)

Conformational heterogeneity is a defining characteristic of proteins. Intrinsically disordered proteins (IDPs) and denatured state ensembles are extreme manifestations of this heterogeneity. Inferences regarding globule versus coil formation can be drawn from analysis of polymeric properties such as average size, shape, and density fluctuations. Here we introduce a new parameter to quantify the degree of conformational heterogeneity within an ensemble to complement polymeric descriptors. The design of this parameter is guided by the need to distinguish between systems that couple their unfolding-folding transitions with coil-to-globule transitions and those systems that undergo coil-to-globule transitions with no evidence of acquiring a homogeneous ensemble of conformations upon collapse. The approach is as follows: Each conformation in an ensemble is converted into a conformational vector where the elements are inter-residue distances. Similarity between pairs of conformations is quantified using the projection between the corresponding conformational vectors. An ensemble of conformations yields a distribution of pairwise projections, which is converted into a distribution of pairwise conformational dissimilarities. The first moment of this dissimilarity distribution is normalized against the first moment of the distribution obtained by comparing conformations from the ensemble of interest to conformations drawn from a Flory random coil model. The latter sets an upper bound on conformational heterogeneity thus ensuring that the proposed measure for intra-ensemble heterogeneity is properly calibrated and can be used to compare ensembles for different sequences and across different temperatures. The new measure of conformational heterogeneity will be useful in quantitative studies of coupled folding and binding of IDPs and in de novo sequence design efforts that are geared toward controlling the degree of heterogeneity in unbound forms of IDPs.

Lyle, Nicholas; Das, Rahul K.; Pappu, Rohit V.

2013-09-01

170

Conformational stability of apoflavodoxin.  

PubMed

Flavodoxins are alpha/beta proteins that mediate electron transfer reactions. The conformational stability of apoflavodoxin from Anaboena PCC 7119 has been studied by calorimetry and urea denaturation as a function of pH and ionic strength. At pH > 12, the protein is unfolded. Between pH 11 and pH 6, the apoprotein is folded properly as judged from near-ultraviolet (UV) circular dichroism (CD) and high-field 1H NMR spectra. In this pH interval, apoflavodoxin is a monomer and its unfolding by urea or temperature follows a simple two-state mechanism. The specific heat capacity of unfolding for this native conformation is unusually low. Near its isoelectric point (3.9), the protein is highly insoluble. At lower pH values (pH 3.5-2.0), apoflavodoxin adopts a conformation with the properties of a molten globule. Although apoflavodoxin at pH 2 unfolds cooperatively with urea in a reversible fashion and the fluorescence and far-UV CD unfolding curves coincide, the transition midpoint depends on the concentration of protein, ruling out a simple two-state process at acidic pH. Apoflavodoxin constitutes a promising system for the analysis of the stability and folding of alpha/beta proteins and for the study of the interaction between apoflavoproteins and their corresponding redox cofactors. PMID:8819170

Genzor, C G; Beldarraín, A; Gómez-Moreno, C; López-Lacomba, J L; Cortijo, M; Sancho, J

1996-07-01

171

Combined Use of Residual Dipolar Couplings and Solution X-ray Scattering To Rapidly Probe Rigid-Body Conformational Transitions in a Non-phosphorylatable Active-Site Mutant of the 128 kDa Enzyme I Dimer  

SciTech Connect

The first component of the bacterial phosphotransferase system, enzyme I (EI), is a multidomain 128 kDa dimer that undergoes large rigid-body conformational transitions during the course of its catalytic cycle. Here we investigate the solution structure of a non-phosphorylatable active-site mutant in which the active-site histidine is substituted by glutamine. We show that perturbations in the relative orientations and positions of the domains and subdomains can be rapidly and reliably determined by conjoined rigid-body/torsion angle/Cartesian simulated annealing calculations driven by orientational restraints from residual dipolar couplings and shape and translation information afforded by small- and wide-angle X-ray scattering. Although histidine and glutamine are isosteric, the conformational space available to a Gln side chain is larger than that for the imidazole ring of His. An additional hydrogen bond between the side chain of Gln189 located on the EIN{sup {alpha}/{beta}} subdomain and an aspartate (Asp129) on the EIN{sup {alpha}} subdomain results in a small ({approx}9{sup o}) reorientation of the EIN{sup {alpha}} and EIN{sup {alpha}/{beta}} subdomains that is in turn propagated to a larger reorientation ({approx}26{sup o}) of the EIN domain relative to the EIC dimerization domain, illustrating the positional sensitivity of the EIN domain and its constituent subdomains to small structural perturbations.

Takayama, Yuki; Schwieters, Charles D.; Grishaev, Alexander; Ghirlando, Rodolfo; Clore, G. Marius (NIH)

2012-10-23

172

Twisting of the second transmembrane alpha-helix of the mitochondrial ADP/ATP carrier during the transition between two carrier conformational states.  

PubMed

To investigate the structural and functional features of the second alpha-helical transmembrane segment (TM2) of the mitochondrial ADP/ATP carrier (AAC), we adopted cysteine scanning mutagenesis analysis. Single-cysteine mutations of yeast AAC were systematically introduced at residues 98-106 in TM2, and the mutants were treated with the fluorescent SH reagent eosin-5-maleimide (EMA). EMA modified different amino acid residues of alpha-helical TM2 between the two distinct carrier conformations, called the m-state and the c-state, in which the substrate recognition site faces the matrix and cytosol, respectively. When amino acids in the helix were projected on a wheel plot, these EMA-modified amino acids were observed at distinct sides of the wheel. Since the SH reagent specifically modified cysteine in the water-accessible environment, these results indicate that distinct helical surfaces of TM2 faced the water-accessible space between the two conformations, possibly as a result of twisting of this helix. In the recently reported crystal structure of bovine AAC, several amino acids faced cocrystallized carboxyatractyloside (CATR), a specific inhibitor of the carrier. These residues correspond to those modified with EMA in the yeast carrier in the c-state. Since the binding site of CATR is known to overlap that of the transport substrate, the water-accessible space was thought to be a substrate transport pathway, and hence, the observed twisting of TM2 between the m-state and the c-state may be involved in the process of substrate translocation. On the basis of the results, the roles of TM2 in the transport function of AAC were discussed. PMID:15568812

Kihira, Yoshitaka; Iwahashi, Akihiro; Majima, Eiji; Terada, Hiroshi; Shinohara, Yasuo

2004-12-01

173

GlcNAc-Thiazoline conformations.  

PubMed

The title compound, a powerful inhibitor of retaining N-acetylhexosaminidases, can move freely among three pyranose solution conformations of similar energy-two twist boats and the (4)C(1) chair-as revealed by NMR, calculational, and crystallographic studies. It binds in the enzyme active site only in the pseudo-(4)C(1) conformation, however, in which it most closely resembles the hypothetical bound substrate transition state, a (4)E sofa that is approximately trigonal bipyramidal at the anomeric carbon. PMID:19223181

Knapp, Spencer; Fash, David; Abdo, Mohannad; Emge, Thomas J; Rablen, Paul R

2009-02-03

174

Viscoelasticity, Conformational Transition and Ultrastructure of Kappa-Carrageenan in the Presence of Potassium Ion around the Critical Total Ion Concentration  

NASA Astrophysics Data System (ADS)

Rheology, microDSC, and confocal laser scanning microscopy were used to study the effect of potassium ion on the viscoelastic behavior, disorder-order transition and the ultrastructure, respectively, of kappa-carrageenan in aqueous medium in the vicinity of the critical total ionic concentration (C*). The rheological tests showed a ``weak'' gel behavior, with G'>G'' and both moduli dependent on frequency. However, during heating, microDSC showed two zones: one attributed to the presence of ordered double helices without aggregation, and another to the fusion of aggregated double helices. Microscopy showed a three-dimensional network whose continuity depends of the concentration of added potassium ions. For a gel to be formed, a sufficient amount of potassium ion is necessary to promote complete aggregation of double helices so they can form a continuous three-dimensional network.

Núñez-Santiago, María C.; Tecante, Alberto; Durand, Sylvie; Garnier, Catherine; Doublier, Jean L.

2008-07-01

175

Crystal Structures of Progressive Ca2+ Binding States of the Ca2+ Sensor Ca2+ Binding Domain 1 (CBD1) from the CALX Na+/Ca2+ Exchanger Reveal Incremental Conformational Transitions*  

PubMed Central

Na+/Ca2+ exchangers (NCX) constitute a major Ca2+ export system that facilitates the re-establishment of cytosolic Ca2+ levels in many tissues. Ca2+ interactions at its Ca2+ binding domains (CBD1 and CBD2) are essential for the allosteric regulation of Na+/Ca2+ exchange activity. The structure of the Ca2+-bound form of CBD1, the primary Ca2+ sensor from canine NCX1, but not the Ca2+-free form, has been reported, although the molecular mechanism of Ca2+ regulation remains unclear. Here, we report crystal structures for three distinct Ca2+ binding states of CBD1 from CALX, a Na+/Ca2+ exchanger found in Drosophila sensory neurons. The fully Ca2+-bound CALX-CBD1 structure shows that four Ca2+ atoms bind at identical Ca2+ binding sites as those found in NCX1 and that the partial Ca2+ occupancy and apoform structures exhibit progressive conformational transitions, indicating incremental regulation of CALX exchange by successive Ca2+ binding at CBD1. The structures also predict that the primary Ca2+ pair plays the main role in triggering functional conformational changes. Confirming this prediction, mutagenesis of Glu455, which coordinates the primary Ca2+ pair, produces dramatic reductions of the regulatory Ca2+ affinity for exchange current, whereas mutagenesis of Glu520, which coordinates the secondary Ca2+ pair, has much smaller effects. Furthermore, our structures indicate that Ca2+ binding only enhances the stability of the Ca2+ binding site of CBD1 near the hinge region while the overall structure of CBD1 remains largely unaffected, implying that the Ca2+ regulatory function of CBD1, and possibly that for the entire NCX family, is mediated through domain interactions between CBD1 and the adjacent CBD2 at this hinge.

Wu, Mousheng; Le, Hoa Dinh; Wang, Meitian; Yurkov, Vladimir; Omelchenko, Alexander; Hnatowich, Mark; Nix, Jay; Hryshko, Larry V.; Zheng, Lei

2010-01-01

176

Native-state conformational dynamics of GART: A regulatory pH-dependent coil-helix transition examined by electrostatic calculations  

PubMed Central

Glycinamide ribonucleotide transformylase (GART) undergoes a pH-dependent coil–helix transition with pKa ? 7. An ?-helix is formed at high pH spanning 8 residues of a 21-residue-long loop, comprising the segment Thr120–His121–Arg122–Gln123–Ala124–Leu125–Glu126–Asn127. To understand the electrostatic nature of this loop–helix, called the activation loop–helix, which leads to the formation and stability of the ?-helix, pKa values of all ionizable residues of GART have been calculated, using Poisson–Boltzmann electrostatic calculations and crystallographic data. Crystallographic structures of high and low pH E70A GART have been used in our analysis. Low pKa values of 5.3, 5.3, 3.9, 1.7, and 4.7 have been calculated for five functionally important histidines, His108, His119, His121, His132, and His137, respectively, using the high pH E70A GART structure. Ten theoretical single and double mutants of the high pH E70A structure have been constructed to idey pairwise interactions of ionizable residues, which have aided in elucidating the multiplicity of electrostatic interactions of the activation loop–helix, and the impact of the activation helix on the catalytic site. Based on our pKa calculations and structural data, we propose that: (1) His121 forms a molecular switch for the coil–helix transition of the activation helix, depending on its protonation state; (2) a strong electrostatic interaction between His132 and His121 is observed, which can be of stabilizing or destabilizing nature for the activation helix, depending on the relative orientation and protonation states of the rings of His121 and His132; (3) electrostatic interactions involving His119 and Arg122 play a role in the stability of the activation helix; and (4) the activation helix contains the helix-promoting sequence Arg122–Gln123–Ala124–Leu125–Glu126, but its alignment relative to the N and C termini of the helix is not optimal, and is possibly of a destabilizing nature. Finally, we provide electrostatic evidence that the formation and closure of the activation helix create a hydrophobic environment for catalytic-site residue His108, to facilitate catalysis.

Morikis, Dimitrios; Elcock, Adrian H.; Jennings, Patricia A.; McCammon, J. Andrew

2001-01-01

177

A toxic monomeric conformer of the polyglutamine protein  

Microsoft Academic Search

Polyglutamine (polyQ) diseases are classified as conformational neurodegenerative diseases, like Alzheimer and Parkinson diseases, and they are caused by proteins with an abnormally expanded polyQ stretch. However, conformational changes of the expanded polyQ protein and the toxic conformers formed during aggregation have remained poorly understood despite their important role in pathogenesis. Here we show that a ?-sheet conformational transition of

Takashi Inui; H Akiko Popiel; Nobuhiro Fujikake; Kazuhiro Hasegawa; Yoshihiro Urade; Yuji Goto; Hironobu Naiki; Yoshitaka Nagai; Tatsushi Toda

2007-01-01

178

Conformations, structural transitions and visible near-infrared absorption spectra of four-, five- and six-coordinated Cu(II) aqua complexes.  

PubMed

We have performed Car-Parrinello molecular dynamics simulations at ambient conditions for four-, five- and six-coordinated Cu(II) aqua complexes. The molecular geometry has been investigated in terms of Cu-O, Cu-H bond lengths and O-Cu-O bond angles and compared with earlier experimental measurement results and theoretical calculations. We find that the average Cu-O and Cu-H bond lengths increase with increasing coordination number. We have also observed relatively faster structural transition in the case of five-coordinated complex between trigonal bipyramidal and square pyramidal geometry. This result deviates from the findings of the earlier report (A. Pasquarello et al., Science, 2001, 291, 856) on copper(II) in aqueous solution and we attribute these differences to the neglect of solvent environment in our calculations. The averaged absorption spectra for the copper(II) aqua complexes have been computed using spin-restricted density functional linear response formalism taking 100 snap shots from a trajectory of 0.48 ps. We find that the calculated spectra are significantly different, showing clear features that distinguish each coordination model. Comparison with the experimentally reported absorption spectra is made wherever it is possible and the results obtained favor the distorted fivefold-coordination arrangement for the molecular structure of the Cu(II) ion in aqueous solution. PMID:19283268

de Almeida, Katia Júlia; Murugan, N Arul; Rinkevicius, Zilvinas; Hugosson, Håkan Wilhelm; Vahtras, Olav; Agren, Hans; Cesar, Amary

2008-11-06

179

Atomic levers control pyranose ring conformations  

PubMed Central

Atomic force microscope manipulations of single polysaccharide molecules have recently expanded conformational chemistry to include force-driven transitions between the chair and boat conformers of the pyranose ring structure. We now expand these observations to include chair inversion, a common phenomenon in the conformational chemistry of six-membered ring molecules. We demonstrate that by stretching single pectin molecules (1 ? 4-linked ?-d-galactouronic acid polymer), we could change the pyranose ring conformation from a chair to a boat and then to an inverted chair in a clearly resolved two-step conversion: 4C1 ? boat ? 1C4. The two-step extension of the distance between the glycosidic oxygen atoms O1 and O4 determined by atomic force microscope manipulations is corroborated by ab initio calculations of the increase in length of the residue vector O1O4 on chair inversion. We postulate that this conformational change results from the torque generated by the glycosidic bonds when a force is applied to the pectin molecule. Hence, the glycosidic bonds act as mechanical levers, driving the conformational transitions of the pyranose ring. When the glycosidic bonds are equatorial (e), the torque is zero, causing no conformational change. However, when the glycosidic bond is axial (a), torque is generated, causing a rotation around C—C bonds and a conformational change. This hypothesis readily predicts the number of transitions observed in pyranose monomers with 1a-4a linkages (two), 1a-4e (one), and 1e-4e (none). Our results demonstrate single-molecule mechanochemistry with the capability of resolving complex conformational transitions.

Marszalek, Piotr E.; Pang, Yuan-Ping; Li, Hongbin; Yazal, Jamal El; Oberhauser, Andres F.; Fernandez, Julio M.

1999-01-01

180

Conformational Properties of ?-PrP*  

PubMed Central

Prion propagation involves a conformational transition of the cellular form of prion protein (PrPC) to a disease-specific isomer (PrPSc), shifting from a predominantly ?-helical conformation to one dominated by ?-sheet structure. This conformational transition is of critical importance in understanding the molecular basis for prion disease. Here, we elucidate the conformational properties of a disulfide-reduced fragment of human PrP spanning residues 91–231 under acidic conditions, using a combination of heteronuclear NMR, analytical ultracentrifugation, and circular dichroism. We find that this form of the protein, which similarly to PrPSc, is a potent inhibitor of the 26 S proteasome, assembles into soluble oligomers that have significant ?-sheet content. The monomeric precursor to these oligomers exhibits many of the characteristics of a molten globule intermediate with some helical character in regions that form helices I and III in the PrPC conformation, whereas helix II exhibits little evidence for adopting a helical conformation, suggesting that this region is a likely source of interaction within the initial phases of the transformation to a ?-rich conformation. This precursor state is almost as compact as the folded PrPC structure and, as it assembles, only residues 126–227 are immobilized within the oligomeric structure, leaving the remainder in a mobile, random-coil state.

Hosszu, Laszlo L. P.; Trevitt, Clare R.; Jones, Samantha; Batchelor, Mark; Scott, David J.; Jackson, Graham S.; Collinge, John; Waltho, Jonathan P.; Clarke, Anthony R.

2009-01-01

181

Conformational preferences of pseudoproline residues.  

PubMed

The conformational study on N-acetyl-N'-methylamides of oxazolidine and thiazolidine residues (Ac-Oxa-NHMe and Ac-Thz-NHMe) is carried out using ab initio HF and density functional B3LYP methods with the self-consistent reaction field method to explore the effects of the replacement of the C(gamma)H(2) group in the prolyl ring by oxygen or sulfur atoms on the conformational preferences and prolyl cis-trans isomerization in the gas phase and in solution (chloroform and water). As the solvent polarity increases, the conformations C with the C7 intramolecular hydrogen bonds become depopulated, the PPII- or PPI-like conformations F become more populated, and the cis populations increase for both Oxa and Thz dipeptides, as found for the Pro dipeptide, although the populations of backbone conformations and puckerings are different in pseudoproline and proline dipeptides. As the increase of solvent polarity, the populations of the trans/up conformations decrease for Oxa and Thz dipeptides, but they increase for the Pro dipeptide. It is found that the cis-trans isomerization proceeds through the anticlockwise rotation with omega' approximately -60 degrees about the oxazolidyl peptide bond and the clockwise rotation with omega' approximately +120 degrees about the thiazolidyl peptide bond in the gas phase and in solution, whereas the clockwise rotation is preferred for the prolyl peptide bond. The pertinent distance d(N...H-N(NHMe)) and the pyramidality of the prolyl nitrogen can describe the role of this hydrogen bond in stabilizing the transition state structure but the lower rotational barriers for Oxa and Thz dipeptides than those for the Pro dipeptide, which is observed from experiments, cannot be rationalized. The calculated cis populations and rotational barriers to the cis-trans isomerization for both Oxa and Thz dipeptides in chloroform and/or water are consistent with the experimental values. PMID:17927239

Kang, Young Kee; Park, Hae Sook

2007-10-10

182

Solvent-dependent switch of helical main-chain chirality in sergeants-and-soldiers-type poly(quinoxaline-2,3-diyl)s: effect of the position and structures of the "sergeant" chiral units on the screw-sense induction.  

PubMed

Poly(quinoxaline-2,3-diyl) copolymers bearing various "sergeant" chiral units with common "soldier" achiral units have been synthesized to investigate the efficiency of screw-sense induction and its dependence on the nature of the solvents. Optically active 2-alkoxymethyl side chains located at the 6- and 7-positions of the quinoxaline ring induced a single-handed helical conformation more efficiently than 3-methylpentyl or 2-methylbutoxy chiral side chains. Among the 2-alkoxymethyl side chains, those bearing higher 2-alkoxy groups induced a single-handed screw sense more efficiently. For instance, a monomer unit bearing (R)-2-octyloxymethyl groups stabilized the P-helix by 1.01 kJ/mol, whereas the monomer bearing (S)-2-butoxymethyl groups stabilized the M-helix by 0.59 kJ/mol. The effect of the position of the sergeant units in the polymer main chain on the screw-sense induction was also investigated using copolymers in which the positions of the sergeant units were carefully controlled by their synthesis via living polymerization. Chiral units placed sparsely could induce single-handed helical structure efficiently. Chiral units bearing 2-alkoxymethyl, 3-methylpentyl, and 2-methylbutoxy groups showed solvent-dependent helix inversion in CHCl3 and 1,1,2-trichloroethane. No helix inversion was observed in those solvents with chiral units bearing 2-butoxy or (2-methylbutoxy)methyl side chains. The 40-mer of the (R)-2-octyloxymethyl units showed P-helical structures in THF, t-BuOMe, and c-C5H11OMe, toluene, pyridine, Et3N, 1-BuOH, CHCl3, CH2Cl2, 1,4-dichlorobutane, 1,1,-dichloroethane, and 1,1,1-trichloroethane, whereas M-helical structures were induced in 1-BuCN, 1-PrCN, 1,2-dichloroethane, 1,3-dichloropropane, and 2-BuOH. PMID:23773002

Nagata, Yuuya; Yamada, Tetsuya; Adachi, Takumi; Akai, Yuto; Yamamoto, Takeshi; Suginome, Michinori

2013-07-01

183

Conformal Standard Model  

NASA Astrophysics Data System (ADS)

In recent papers we have constructed the conformal theory of metric-torsional gravitation, and in this paper we shall include the gauge fields to study the conformal U(1)× SU(2) Standard Model; we will show that the metric-torsional degrees of freedom give rise to a potential of conformal-gauge dynamical symmetry breaking: consequences are discussed.

Fabbri, Luca

2012-12-01

184

Conformational Dynamics in DNA Replication Selectivity  

NASA Astrophysics Data System (ADS)

Replicative DNA polymerases are remarkable molecular machines that carry out DNA synthesis accordingly to the Watson and Crick rules (Guanine pairs with Cytosine and Adenine with Thymidine) with high specificity or fidelity. The biochemical mechanism that dictates polymerase fidelity has its fundaments in the tight active site of replicative polymerases and the shape and size of the Watson-Crick base pairs. Pre-steady state kinetic analysis have shown that during polymerase nucleotide addition, the chemical reaction is not the rate limiting step and it was postulated that DNA polymerases suffer a conformational change from an ``open'' to a ``closed'' conformation before chemistry which is also the step responsible for their high fidelity. Crystal structures of replicative DNA polymerases demonstrated that the fingers subdomain suffers a large conformational change during catalysis and that this conformational transition aligns the polymerase active site in a proper conformation for catalysis. Recent studies using single molecule techniques and Fluorescence Resonance Energy Transfer analysis also shown that at least in the case of T7 DNA polymerase, the closure of the fingers subdomain is in part the rate limiting step associated with the high fidelity of DNA polymerases, although the overall fidelity of the reaction maybe involves an assemble of chemical steps and several conformational changes. Our current knowledge indicates that the mechanisms of enzyme specificity in DNA replication involve several energy landscapes that maybe correlated with conformational changes and active site assemblies.

Brieba, Luis G.

2007-11-01

185

Conformations of proline  

Microsoft Academic Search

The present study concerns the energies of the conformations of proline. We present results of an improved molecular mechanics calculation for ring conformations of Ac-Pro-OCHâ and for the s-cis and s-trans conformations. Internal coordinates including all torsions have been calculated from crystal coordinates for more than 40 x-ray determinations to give a consistent set of data which define proline ring

DeLos F. DeTar; Narender P. Luthra

1977-01-01

186

On the dynamics of molecular conformation  

PubMed Central

Understanding the mechanism of fast transitions between conformed states of large biomolecules is central to reconciling the dichotomy between the relatively high speed of metabolic processes and slow (random-walk based) estimates on the speed of biomolecular processes. Here we use the dynamical systems approach to suggest that the reduced time of transition between different conformations is due to features of the dynamics of molecules that are a consequence of their structural features. Long-range and local effects both play a role. Long-range molecular forces account for the robustness of final states and nonlinear processes that channel localized, bounded disturbances into collective, modal motions. Local interconnections provide fast transition dynamics. These properties are shared by a class of networked systems with strong local interconnections and long-range nonlinear forces that thus exhibit flexibility and robustness at the same time.

Mezic, Igor

2006-01-01

187

Fusion of conformal interfaces  

Microsoft Academic Search

We study the fusion of conformal interfaces in the c = 1 conformal field theory. We uncover an elegant structure reminiscent of that of black holes in supersymmetric theories. The role of the BPS black holes is played by topological interfaces, which (a) minimize the entropy function, (b) fix through an attractor mechanism one or both of the bulk radii,

C. Bachas; I. Brunner

2008-01-01

188

Crime and Conformism  

Microsoft Academic Search

We propose a simple conformism model that explains how parental education and peer pressure impact on criminal activities. We then test the model using the U.S. National Longitudinal Survey of Adolescent Health (AddHealth), which contains unique information on friendship relationships among delinquent teenagers. We find that conformity is very strong within groups of delinquents and that the higher the taste

Eleonora Patacchini; Yves Zenou

2005-01-01

189

CONSENSUS AND CONFORMITY.  

ERIC Educational Resources Information Center

|IN THIS STUDY, PROFESSOR ALLEN EMPLOYS TWO METHODS OF BREAKING GROUP CONSENSUS, AND HE MEASURES THE EFFECTS ON THE RESPONSES OF COLLEGE SUBJECTS TO BOTH OBJECTIVE AND SUBJECTIVE STIMULI. THE RESULTS SUGGEST THE NEED FOR MODIFICATION OF EXISTING THEORIES OF CONFORMITY BEHAVIOR. IN ADDITION, THESE RESULTS EMPHASIZE THE DIFFERENCES IN CONFORMITY OF…

ALLEN, VERNON L.; LEVINE, JOHN M.

190

Dynamics and Conformational Energetics of a Peptide Hormone: Vasopressin  

NASA Astrophysics Data System (ADS)

A theoretical methodology for use in conjunction with experiment was applied to the neurohypophyseal hormone lysine vasopressin for elucidation of its accessible molecular conformations and associated flexibility, conformational transitions, and dynamics. Molecular dynamics and energy minimization techniques make possible a description of the conformational properties of a peptide in terms of the precise positions of atoms, their fluctuations in time, and the interatomic forces acting on them. Analysis of the dynamic trajectory of lysine vasopressin shows the ability of a flexible peptide hormone to undergo spontaneous conformational transitions. The excursions of an individual phenylalanine residue exemplify the dynamic flexibility and multiple conformational states available to small peptide hormones and their component residues, even within constraints imposed by a cyclic hexapeptide ring.

Hagler, A. T.; Osguthorpe, D. J.; Dauber-Osguthorpe, P.; Hempel, J. C.

1985-03-01

191

Structure and Conformation of Carbohydrates  

NASA Astrophysics Data System (ADS)

The conformational analysis of monosaccharides, disaccharides, and oligosaccharides is reviewed. Conformational terms are introduced through examination of the conformations of cyclohexane and cyclopentane then applied to the pyranose, furanose , and septanose rings. Concepts such as the anomeric effect are discussed. Topics of current interest, such as hydroxymethyl group and hydroxyl group rotation and disaccharide conformations are summarized. Physical methods for studying conformation are outlined.

Grindley, T. Bruce

192

Discovering conformational sub-states relevant to protein function  

SciTech Connect

Internal motions enable proteins to explore a range of conformations, even in the vicinity of native state. The role of conformational fluctuations in the designated function of a protein is widely debated. Emerging evidence suggests that sub-groups within the range of conformations (or sub-states) contain properties that may be functionally relevant. However, low populations in these sub-states and the transient nature of conformational transitions between these sub-states present significant challenges for their identification and characterization. To overcome these challenges we have developed a new computational technique, quasi-anharmonic analysis (QAA). QAA utilizes higher-order statistics of protein motions to identify sub-states in the conformational landscape. Further, the focus on anharmonicity allows identification of conformational fluctuations that enable transitions between sub-states. QAA applied to equilibrium simulations of human ubiquitin and T4 lysozyme reveals functionally relevant sub-states and protein motions involved in molecular recognition. In combination with a reaction pathway sampling method, QAA characterizes conformational sub-states associated with cis/trans peptidyl-prolyl isomerization catalyzed by the enzyme cyclophilin A. In these three proteins, QAA allows identification of conformational sub-states, with critical structural and dynamical features relevant to protein function. Overall, QAA provides a novel framework to intuitively understand the biophysical basis of conformational diversity and its relevance to protein function.

Agarwal, Pratul K [ORNL; Ramanathan, Arvind [ORNL

2011-01-01

193

Discovering Conformational Sub-States Relevant to Protein Function  

PubMed Central

Background Internal motions enable proteins to explore a range of conformations, even in the vicinity of native state. The role of conformational fluctuations in the designated function of a protein is widely debated. Emerging evidence suggests that sub-groups within the range of conformations (or sub-states) contain properties that may be functionally relevant. However, low populations in these sub-states and the transient nature of conformational transitions between these sub-states present significant challenges for their identification and characterization. Methods and Findings To overcome these challenges we have developed a new computational technique, quasi-anharmonic analysis (QAA). QAA utilizes higher-order statistics of protein motions to identify sub-states in the conformational landscape. Further, the focus on anharmonicity allows identification of conformational fluctuations that enable transitions between sub-states. QAA applied to equilibrium simulations of human ubiquitin and T4 lysozyme reveals functionally relevant sub-states and protein motions involved in molecular recognition. In combination with a reaction pathway sampling method, QAA characterizes conformational sub-states associated with cis/trans peptidyl-prolyl isomerization catalyzed by the enzyme cyclophilin A. In these three proteins, QAA allows identification of conformational sub-states, with critical structural and dynamical features relevant to protein function. Conclusions Overall, QAA provides a novel framework to intuitively understand the biophysical basis of conformational diversity and its relevance to protein function.

Ramanathan, Arvind; Savol, Andrej J.; Langmead, Christopher J.; Agarwal, Pratul K.; Chennubhotla, Chakra S.

2011-01-01

194

Spinning conformal correlators  

NASA Astrophysics Data System (ADS)

We develop the embedding formalism for conformal field theories, aimed at doing computations with symmetric traceless operators of arbitrary spin. We use an indexfree notation where tensors are encoded by polynomials in auxiliary polarization vectors. The efficiency of the formalism is demonstrated by computing the tensor structures allowed in n-point conformal correlation functions of tensors operators. Constraints due to tensor conservation also take a simple form in this formalism. Finally, we obtain a perfect match between the number of independent tensor structures of conformal correlators in d dimensions and the number of independent structures in scattering amplitudes of spinning particles in ( d + 1)-dimensional Minkowski space.

Costa, Miguel S.; Penedones, João; Poland, David; Rychkov, Slava

2011-11-01

195

Conformational pathways in the gating of Escherichia coli mechanosensitive channel  

Microsoft Academic Search

The pathway of the gating conformational transition of Escherichia coli mechanosensitive channel was simulated, using the recently modeled open and closed structures, by targeted molecular dynamics method. The transition can be roughly viewed as a four-stage process. The initial motion under a lower tension load is predominantly elastic deformation. The opening of the inner hydrophobic pore on a higher tension

Yifei Kong; Yufeng Shen; Tiffany E. Warth; Jianpeng Ma

2002-01-01

196

Solvent dependent photophysical properties of dimethoxy curcumin  

NASA Astrophysics Data System (ADS)

Dimethoxy curcumin (DMC) is a methylated derivative of curcumin. In order to know the effect of ring substitution on photophysical properties of curcumin, steady state absorption and fluorescence spectra of DMC were recorded in organic solvents with different polarity and compared with those of curcumin. The absorption and fluorescence spectra of DMC, like curcumin, are strongly dependent on solvent polarity and the maxima of DMC showed red shift with increase in solvent polarity function (?f), but the above effect is prominently observed in case of fluorescence maxima. From the dependence of Stokes' shift on solvent polarity function the difference between the excited state and ground state dipole moment was estimated as 4.9 D. Fluorescence quantum yield (?f) and fluorescence lifetime (?f) of DMC were also measured in different solvents at room temperature. The results indicated that with increasing solvent polarity, ?f increased linearly, which has been accounted for the decrease in non-radiative rate by intersystem crossing (ISC) processes.

Barik, Atanu; Indira Priyadarsini, K.

2013-03-01

197

Solvent dependent photophysical properties of dimethoxy curcumin.  

PubMed

Dimethoxy curcumin (DMC) is a methylated derivative of curcumin. In order to know the effect of ring substitution on photophysical properties of curcumin, steady state absorption and fluorescence spectra of DMC were recorded in organic solvents with different polarity and compared with those of curcumin. The absorption and fluorescence spectra of DMC, like curcumin, are strongly dependent on solvent polarity and the maxima of DMC showed red shift with increase in solvent polarity function (?f), but the above effect is prominently observed in case of fluorescence maxima. From the dependence of Stokes' shift on solvent polarity function the difference between the excited state and ground state dipole moment was estimated as 4.9 D. Fluorescence quantum yield (?(f)) and fluorescence lifetime (?(f)) of DMC were also measured in different solvents at room temperature. The results indicated that with increasing solvent polarity, ?(f) increased linearly, which has been accounted for the decrease in non-radiative rate by intersystem crossing (ISC) processes. PMID:23314392

Barik, Atanu; Indira Priyadarsini, K

2012-12-20

198

On the effects of conformal degrees of freedom inside a neutron star  

Microsoft Academic Search

In this paper a neutron star with an inner core which undergoes a phase transition, which is characterized by conformal degrees of freedom on the phase boundary, is considered. Typical cases of such a phase transition are e.g. quantum Hall effect, superconductivity and superfluidity. Assuming the mechanical stability of this system the effects induced by the conformal degrees of freedom

F. Canfora; A. Giacomini; S. Willison

2007-01-01

199

Conformational Characteristics of Polystyrene.  

National Technical Information Service (NTIS)

Conformational energies of meso and racemic dyads of polystyrene have been computed as functions of skeletal bond rotations. Confinement of rotations of the phenyl groups to a small range within which they are nearly perpendicular to the plane defined by ...

D. Y. Yoon P. R. Sundararajan P. J. Flory

1975-01-01

200

Enhanced conformational sampling using enveloping distribution sampling.  

PubMed

To lessen the problem of insufficient conformational sampling in biomolecular simulations is still a major challenge in computational biochemistry. In this article, an application of the method of enveloping distribution sampling (EDS) is proposed that addresses this challenge and its sampling efficiency is demonstrated in simulations of a hexa-?-peptide whose conformational equilibrium encompasses two different helical folds, i.e., a right-handed 2.710?12-helix and a left-handed 314-helix, separated by a high energy barrier. Standard MD simulations of this peptide using the GROMOS 53A6 force field did not reach convergence of the free enthalpy difference between the two helices even after 500 ns of simulation time. The use of soft-core non-bonded interactions in the centre of the peptide did enhance the number of transitions between the helices, but at the same time led to neglect of relevant helical configurations. In the simulations of a two-state EDS reference Hamiltonian that envelops both the physical peptide and the soft-core peptide, sampling of the conformational space of the physical peptide ensures that physically relevant conformations can be visited, and sampling of the conformational space of the soft-core peptide helps to enhance the transitions between the two helices. The EDS simulations sampled many more transitions between the two helices and showed much faster convergence of the relative free enthalpy of the two helices compared with the standard MD simulations with only a slightly larger computational effort to determine optimized EDS parameters. Combined with various methods to smoothen the potential energy surface, the proposed EDS application will be a powerful technique to enhance the sampling efficiency in biomolecular simulations. PMID:24116601

Lin, Zhixiong; van Gunsteren, Wilfred F

2013-10-14

201

Enhanced conformational sampling using enveloping distribution sampling  

NASA Astrophysics Data System (ADS)

To lessen the problem of insufficient conformational sampling in biomolecular simulations is still a major challenge in computational biochemistry. In this article, an application of the method of enveloping distribution sampling (EDS) is proposed that addresses this challenge and its sampling efficiency is demonstrated in simulations of a hexa-?-peptide whose conformational equilibrium encompasses two different helical folds, i.e., a right-handed 2.710/12-helix and a left-handed 314-helix, separated by a high energy barrier. Standard MD simulations of this peptide using the GROMOS 53A6 force field did not reach convergence of the free enthalpy difference between the two helices even after 500 ns of simulation time. The use of soft-core non-bonded interactions in the centre of the peptide did enhance the number of transitions between the helices, but at the same time led to neglect of relevant helical configurations. In the simulations of a two-state EDS reference Hamiltonian that envelops both the physical peptide and the soft-core peptide, sampling of the conformational space of the physical peptide ensures that physically relevant conformations can be visited, and sampling of the conformational space of the soft-core peptide helps to enhance the transitions between the two helices. The EDS simulations sampled many more transitions between the two helices and showed much faster convergence of the relative free enthalpy of the two helices compared with the standard MD simulations with only a slightly larger computational effort to determine optimized EDS parameters. Combined with various methods to smoothen the potential energy surface, the proposed EDS application will be a powerful technique to enhance the sampling efficiency in biomolecular simulations.

Lin, Zhixiong; van Gunsteren, Wilfred F.

2013-10-01

202

Transport in non-conformal holographic fluids  

NASA Astrophysics Data System (ADS)

We have considered non-conformal fluid dynamics whose gravity dual is a certain Einstein dilaton system with Liouville type dilaton potential, characterized by an intrinsic parameter ?. We have discussed the Hawking-Page transition in this framework using hard-wall model and it turns out that the critical temperature of the Hawking-Page transition encapsulates a non-trivial dependence on ?. We also obtained transport coefficients such as AC conductivity, shear viscosity and diffusion constant in the hydrodynamic limit, which show non-trivial ? dependent deviations from those in conformal fluids, although the ratio of the shear viscosity to entropy density is found to saturate the universal bound. Some of the retarded correlators are also computed in the high frequency limit for case study.

Kulkarni, Shailesh; Lee, Bum-Hoon; Oh, Jae-Hyuk; Park, Chanyong; Roychowdhury, Raju

2013-03-01

203

The open pore conformation of potassium channels  

Microsoft Academic Search

Living cells regulate the activity of their ion channels through a process known as gating. To open the pore, protein conformational changes must occur within a channel's membrane-spanning ion pathway. KcsA and MthK, closed and opened K+ channels, respectively, reveal how such gating transitions occur. Pore-lining `inner' helices contain a `gating hinge' that bends by approximately 30°. In a straight

Youxing Jiang; Alice Lee; Jiayun Chen; Martine Cadene; Brian T. Chait; Roderick MacKinnon

2002-01-01

204

Conformal Collineations in String Cosmology  

NASA Astrophysics Data System (ADS)

In this paper, we study the consequences of the existence of conformal collineations (CC) for string cloud in the context of general relativity. Especially, we interest in special conformal collineation (SCC), generated by a special affine conformal collineation (SACC) in the string cloud. Some results on the restrictions imposed by a conformal collineation symmetry in the string cloud are obtained.

Baysal, Hüsnü; Camci, U.?ur; Tarhan, ?smail; Yilmaz, ?hsan; Yavuz, ?lhami; Dolgov, A.

205

Structure and Conformation of Carbohydrates  

Microsoft Academic Search

The conformational analysis of monosaccharides, disaccharides, and oligosaccharides is reviewed. Conformational terms are introduced through examination of the conformations of cyclohexane and cyclopentane then applied to the pyranose, furanose , and septanose rings. Concepts such as the anomeric effect are discussed. Topics of current interest, such as hydroxymethyl group and hydroxyl group rotation and disaccharide conformations are summarized. Physical methods

T. Bruce Grindley

2008-01-01

206

A Physical Picture of Protein Dynamics and Conformational Changes  

PubMed Central

A physical model is reviewed which explains different aspects of protein dynamics consistently. At low temperatures, the molecules are frozen in conformational substates. Their average energy is 3/2RT. Solid-state vibrations occur on a time scale of femtoseconds to nanoseconds. Above a characteristic temperature, often called the dynamical transition temperature, slow modes of motions can be observed occurring on a time scale between about 140 and 1 ns. These motions are overdamped, quasidiffusive, and involve collective motions of segments of the size of an ?-helix. Molecules performing these types of motion are in the “flexible state”. This state is reached by thermal activation. It is shown that these motions are essential for conformational relaxation. Based on this picture, a new approach is proposed to understand conformational changes. It connects structural fluctuations and conformational transitions.

Achterhold, Klaus; Croci, Simonetta; Schmidt, Marius

2008-01-01

207

Single molecule FRET to resolve conformational fluctuations in proteins  

NASA Astrophysics Data System (ADS)

Proteins fold into complex shapes that are intimately linked to their function. High-resolution techniques are capable of determining static images of these structures with atomic detail, but biological function and regulation is achieved through dynamic changes in protein conformation. Single molecule fluorescence techniques have a unique capability to detect transient molecular conformations. The power of the single molecule approach arises because it avoids the averaging over molecules and over time that are inherent in ensemble measurements. We report application of single molecule fluorescence resonance energy transfer (smFRET) to tSNARE to directly observe a conformational transition that is postulated to have an auto-regulatory function. We present a series of measurements using mutants of the proteins as well as homologues of different species in order to gain a molecular level understanding of these transitions. The techniques demonstrated here are directly applicable to investigations of conformational dynamics in other protein based macro-molecular machines.

Weninger, Keith

2005-03-01

208

Conformation of a tethered polymer in a leaky nanocavity  

NASA Astrophysics Data System (ADS)

The conformation of an ideal polymer chain confined in a box with a D×D hole is studied by N-step random walk simulations. For a polymer chain tethered inside the box, three conformational states are observed when the chain length is increased. For short chains the polymer assumes ``mushroom'' configurations. Increasing the chain length leads to a state in which the polymer fills the box. When the chain is long enough, the polymer escapes from the box, assuring an overall random walk state. Probability distributions of the free end and end-to-end distance are used to characterize polymer conformations. The escape transition is determined by the disappearance of the bimodal feature in the end-to-end probability density function. A crossover of the free energy difference between the confined and escaped states signals an escape transition analogous to the coil-globule transition of a free ideal chain.

Nakamura, Issei; Shi, An-Chang

2010-05-01

209

Protein Conformational Populations and Functionally Relevant Sub-states  

SciTech Connect

Functioning proteins do not remain fixed in a unique structure, but instead they sample a range of conformations facilitated by motions within the protein. Even in the native state, a protein exists as a collection of interconverting conformations driven by thermodynamic fluctuations. Motions on the fast time scale allow a protein to sample conformations in the nearby area of its conformational landscape, while motions on slower time scales give it access to conformations in distal areas of the landscape. Emerging evidence indicates that protein landscapes contain conformational substates with dynamic and structural features that support the designated function of the protein. Nuclear magnetic resonance (NMR) experiments provide information about conformational ensembles of proteins. X-ray crystallography allows researchers to identify the most populated states along the landscape, and computational simulations give atom-level information about the conformational substates of different proteins. This ability to characterize and obtain quantitative information about the conformational substates and the populations of proteins within them is allowing researchers to better understand the relationship between protein structure and dynamics and the mechanisms of protein function. In this Account, we discuss recent developments and challenges in the characterization of functionally relevant conformational populations and substates of proteins. In some enzymes, the sampling of functionally relevant conformational substates is connected to promoting the overall mechanism of catalysis. For example, the conformational landscape of the enzyme dihydrofolate reductase has multiple substates, which facilitate the binding and the release of the cofactor and substrate and catalyze the hydride transfer. For the enzyme cyclophilin A, computational simulations reveal that the long time scale conformational fluctuations enable the enzyme to access conformational substates that allow it to attain the transition state, therefore promoting the reaction mechanism. In the long term, this emerging view of proteins with conformational substates has broad implications for improving our understanding of enzymes, enzyme engineering, and better drug design. Researchers have already used photoactivation to modulate protein conformations as a strategy to develop a hypercatalytic enzyme. In addition, the alteration of the conformational substates through binding of ligands at locations other than the active site provides the basis for the design of new medicines through allosteric modulation.

Agarwal, Pratul K [ORNL; Burger, Virginia [University of Pittsburgh School of Medicine, Pittsburgh PA; Savol, Andrej [University of Pittsburgh School of Medicine, Pittsburgh PA; Ramanathan, Arvind [ORNL; Chennubhotla, Chakra [University of Pittsburgh School of Medicine, Pittsburgh PA

2013-01-01

210

CONFORMANCE IMPROVEMENT USING GELS  

Microsoft Academic Search

This report describes work performed during the third and final year of the project, ''Conformance Improvement Using Gels.'' Corefloods revealed throughput dependencies of permeability reduction by polymers and gels that were much more prolonged during oil flow than water flow. This behavior was explained using simple mobility ratio arguments. A model was developed that quantitatively fits the results and predicts

Randall S. Seright

2004-01-01

211

Galilean conformal and superconformal symmetries  

SciTech Connect

Firstly we discuss briefly three different algebras named as nonrelativistic (NR) conformal: Schroedinger, Galilean conformal, and infinite algebra of local NR conformal isometries. Further we shall consider in some detail Galilean conformal algebra (GCA) obtained in the limit c{yields}{infinity} from relativistic conformal algebraO(d+1, 2) (d-number of space dimensions). Two different contraction limits providing GCA and some recently considered realizations will be briefly discussed. Finally by considering NR contraction of D = 4 superconformal algebra the Galilei conformal superalgebra (GCSA) is obtained, in the formulation using complexWeyl supercharges.

Lukierski, J., E-mail: lukier@ift.uni.wroc.pl [University of Wroclaw, Institute for Theoretical Physics (Poland)

2012-10-15

212

A conformal extension theorem based on null conformal geodesics  

Microsoft Academic Search

In this article we describe the formulation of null geodesics as null conformal geodesics and their description in the tractor formalism. A conformal extension theorem through an isotropic singularity is proven by requiring the boundedness of the tractor curvature and its derivatives to sufficient order along a congruence of null conformal geodesic. This article extends earlier work by Lübbe and

Christian Lübbe

2009-01-01

213

Gradual change of conformational disorder.  

National Technical Information Service (NTIS)

The basic step of crystallization of linear macromolecules is conformational ordering. If the ordering is completed during crystallization, the entropy of fusion is a measure of the gain of conformational disorder on melting. In this lecture the possibili...

B. Wunderlich

1994-01-01

214

Conformally flat contact metric manifolds  

Microsoft Academic Search

.   A couple of classes of conformally flat contact metric manifolds have been classified. Conformally flat contact manifolds\\u000a have been characterized as hypersurfaces of 4-dimensional Kaehler Einstein (in particular, Calabi-Yau) manifolds.

Amalendu Ghosh; Themis Koufogiorgos; Ramesh Sharma

2001-01-01

215

Numerical Conformal Mapping and Applications.  

National Technical Information Service (NTIS)

Progress was made in three principal areas: (1) Conformal mapping of highly elongated polygons. Conventional methods of conformal mapping break down when applied to highly distorted regions, as arise frequently in applications. In the first year of resear...

L. N. Trefethen

1989-01-01

216

Atomic cranks and levers control sugar ring conformations  

NASA Astrophysics Data System (ADS)

In this paper we review the conformational analysis of sugar rings placed under tension during mechanical manipulations of single polysaccharide molecules with the atomic force microscope and during steered molecular dynamics simulations. We examine the role of various chemical bonds and linkages between sugar rings in inhibiting or promoting their conformational transitions by means of external forces. Small differences in the orientation of one chemical bond on the sugar ring can produce significantly different mechanical properties at the polymer level as exemplified by two polysaccharides: cellulose, composed of ?-1\\to 4 -linked D-glucose, and amylose, composed of ?-1\\to 4 -linked D-glucose. In contrast to ?-glucose rings, which are mechanically stable and produce simple entropic elasticity of the chain, ?-glucose rings flip under tension from their chair to a boat-like structure and these transitions produce deviations of amylose elasticity from the freely jointed chain model. We also examine the deformation of two mechanically complementary 1 \\to 6 -linked polysaccharides: pustulan, a ?-1\\to 6 -linked glucan, and dextran, a ?-1\\to 6 -linked glucan. Forced rotations about the C5-C6 bonds govern the elasticity of pustulan, and complex conformational transitions that involve simultaneous C5-C6 rotations and chair-boat transitions govern the elasticity of dextran. Finally, we discuss the likelihood of various conformational transitions in sugar rings in biological settings and speculate on their significance.

Zhang, Qingmin; Lee, Gwangrog; Marszalek, Piotr E.

2005-05-01

217

Conformal superspace ?-models  

NASA Astrophysics Data System (ADS)

We review recent developments in the context of two-dimensional conformally invariant ?-models. These quantum field theories play a prominent role in the covariant superstring quantization in flux backgrounds and in the analysis of disordered systems.We present supergroup WZW models as primary examples of logarithmic conformal field theories, whose structure is almost entirely determined by the underlying supergeometry. In particular, we discuss the harmonic analysis on supergroups and supercosets and point out the subtleties of Lie superalgebra representation theory that are responsible for the emergence of logarithmic representations. Furthermore, special types of marginal deformations of supergroup WZW models are studied which only exist if the Killing form is vanishing. We show how exact expressions for anomalous dimensions of boundary fields can be derived using quasi-abelian perturbation theory. Finally, the knowledge of the exact spectrum is used to motivate a duality between the OSP(4|2) symmetric Gross-Neveu model and the S3 supersphere ?-model.

Mitev, Vladimir; Quella, Thomas; Schomerus, Volker

2011-09-01

218

Mapping L1 Ligase ribozyme conformational switch  

PubMed Central

L1 Ligase (L1L)molecular switch is an in vitro optimized synthetic allosteric ribozyme that catalyzes the regioselective formation of a 5’-to-3’ phosphodiester bond, a reaction for which there is no known naturally occurring RNA catalyst. L1L serves as a proof of principle that RNA can catalyze a critical reaction for prebiotic RNA self-replication according to the RNA World hypothesis. L1L crystal structure captures two distinct conformations that differ by a re-orientation of one of the stems by around 80 Å and are presumed to correspond to the active and inactive state, respectively. It is of great interest to understand the nature of these two states in solution, and the pathway for their interconversion. In this study, we use explicit solvent molecular simulation together with a novel enhanced sampling method that utilizes concepts from network theory to map out the conformational transition between active and inactive states of L1L. We find that the overall switching mechanism can be described as a 3-state/2-step process. The first step involves a large-amplitude swing that re-orients stem C. The second step involves the allosteric activation of the catalytic site through distant contacts with stem C. Using a conformational space network representation of the L1L switch transition, it is shown that the connection between the three states follows different topographical patterns: the stem C swing step passes through a narrow region of the conformational space network, whereas the allosteric activation step covers a much wider region and a more diverse set of pathways through the network.

Giambasu, George M.; Lee, Tai-Sung; Scott, William G.; York, Darrin M.

2012-01-01

219

Substrate conformations set the rate of enzymatic acrylation by lipases.  

PubMed

Acrylates represent a class of alpha,beta-unsaturated compounds of high industrial importance. We investigated the influence of substrate conformations on the experimentally determined reaction rates of the enzyme-catalysed transacylation of methyl acrylate and derivatives by ab initio DFT B3LYP calculations and molecular dynamics simulations. The results supported a least-motion mechanism upon the sp(2) to sp(3) substrate transition to reach the transition state in the enzyme active site. This was in accordance with our hypothesis that acrylates form productive transition states from their low-energy s-sis/s-trans conformations. Apparent k(cat) values were measured for Candida antarctica lipase B (CALB), Humicola insolens cutinase and Rhizomucor miehei lipase and were compared to results from computer simulations. More potent enzymes for acryltransfer, such as the CALB mutant V190A and acrylates with higher turnover numbers, showed elevated populations of productive transition states. PMID:20301160

Syrén, Per-Olof; Hult, Karl

2010-04-12

220

Conformal higher spin theory  

NASA Astrophysics Data System (ADS)

We construct gauge theory of interacting symmetric traceless tensors of all ranks /s=0,1,2,3,... which generalizes Weyl-invariant dilaton gravity to the higher spin case, in any dimension /d>2. The action is given by the trace of the projector to the subspace with positive eigenvalues of an arbitrary Hermitian differential operator H, and the symmetric tensors emerge after expansion of the latter in power series in derivatives. After decomposition in perturbative series around conformally flat point H=? with Euclidean metric, the action functional describes conformal higher spin theory. Namely, the linear in fluctuation term cancels, while the one quadratic in fluctuation breaks up as a sum of conformal higher spin theories, the latter being free gauge theories of symmetric traceless tensors of rank /s with actions of /d-4+2s order in derivatives (in odd dimensions they are boundary terms), for all integer /s, introduced in 4d case by Fradkin and Tseytlin and studied at the cubic order level by Fradkin and Linetsky. Higher orders in interaction are well-defined. The action appears to be the unique functional invariant w.r.t. general similarity transformations H'=e??†He??, the latter invariance plays the role of gauge symmetry group of the model. In the framework of the perturbative decomposition, the Hermitian part of /? gauges away the trace parts of the symmetric tensors parameterizing the fluctuation, while the anti-Hermitian one provides standard linearized gauge transformations of conformal higher spin fields. The action can be calculated as a semiclassical series in /? which counts the number of space-time derivatives and thereby exhibits itself as a parameter of low-energy expansion, like /sqrt(?') in string theory, in so doing the classical term is given by the volume of the domain /H(x,p)>0 (where /H(x,p) is the Weyl symbol of H), it does not contain derivatives and is interpreted as a cosmological term. At the same time, further terms of the /?-expansion are given by integrals of distributions localized on the constraint surface /H(x,p)=0, and the conformal higher spin-/s action arises from the ?d-4+2s-correction. The full gauge invariance of the model is interpreted as covariance algebra of generalized Klein-Gordon equation H?>=0 for complex scalar field /?.

Segal, Arkady Y.

2003-08-01

221

Solid state and solution conformations of a hybrid alphagammaalphaalphagammaalpha hexapeptide. Characterization of a backbone expanded analog of the alpha-polypeptide 3(10)-helix.  

PubMed

The stereochemically constrained gamma amino acid residue gabapentin (1-(aminomethyl)cyclohexaneacetic acid, Gpn) has been incorporated into a host alpha-peptide sequence. The structure of a hybrid alphagammaalphaalphagammaalpha peptide, Boc-Leu-Gpn-Aib-Leu-Gpn-Aib-OMe in crystals reveals a continuous helical conformation stabilized by three intramolecular 4 --> 1 C(12) hydrogen bonds across the alphagamma/alphagamma segments and one C(10) hydrogen bond across the central alphaalpha segment. This conformation corresponds to an expanded analog of the canonical all-alpha polypeptide 3(10)-helix, with insertion of two additional backbone atoms at each gamma residue. Solvent dependence of NH chemical shifts in CDCl(3) solution are consistent with conformation in which the NH groups of Aib (3), Leu (4), Gpn (5), and Aib (6) are hydrogen bonded, a feature observed in the solid state. The nonsequential NOEs between Gpn (2) NH <--> Leu (4) NH and Gpn (2) NH <--> Gpn (5) NH support the presence of additional conformations in solution. Temperature-dependent line broadening of NH resonances confirms the occurrence of rapid exchange between multiple conformations at room temperature. Two conformational models which rationalize the observed nonsequential NOEs are presented, both of which contain three hydrogen bonds and are consistent with the known stereochemical preferences of the Gpn residue. PMID:18767124

Chatterjee, Sunanda; Vasudev, Prema G; Raghothama, Srinivasarao; Shamala, Narayanaswamy; Balaram, Padmanabhan

2008-01-01

222

An Expression of Periodic Phenomena of Fashion on Sexual Selection Model with Conformity Genes and Memes  

NASA Astrophysics Data System (ADS)

It is generally thought that living things have trends in their preferences. The mechanism of occurrence of another trends in successive periods is concerned in their conformity. According to social impact theory, the minority is always exists in the group. There is a possibility that the minority make the transition to the majority by conforming agents. Because of agent's promotion of their conform actions, the majority can make the transition. We proposed an evolutionary model with both genes and memes, and elucidated the interaction between genes and memes on sexual selection. In this paper, we propose an agent model for sexual selection imported the concept of conformity. Using this model we try an environment where male agents and female agents are existed, we find that periodic phenomena of fashion are expressed. And we report the influence of conformity and differentiation on the transition of their preferences.

Mutoh, Atsuko; Tokuhara, Shinya; Kanoh, Masayoshi; Oboshi, Tamon; Kato, Shohei; Itoh, Hidenori

223

Theory for the conformational changes of double-stranded chain molecules  

NASA Astrophysics Data System (ADS)

We develop statistical mechanical theory to predict the thermodynamic properties of chain molecules having noncovalent double-stranded conformations, as in RNA molecules and ?-sheets in proteins. Sequence dependence and excluded volume interactions are explicitly taken into account. We classify conformations by their polymer graphs and enumerate all the conformations corresponding to each graph by a recently developed matrix method [S-J. Chen and K. A. Dill, J. Chem. Phys. 103, 5802 (1995)]. All such graphs are summed by a recursive method. Tests against exact computer enumeration for short chains on a 2D lattice show that the density of states and partition function are given quite accurately. So far, we have explored two classes of conformations; hairpins, which model small ?-sheets, and RNA secondary structures. The main folding transition is predicted to be quite different for these two conformational classes: the hairpin transition is two-state while the RNA secondary structure transition is one-state for homopolymeric chains.

Chen, Shi-Jie; Dill, Ken A.

1998-09-01

224

Helix formation via conformation diffusion search  

NASA Astrophysics Data System (ADS)

The helix-coil transition kinetics of an -helical peptide were investigated by time-resolved infrared spectroscopy coupled with laser-induced temperature-jump initiation method. Specific isotope labeling of the amide carbonyl groups with 13C at selected residues was used to obtain site-specific information. The relaxation kinetics following a temperature jump, obtained by probing the amide I' band of the peptide backbone, exhibit nonexponential behavior and are sensitive to both initial and final temperatures. These data are consistent with a conformation diffusion process on the folding energy landscape, in accord with a recent molecular dynamics simulation study.

Huang, Cheng-Yen; Getahun, Zelleka; Zhu, Yongjin; Klemke, Jason W.; Degrado, William F.; Gai, Feng

2002-03-01

225

Conformal optical design  

NASA Astrophysics Data System (ADS)

Optics with external surfaces that deviate from conventional forms to better satisfy the needs of host platform are known as conformal optics. These external surfaces generate significant amounts of aberration that may be compensated with additional corrector elements. This dissertation introduces a new tool for the design of correctors for non-rotationally symmetric optical systems. This is accomplished through the derivation of two new differential equations using an approach similar to that of Wassermann and Wolf. The new aspheric design equations are derived without the assumption of axial symmetry and may be used to precisely control a ray bundle. Solving the new design equations produces the surface profiles of two aspheric optical surfaces which make a non-rotationally symmetric system aplanatic. The aplanatic system may contain tilted and decentered elements, or optical elements without rotational symmetry before and after the two aspheric surfaces. As coma and spherical aberration can be significant in conformal windows, these equations are powerful for producing starting points and developing a design. To validate the new equations, they were implemented in a Code V RTM macro called the Generalized Aspheric design Program (GAP). This macro is used in the design of a variety of non-rotationally symmetric optical systems to create a diffraction limited field of view. These include a system with an elliptical dome with a decentered inside surface, a system containing cylindrical elements, and a system with a toroidal conformal window. In all cases, GAP is able to directly generate corrector surfaces. For comparison, the classical Wassermann-Wolf equations were also implemented in a Code V macro for the design of rotationally symmetric systems.

Knapp, David James

226

Conformity, political participation, and economic rewards: The case of Chinese private entrepreneurs  

Microsoft Academic Search

Using institutional and resource dependence theories as the conceptual framework, this study identifies three forms of conformity—political,\\u000a economic, and social—that can affect the level of private entrepreneurs’ formal political participation in a transition economy.\\u000a Data from a 2004 national-wide survey of 3,012 private firms in China show that political conformity (indicated by membership\\u000a in the ruling party), economic conformity (amount

Ying Chen; David Touve

2011-01-01

227

Observation of a Distinct Transition in the Mode of Interconversion of Ring Pucker Conformers in Non-Crystalline D-Ribose-2'-d from H-2 NMR Spin-Alignment  

SciTech Connect

Internal motions of D-ribose selectively 2H-labeled at the 2 position were measured using solid state 2H NMR experiments. A sample of D-ribose-2-d was prepared in a hydrated, non-crystalline amorphous state in an effort to reduce effects of crystal-packing. Between temperatures of -60 and -74?C the C2?H2 bond was observed to undergo two kinds of motions which were similar to those of C2?H2/H2 found previously in crystalline deoxythymidine (Hiyama et al. (1989) J. Am. Chem. Soc., 111, 8609-8613): (1) nanosecond motion of small angular displacement with an apparent activation energy of 3.6? 0.7 kcal/mol, and (2) millisecond to microsecond motion of large amplitude with an apparent activation energy≥4 kcal/mol. At -74?C, the slow, large-amplitude motion was best characterized as a two-site jump with a correlation time on the millisecond time scale, whereas at -60?C it was diffusive on the microsecond time scale. The slow, large-amplitude motions of the C2?H2 bond are most likely from interconversions between C2-endo and C3-endo by way of the O4-endo conformation, whereas the fast, small-amplitude motions are probably librations of the C2?H2 bond within the C2-endo and C3-endo potential energy minima.

Liwang, Andy C. (Texas A& amp; M University); McCready, David E. (BATTELLE (PACIFIC NW LAB)); Drobny, Gary P. (University of Washington); Reid, Brian R. (Washington University); Kennedy, Michael A. (BATTELLE (PACIFIC NW LAB))

2003-07-01

228

Metamaterials with conformational nonlinearity  

NASA Astrophysics Data System (ADS)

Within a decade of fruitful development, metamaterials became a prominent area of research, bridging theoretical and applied electrodynamics, electrical engineering and material science. Being man-made structures, metamaterials offer a particularly useful playground to develop interdisciplinary concepts. Here we demonstrate a novel principle in metamaterial assembly which integrates electromagnetic, mechanical, and thermal responses within their elements. Through these mechanisms, the conformation of the meta-molecules changes, providing a dual mechanism for nonlinearity and offering nonlinear chirality. Our proposal opens a wide road towards further developments of nonlinear metamaterials and photonic structures, adding extra flexibility to their design and control.

Lapine, Mikhail; Shadrivov, Ilya V.; Powell, David A.; Kivshar, Yuri S.

2011-11-01

229

The QCD string spectrum and conformal field theory  

SciTech Connect

The low energy excitation spectrum of the critical Wilson surface is discussed between the roughening transition and the continuum limit of lattice QCD. The fine structure of the spectrum is interpreted within the framework of two-dimensional conformal field theory.

Keisuke Jimmy Juge; Julius Kuti; Colin Morningstar

2002-12-19

230

Conformational distributions of unfolded polypeptides from novel NMR techniques  

NASA Astrophysics Data System (ADS)

How the information content of an unfolded polypeptide sequence directs a protein towards a well-formed three-dimensional structure during protein folding remains one of the fundamental questions in structural biology. Unfolded proteins have recently attracted further interest due to their surprising prevalence in the cellular milieu, where they fulfill not only central regulatory functions, but also are implicated in diseases involving protein aggregation. The understanding of both the protein folding transition and these often natively unfolded proteins hinges on a more detailed experimental characterization of the conformations and conformational transitions in the unfolded state. This description is intrinsically very difficult due to the very large size of the conformational space. In principle, solution NMR can monitor unfolded polypeptide conformations and their transitions at atomic resolution. However, traditional NMR parameters such as chemical shifts, J couplings, and nuclear Overhauser enhancements yield only rather limited and often qualitative descriptions. This situation has changed in recent years by the introduction of residual dipolar couplings and paramagnetic relaxation enhancements, which yield a high number of well-defined, quantitative parameters reporting on the averages of local conformations and long-range interactions even under strongly denaturing conditions. This information has been used to obtain plausible all-atom models of the unfolded state at increasing accuracy. Currently, the best working model is the coil model, which derives amino acid specific local conformations from the distribution of amino acid torsion angles in the nonsecondary structure conformations of the protein data bank. Deviations from the predictions of such models can often be interpreted as increased order resulting from long-range contacts within the unfolded ensemble.

Meier, Sebastian; Blackledge, Martin; Grzesiek, Stephan

2008-02-01

231

Conformer Selective and Vibrationally Mediated Photodissociation Study of Propanal Cation  

NASA Astrophysics Data System (ADS)

We report the conformationally and vibrationally selected imaging study of propanal obtained by resonance-enhanced multiphoton ionization (REMPI). The photoelectron spectra, employing the (2+1) ionization via the (n, 3s) Rydberg transitions in the range from 365 to 371 nm, confirm that there are two stable conformer origins in the lowest ionic state, the cis conformer with a co-planar CCCO geometry and a gauche conformer with a 119° CCCO dihedral angle. We also study the photodissociation dynamics of propanal cation initially prepared in some certain vibrational modes or conformation. The product kinetic energy distributions for the H elimination channels are bimodal, and the two peaks are readily assigned to propanal cation + H and hydroxyallyl cation + H. The ratio of the fast product with respect to the whole product is varied according to different vibrational mode preparation. However, cis form appears the lowest and gauche form yield the highest ratio. Full multiple spawning dynamical calculations show that distinct ultrafast dynamics in the excited state leads to internal conversion to the ground state in isolated regions of the potential surface for the two conformers, and from these distinct regions, conformer interconversion does not effectively compete with dissociation.

Shen, Lei; Kim, Myung Hwa; Zhang, Bailin; Suits, Arthur G.

2009-06-01

232

Wheel-rail dynamics with closely conformal contact Part 1: dynamic modelling and stability analysis  

Microsoft Academic Search

Observations on the Vancouver mass transit system suggest that noise, vibration and corrugation of the rail appear to be associated with close conformity between the transverse profiles of the wheel and rail. To investigate this, a dynamic model of the wheel and rail under conditions of close conformity has been developed. Previous work has suggested that motion of the wheel

A Bhaskar; K L Johnson; G D Wood; J Woodhouse

1997-01-01

233

Folding and unfolding of a triple-branch DNA molecule with four conformational states  

Microsoft Academic Search

Single-molecule experiments provide new insights into biological processes hitherto not accessible by measurements performed on bulk systems. We report on a study of the kinetics of a triple-branch DNA molecule with four conformational states by pulling experiments with optical tweezers and theoretical modelling. Three distinct force rips associated with different transitions between the conformational states are observed in the folding

Sandra Engel; Anna Alemany; Nuria Forns; Philipp Maass; Felix Ritort

2011-01-01

234

Targeting Inactive Enzyme Conformation  

PubMed Central

There has been considerable interest in protein tyrosine phosphatase 1B (PTP1B) as a therapeutic target for diabetes, obesity, as well as cancer. Identifying inhibitory compounds with good bioavailability is a major challenge of drug discovery programs targeted toward PTPs. Most current PTP active site-directed pharmacophores are negatively charged pTyr mimetics which cannot readily enter the cell. This lack of cell permeability limits the utility of such compounds in signaling studies and further therapeutic development. We identify aryl diketoacids as novel pTyr surrogates and show that neutral amide-linked aryl diketoacid dimers also exhibit excellent PTP inhibitory activity. Kinetic studies establish that these aryl diketoacid derivatives act as noncompetitive inhibitors of PTP1B. Crystal structures of ligand-bound PTP1B reveal that both the aryl diketoacid and its dimeric derivative bind PTP1B at the active site, albeit with distinct modes of interaction, in the catalytically inactive, WPD loop open conformation. Furthermore, dimeric aryl diketoacids are cell permeable and enhance insulin signaling in hepatoma cells, suggesting that targeting the inactive conformation may provide a unique opportunity for creating active site-directed PTP1B inhibitors with improved pharmacological properties.

Liu, Sijiu; Zeng, Li-Fan; Wu, Li; Yu, Xiao; Xue, Ting; Gunawan, Andrea M.; Ya-Qiu, Long; Zhang, Zhong-Yin

2009-01-01

235

Conformally symmetric traversable wormholes  

SciTech Connect

Exact solutions of traversable wormholes are found under the assumption of spherical symmetry and the existence of a nonstatic conformal symmetry, which presents a more systematic approach in searching for exact wormhole solutions. In this work, a wide variety of solutions are deduced by considering choices for the form function, a specific linear equation of state relating the energy density and the pressure anisotropy, and various phantom wormhole geometries are explored. A large class of solutions impose that the spatial distribution of the exotic matter is restricted to the throat neighborhood, with a cutoff of the stress-energy tensor at a finite junction interface, although asymptotically flat exact solutions are also found. Using the 'volume integral quantifier', it is found that the conformally symmetric phantom wormhole geometries may, in principle, be constructed by infinitesimally small amounts of averaged null energy condition violating matter. Considering the tidal acceleration traversability conditions for the phantom wormhole geometry, specific wormhole dimensions and the traversal velocity are also deduced.

Boehmer, Christian G.; Harko, Tiberiu; Lobo, Francisco S. N. [Institute of Cosmology and Gravitation, University of Portsmouth, Portsmouth PO1 2EG (United Kingdom); Department of Physics and Center for Theoretical and Computational Physics, University of Hong Kong, Pok Fu Lam Road, Hong Kong (China); Institute of Cosmology and Gravitation, University of Portsmouth, Portsmouth PO1 2EG, United Kingdom and Centro de Astronomia e Astrofisica da Universidade de Lisboa, Campo Grande, Ed. C8 1749-016 Lisbon (Portugal)

2007-10-15

236

Synthesis, molecular conformation, vibrational and electronic transition, isometric chemical shift, polarizability and hyperpolarizability analysis of 3-(4-methoxy-phenyl)-2-(4-nitro-phenyl)-acrylonitrile: a combined experimental and theoretical analysis.  

PubMed

This work presents the synthesis and characterization of a novel compound, 3-(4-methoxy-phenyl)-2-(4-nitro-phenyl)-acrylonitrile (abbreviated as 3-(4MP)-2-(4-NP)-AN, C(16)H(12)N(2)O(3)). The spectroscopic properties of the compound were examined by FT-IR, UV-vis and NMR ((1)H and (13)C) techniques. FT-IR spectrum in solid state was observed in the region 4000-400 cm(-1). The UV-vis absorption spectrum of the compound which dissolved in chloroform was recorded in the range of 200-800 nm. The (1)H and (13)C NMR spectra were recorded in CDCl(3) solution. To determine lowest-energy molecular conformation of the title molecule, the selected torsion angle is varied every 10° and molecular energy profile is calculated from 0° to 360°. The structural and spectroscopic data of the molecule in the ground state were calculated using density functional theory (DFT) employing B3LYP/6-31G(d,p) basis set. The dipole moment, linear polarizability and first hyperpolarizability values were also computed using the same basis set. A study on the electronic properties, such as HOMO and LUMO energies, were performed by time-dependent DFT (TD-DFT) approach. The HOMO and LUMO analysis were used to elucidate information regarding charge transfer within the molecule. The vibrational wavenumbers were calculated and scaled values were compared with experimental FT-IR spectrum. The complete assignments were performed on the basis of the experimental results and total energy distribution (TED) of the vibrational modes, calculated with scaled quantum mechanics (SQM) method. Isotropic chemical shifts were calculated using the gauge-invariant atomic orbital (GIAO) method. Comparison of the calculated frequencies, NMR chemical shifts, absorption wavelengths with the experimental values revealed that DFT and TD-DFT method produce good results. The linear polarizabilities and first hyperpolarizabilities of the studied molecule indicate that the title compound can be used as a good nonlinear optical material. The thermodynamic properties of the studied compound at different temperatures were calculated, revealing the correlations between standard heat capacity, standard entropy, standard enthalpy changes and temperatures. PMID:21856218

Asiri, Abdullah Mohamed; Karabacak, Mehmet; Kurt, Mustafa; Alamry, Khalid A

2011-07-28

237

The Minkowski and conformal superspaces  

SciTech Connect

We define complex Minkowski superspace in four dimensions as the big cell inside a complex flag supermanifold. The complex conformal supergroup acts naturally on this superflag, allowing us to interpret it as the conformal compactification of complex Minkowski superspace. We then consider real Minkowski superspace as a suitable real form of the complex version. Our methods are group theoretic, based on the real conformal supergroup and its Lie superalgebra.

Fioresi, R.; Lledo, M. A.; Varadarajan, V. S. [Dipartimento di Matematica, Universita di Bologna, Piazza di Porta S. Donato, 5, 40126 Bologna (Italy); Departament de Fisica Teorica, Universitat de Valencia, E-46100 Burjassot (Valencia), Spain and IFIC, C/Dr. Moliner, 50, E-46100 Burjassot (Valencia) (Spain); Department of Mathematics, UCLA, Los Angeles, California 90095-1555 (United States)

2007-11-15

238

Electronically Rich N-Substituted Tetrahydroisoquinoline 3-Carboxylic Acid Esters: Concise Synthesis and Conformational Studies.  

PubMed

Recent work in our laboratory has shown that the highly substituted, electronically rich 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (THIQ3CA) scaffold is a key building block for a novel class of promising anticoagulants (Al-Horani et al. J. Med. Chem.2011, 54, 6125-6138). The synthesis of THIQ3CA analogs, especially containing specific, electronically rich substituents, has been a challenge and essentially no efficient methods have been reported in the literature. We describe three complementary, glycine donor-based strategies for high yielding synthesis of highly substituted, electronically rich THIQ3CA esters. Three glycine donors studied herein include hydantoin 1, (±)-Boc-?-phosphonoglycine trimethyl ester 2 and (±)-Z-?-phosphonoglycine trimethyl ester 3. Although the synthesis of THIQ3CA analogs could be achieved using either of the three, an optimal, high yielding approach for the desired THIQ3CA esters was best achieved using 3 in three mild, efficient steps. Using this approach, a focused library of advanced N-arylacyl, N-arylalkyl, and bis-THIQ3CA analogs was synthesized. Variable temperature and solvent-dependent NMR chemical shift studies indicated the presence of two major conformational rotamers in 3:1 proportion for N-arylacyl-THIQ3CA analogs, which were separated by a high kinetic barrier of ~17 kcal/mol. In contrast, N-arylalkyl and bis-THIQ3CA variants displayed no rotamerism, which implicates restricted rotation around the amide bond as the origin for high-barrier conformational interconversion. This phenomenon is of major significance because structure-based drug design typically utilizes only one conformation. Overall, the work presents fundamental studies on the synthesis and conformational properties of highly substituted, electronically rich THIQ3CA analogs. PMID:22665943

Al-Horani, Rami A; Desai, Umesh R

2012-01-10

239

Electronically Rich N-Substituted Tetrahydroisoquinoline 3-Carboxylic Acid Esters: Concise Synthesis and Conformational Studies  

PubMed Central

Recent work in our laboratory has shown that the highly substituted, electronically rich 1,2,3,4–tetrahydroisoquinoline–3–carboxylic acid (THIQ3CA) scaffold is a key building block for a novel class of promising anticoagulants (Al-Horani et al. J. Med. Chem. 2011, 54, 6125–6138). The synthesis of THIQ3CA analogs, especially containing specific, electronically rich substituents, has been a challenge and essentially no efficient methods have been reported in the literature. We describe three complementary, glycine donor-based strategies for high yielding synthesis of highly substituted, electronically rich THIQ3CA esters. Three glycine donors studied herein include hydantoin 1, (±)-Boc-?-phosphonoglycine trimethyl ester 2 and (±)-Z-?-phosphonoglycine trimethyl ester 3. Although the synthesis of THIQ3CA analogs could be achieved using either of the three, an optimal, high yielding approach for the desired THIQ3CA esters was best achieved using 3 in three mild, efficient steps. Using this approach, a focused library of advanced N-arylacyl, N-arylalkyl, and bis-THIQ3CA analogs was synthesized. Variable temperature and solvent-dependent NMR chemical shift studies indicated the presence of two major conformational rotamers in 3:1 proportion for N–arylacyl–THIQ3CA analogs, which were separated by a high kinetic barrier of ~17 kcal/mol. In contrast, N–arylalkyl and bis–THIQ3CA variants displayed no rotamerism, which implicates restricted rotation around the amide bond as the origin for high-barrier conformational interconversion. This phenomenon is of major significance because structure-based drug design typically utilizes only one conformation. Overall, the work presents fundamental studies on the synthesis and conformational properties of highly substituted, electronically rich THIQ3CA analogs.

Al-Horani, Rami A.; Desai, Umesh R.

2012-01-01

240

Conformally flat spherically symmetric spacetimes  

NASA Astrophysics Data System (ADS)

We deduce a simple expression for the Kretschmann curvature scalar of a conformally flat spacetime with a perfect fluid. Conformally flat, static, spherically symmetric spacetimes are investigated in various coordinate systems. The equation for a vanishing Weyl tensor and Einstein's field equations are integrated in curvature coordinates. We find conformally flat generalizations of the de Sitter spacetime and give new analyses of the internal Schwarzschild spacetime and texture-dominated spacetimes. The spacetimes are described in curvature coordinates, isotropic coordinates and in conformally flat spacetime coordinates.

Grøn, Øyvind; Johannesen, Steinar

2013-08-01

241

A conformational intermediate in glutamate receptor activation.  

PubMed

Ionotropic glutamate receptors (iGluRs) transduce the chemical signal of neurotransmitter release into membrane depolarization at excitatory synapses in the brain. The opening of the transmembrane ion channel of these ligand-gated receptors is driven by conformational transitions that are induced by the association of glutamate molecules to the ligand-binding domains (LBDs). Here, we describe the crystal structure of a GluA2 LBD tetramer in a configuration that involves an ?30° rotation of the LBD dimers relative to the crystal structure of the full-length receptor. The configuration is stabilized by an engineered disulfide crosslink. Biochemical and electrophysiological studies on full-length receptors incorporating either this crosslink or an engineered metal bridge show that this LBD configuration corresponds to an intermediate state of receptor activation. GluA2 activation therefore involves a combination of both intra-LBD (cleft closure) and inter-LBD dimer conformational transitions. Overall, these results provide a comprehensive structural characterization of an iGluR intermediate state. PMID:23931998

Lau, Albert Y; Salazar, Héctor; Blachowicz, Lydia; Ghisi, Valentina; Plested, Andrew J R; Roux, Benoît

2013-08-01

242

Fe-heme conformations in ferric myoglobin.  

PubMed Central

X-ray absorption near-edge structure (XANES) spectra of ferric myoglobin from horse heart have been acquired as a function of pH (between 5.3 and 11.3). At pH = 11.3 temperature-dependent spectra (between 20 and 293 K) have been collected as well. Experimental data solve three main conformations of the Fe-heme: the first, at low pH, is related to high-spin aquomet-myoglobin (Mb+OH2). The other two, at pH 11.3, are related to hydroxymet-myoglobin (Mb+OH-), and are in thermal equilibrium, corresponding to high- and low-spin Mb+OH-. The structure of the three Fe-heme conformations has been assigned according to spin-resolved multiple scattering simulations and fitting of the XANES data. The chemical transition between Mb+OH2 and high-spin Mb+OH-, and the spin transition of Mb+OH-, are accompanied by changes of the Fe coordination sphere due to its movement toward the heme plane, coupled to an increase of the axial asymmetry.

Longa, S D; Pin, S; Cortes, R; Soldatov, A V; Alpert, B

1998-01-01

243

Conformal Aspects of QCD  

SciTech Connect

Theoretical and phenomenological evidence is now accumulating that the QCD coupling becomes constant at small virtuality; i.e., {alpha}{sub s}(Q{sup 2}) develops an infrared fixed point in contradiction to the usual assumption of singular growth in the infrared. For example, the hadronic decays of the {tau} lepton can be used to determine the effective charge {alpha}{sub {tau}}(m{sub {tau}{prime}}{sup 2}) for a hypothetical {tau}-lepton with mass in the range 0 < m{sub {tau}{prime}} < m{sub {tau}}. The {tau} decay data at low mass scales indicates that the effective charge freezes at a value of s = m{sub {tau}{prime}}{sup 2} of order 1 GeV{sup 2} with a magnitude {alpha}{sub {tau}} {approx} 0.9 {+-} 0.1. The near-constant behavior of effective couplings suggests that QCD can be approximated as a conformal theory even at relatively small momentum transfer and why there are no significant running coupling corrections to quark counting rules for exclusive processes. The AdS/CFT correspondence of large N{sub c} supergravity theory in higher-dimensional anti-de Sitter space with supersymmetric QCD in 4-dimensional space-time also has interesting implications for hadron phenomenology in the conformal limit, including an all-orders demonstration of counting rules for exclusive processes and light-front wavefunctions. The utility of light-front quantization and light-front Fock wavefunctions for analyzing nonperturbative QCD and representing the dynamics of QCD bound states is also discussed.

Brodsky, S

2003-11-19

244

A Conformal Extension Theorem based on Null Conformal Geodesics  

Microsoft Academic Search

In this article we describe the formulation of null geodesics as null conformal geodesics and their description in the tractor formalism. A conformal extension theorem through an isotropic singularity is proven by requiring the boundedness of the tractor curvature and its deriva- tives to sufficient order along a congruence of null conformalgeodesic. This article extends earlier work by Tod and

Christian Lubbe

245

The Principle of Maximum Conformality  

SciTech Connect

A key problem in making precise perturbative QCD predictions is the uncertainty in determining the renormalization scale of the running coupling {alpha}{sub s}({mu}{sup 2}). It is common practice to guess a physical scale {mu} = Q which is of order of a typical momentum transfer Q in the process, and then vary the scale over a range Q/2 and 2Q. This procedure is clearly problematic since the resulting fixed-order pQCD prediction will depend on the renormalization scheme, and it can even predict negative QCD cross sections at next-to-leading-order. Other heuristic methods to set the renormalization scale, such as the 'principle of minimal sensitivity', give unphysical results for jet physics, sum physics into the running coupling not associated with renormalization, and violate the transitivity property of the renormalization group. Such scale-setting methods also give incorrect results when applied to Abelian QED. Note that the factorization scale in QCD is introduced to match nonperturbative and perturbative aspects of the parton distributions in hadrons; it is present even in conformal theory and thus is a completely separate issue from renormalization scale setting. The PMC provides a consistent method for determining the renormalization scale in pQCD. The PMC scale-fixed prediction is independent of the choice of renormalization scheme, a key requirement of renormalization group invariance. The results avoid renormalon resummation and agree with QED scale-setting in the Abelian limit. The PMC global scale can be derived efficiently at NLO from basic properties of the PQCD cross section. The elimination of the renormalization scheme ambiguity using the PMC will not only increases the precision of QCD tests, but it will also increase the sensitivity of colliders to new physics beyond the Standard Model.

Brodsky, Stanley J; /SLAC; Giustino, Di; /SLAC

2011-04-05

246

Replacement between conformity and counter-conformity in consumption decisions.  

PubMed

This study assessed, in a Chinese context, how self-esteem interacts with perceived similarity and uniqueness to yield cognitive dissonance, and whether the dissonance leads to self-reported conformity or counter-conformity behavior. Participants were 408 respondents from 4 major Chinese cities (M age = 33.0 yr., SD = 4.3; 48% men). Self-perceptions of uniqueness, similarity, cognitive dissonance, self-esteem and need to behave in conformity or counter-conformity were measured. A theoretical model was assessed in four situations, relating the ratings of self-esteem and perceived similarity/uniqueness to the way other people at a wedding were dressed, and the resultant cognitive dissonance and conformity/ counter-conformity behavior. Regardless of high or low self-esteem, all participants reported cognitive dissonance when they were told that they were dressed extremely similarly to or extremely differently from the other people attending the wedding. However, the conforming/counter-conforming strategies used by participants to resolve the cognitive dissonance differed. When encountering dissonance induced by the perceived extreme uniqueness of dress, participants with low self-esteem tended to say they would dress next time so as to conform with the way others were dressed, while those with high self-esteem indicated they would continue their counter-conformity in attire. When encountering dissonance induced by the perceived extreme similarity to others, both those with high and low self-esteem tended to say they would dress in an unorthodox manner to surprise other people in the future. PMID:23654033

Chou, Ting-Jui; Chang, En-Chung; Dai, Qi; Wong, Veronica

2013-02-01

247

Observing Conformational Changes of Individual RNA Molecules Using Confocal Microscopy  

NASA Astrophysics Data System (ADS)

Recent years have seen enormous advances in single molecule detection and spectroscopy by laser-induced fluorescence. Without a doubt, the most exciting applications are in the area of Biological Physics, as the technique can readily be applied to investigations of individual biological molecules under physiological conditions. Biological macromolecules are complex physical systems that are characterized by a huge number of conformational states, and transitions among these states are intimately linked to their function. Using single molecule spectroscopy, time trajectories of physical observables can be obtained from single molecules, and conformational heterogeneity and dynamics can be investigated in a direct fashion. As an example, we discuss the measurement of conformational changes of individual 3-helix junction RNA molecules induced by the binding of Mg2+ ions. The transition from an open to a folded configuration was monitored by the change of fluorescence resonance energy transfer in a pair of dye molecules attached to different ends of two helices in the RNA junction. The two conformational states of the RNA can be clearly distinguished at the single molecule level, and transitions between the states can be monitored on the millisecond time scale.

Ulrich Nienhaus, G.; Kim, Harold D.; Chu, Steven; Ha, Taekjip; Orr, Jeffrey W.; Williamson, James R.

2001-09-01

248

Curvature Flow in Conformal Mapping  

Microsoft Academic Search

We use a simple example to introduce a notion of curvature ?ow in the conformal mapping of polyhedral surfaces. The inquiry was motivated by experiments with discrete conformal maps in the sense of circle packing. We describe the classical theory behind these ?ows and demonstrate how to modify the Schwarz-Christofiel method to obtain classical numerical conflrmation. We close with some

Charles R. Collins; Tobin A. Driscoll; Kenneth Stephenson

249

Conformality of the Apollonian Metric  

Microsoft Academic Search

The Apollonian metric aD of a domain D R n is rarely con- formal. In fact, if it is conformal at one point then D is, up to a Mobius transformation, a complement of a convex body of constant width and if it is conformal at two points then D is a ball. We consider a quantity that measures the

Zair Ibragimov

2003-01-01

250

Einstein Gravity from Conformal Gravity  

Microsoft Academic Search

We show that that four dimensional conformal gravity plus a simple Neumann boundary condition can be used to get the semiclassical (or tree level) wavefunction of the universe of four dimensional asymptotically de-Sitter or Euclidean anti-de Sitter spacetimes. This simple Neumann boundary condition selects the Einstein solution out of the more numerous solutions of conformal gravity. It thus removes the

Juan Maldacena

2011-01-01

251

Conformal Transformations and Space Travel  

Microsoft Academic Search

Conformal transformations are applied to the motion of a space ship experiencing a constant acceleration. The role of proper time is interpreted in terms of atomic periods, and the relationship between the conformal transformations and the general theory of relativity is clarified.

Suraj N. Gupta

1961-01-01

252

Counselor Identity: Conformity or Distinction?  

ERIC Educational Resources Information Center

|The authors explore 3 debates in other disciplines similar to counseling's identity debate in order to learn about common themes and outcomes. Conformity, distinction, and cohesion emerged as common themes. They conclude that counselors should retain their distinctive, humanistic approach rather than conforming to the dominant, medical approach.|

McLaughlin, Jerry E.; Boettcher, Kathryn

2009-01-01

253

The conformational locking of asparagine.  

PubMed

One dominant structure has been identified analysing the rotational spectrum of asparagine in sharp contrast with the multiconformational behaviour for other amino acids with polar side chains. This locking of the conformational variety to a single conformer has been ascribed to an intramolecular hydrogen bonding network involving ?-amine, ?-carboxylic and amide groups. PMID:22573205

Cabezas, Carlos; Varela, Marcelino; Peña, Isabel; Mata, Santiago; López, Juan C; Alonso, José L

2012-05-10

254

Conformational Dynamics of Actin: Effectors and Implications for Biological Function  

PubMed Central

Actin is a protein abundant in many cell types. Decades of investigations have provided evidence that it has many functions in living cells. The diverse morphology and dynamics of actin structures adapted to versatile cellular functions is established by a large repertoire of actin-binding proteins. The proper interactions with these proteins assume effective molecular adaptations from actin, in which its conformational transitions play essential role. This review attempts to summarise our current knowledge regarding the coupling between the conformational states of actin and its biological function.

Hild, Gabor; Bugyi, Beata; Nyitrai, Miklos

2010-01-01

255

Holographic Dual of a Boundary Conformal Field Theory  

SciTech Connect

We propose a holographic dual of a conformal field theory defined on a manifold with boundaries, i.e., boundary conformal field theory (BCFT). Our new holography, which may be called anti-de Sitter BCFT, successfully calculates the boundary entropy or g function in two-dimensional BCFTs and it agrees with the finite part of the holographic entanglement entropy. Moreover, we can naturally derive a holographic g theorem. We also analyze the holographic dual of an interval at finite temperature and show that there is a first order phase transition.

Takayanagi, Tadashi [Institute for the Physics and Mathematics of the Universe (IPMU), University of Tokyo, Kashiwa, Chiba 277-8582 (Japan)

2011-09-02

256

Holographic dual of a boundary conformal field theory.  

PubMed

We propose a holographic dual of a conformal field theory defined on a manifold with boundaries, i.e., boundary conformal field theory (BCFT). Our new holography, which may be called anti-de Sitter BCFT, successfully calculates the boundary entropy or g function in two-dimensional BCFTs and it agrees with the finite part of the holographic entanglement entropy. Moreover, we can naturally derive a holographic g theorem. We also analyze the holographic dual of an interval at finite temperature and show that there is a first order phase transition. PMID:21981491

Takayanagi, Tadashi

2011-08-30

257

Intrinsically disordered proteins and conformational noise: implications in cancer.  

PubMed

Intrinsically disordered proteins, IDPs, are proteins that lack a rigid 3D structure under physiological conditions, at least in vitro. Despite the lack of structure, IDPs play important roles in biological processes and transition from disorder to order upon binding to their targets. With multiple conformational states and rapid conformational dynamics, they engage in myriad and often "promiscuous" interactions. These stochastic interactions between IDPs and their partners, defined here as conformational noise, is an inherent characteristic of IDP interactions. The collective effect of conformational noise is an ensemble of protein network configurations, from which the most suitable can be explored in response to perturbations, conferring protein networks with remarkable flexibility and resilience. Moreover, the ubiquitous presence of IDPs as transcriptional factors and, more generally, as hubs in protein networks, is indicative of their role in propagation of transcriptional (genetic) noise. As effectors of transcriptional and conformational noise, IDPs rewire protein networks and unmask latent interactions in response to perturbations. Thus, noise-driven activation of latent pathways could underlie state-switching events such as cellular transformation in cancer. To test this hypothesis, we created a model of a protein network with the topological characteristics of a cancer protein network and tested its response to a perturbation in presence of IDP hubs and conformational noise. Because numerous IDPs are found to be epigenetic modifiers and chromatin remodelers, we hypothesize that they could further channel noise into stable, heritable genotypic changes. PMID:23255110

Mahmoudabadi, Gita; Rajagopalan, Krithika; Getzenberg, Robert H; Hannenhalli, Sridhar; Rangarajan, Govindan; Kulkarni, Prakash

2012-12-19

258

Conformational Dynamics of a Ligand-Free Adenylate Kinase  

PubMed Central

Adenylate kinase (AdK) is a phosphoryl-transfer enzyme with important physiological functions. Based on a ligand-free open structure and a ligand-bound closed structure solved by crystallography, here we use molecular dynamics simulations to examine the stability and dynamics of AdK conformations in the absence of ligands. We first perform multiple simulations starting from the open or the closed structure, and observe their free evolutions during a simulation time of 100 or 200 nanoseconds. In all seven simulations starting from the open structure, AdK remained stable near the initial conformation. The eight simulations initiated from the closed structure, in contrast, exhibited large variation in the subsequent evolutions, with most (seven) undergoing large-scale spontaneous conformational changes and approaching or reaching the open state. To characterize the thermodynamics of the transition, we propose and apply a new sampling method that employs a series of restrained simulations to calculate a one-dimensional free energy along a curved pathway in the high-dimensional conformational space. Our calculated free energy profile features a single minimum at the open conformation, and indicates that the closed state, with a high (?13 kcal/mol) free energy, is not metastable, consistent with the observed behaviors of the unrestrained simulations. Collectively, our simulations suggest that it is energetically unfavorable for the ligand-free AdK to access the closed conformation, and imply that ligand binding may precede the closure of the enzyme.

Song, Hyun Deok; Zhu, Fangqiang

2013-01-01

259

Conformational heterogeneity of creatine kinase determined from phase resolved fluorometry.  

PubMed Central

Fluorescence lifetimes of dimeric rabbit muscle creatine kinase specifically dansylated at both active sites and the homologous monomeric lobster muscle arginine kinase singly dansylated were determined using phase-modulation methods with global analysis of overdetermined data sets. For both proteins, the data is adequately described by three discrete exponential decays or a Lorentzian double distributed decay. Analogue phase resolved spectroscopy also reveals the presence of at least two distinct fluorophore domains for the dansyl moieties of creatine kinase. The model fluorophore, dansyllysine, exhibits a monoexponential decay with a value that is highly solvent dependent. Because the monomeric arginine kinase exhibits essentially the same decay law as doubly derivatized dimeric creatine kinase, it is proposed that the multiple lifetimes of creatine kinase reflect two or more isomeric dimeric states and not subunit asymmetry within a conformationally homogeneous dimeric population. Exposure of arginine kinase to 6 M guanidinium chloride results in a shift to shorter lifetimes and narrowing of the lifetime distributions. Creatine kinase displays a small narrowing of the distribution, but little change in fractional populations or lifetimes. These results suggest the presence of structural elements resistant to denaturation. The longest lifetime component in the triexponential discrete decay law of doubly dansylated creatine kinase is totally unquenched by acrylamide, whereas the two shorter lifetime components exhibit limited dynamic quenching. Steady-state quenching by acrylamide is significant and reveals a sharp distinction between accessible and non accessible dansyl groups. The major mechanism for interaction between the dansyl moieties and acrylamide is, atypically, static quenching. The results are consistent with two dansyl domains, one accessible and hydrophilic according to lifetime values and the other inaccessible and hydrophobic in solvent characteristics.Energy transfer between the dansyl group and the eight tryptophan residues of dimeric creatine kinase give similar results(~ 35%) from measurements of lifetimes, steady-state donor quenching and sensitized acceptor emission. The similarity suggests that the overall flexibility of the dimeric protein is limited. The occurrence of multiple conformers of muscle creatine kinase provides an explanation for several previous observations, most notably the structural origins for compartmentation of the muscle isozyme observed in the myofibril.

Grossman, S. H.

1991-01-01

260

Tracing conformational changes in proteins  

PubMed Central

Background Many proteins undergo extensive conformational changes as part of their functionality. Tracing these changes is important for understanding the way these proteins function. Traditional biophysics-based conformational search methods require a large number of calculations and are hard to apply to large-scale conformational motions. Results In this work we investigate the application of a robotics-inspired method, using backbone and limited side chain representation and a coarse grained energy function to trace large-scale conformational motions. We tested the algorithm on four well known medium to large proteins and we show that even with relatively little information we are able to trace low-energy conformational pathways efficiently. The conformational pathways produced by our methods can be further filtered and refined to produce more useful information on the way proteins function under physiological conditions. Conclusions The proposed method effectively captures large-scale conformational changes and produces pathways that are consistent with experimental data and other computational studies. The method represents an important first step towards a larger scale modeling of more complex biological systems.

2010-01-01

261

Towards conformal loop quantum gravity  

NASA Astrophysics Data System (ADS)

A discussion is given of recent developments in canonical gravity that assimilates the conformal analysis of gravitational degrees of freedom. The work is motivated by the problem of time in quantum gravity and is carried out at the metric and the triad levels. At the metric level, it is shown that by extending the Arnowitt-Deser-Misner (ADM) phase space of general relativity (GR), a conformal form of geometrodynamics can be constructed. In addition to the Hamiltonian and Diffeomorphism constraints, an extra first class constraint is introduced to generate conformal transformations. This phase space consists of York's mean extrinsic curvature time, conformal three-metric and their momenta. At the triad level, the phase space of GR is further enlarged by incorporating spin-gauge as well as conformal symmetries. This leads to a canonical formulation of GR using a new set of real spin connection variables. The resulting gravitational constraints are first class, consisting of the Hamiltonian constraint and the canonical generators for spin-gauge and conformorphism transformations. The formulation has a remarkable feature of being parameter-free. Indeed, it is shown that a conformal parameter of the Barbero-Immirzi type can be absorbed by the conformal symmetry of the extended phase space. This gives rise to an alternative approach to loop quantum gravity that addresses both the conceptual problem of time and the technical problem of functional calculus in quantum gravity.

H-T Wang, Charles

2006-03-01

262

Conformal tensors via Lovelock gravity  

NASA Astrophysics Data System (ADS)

Constructs from conformal geometry are important in low dimensional gravity models, while in higher dimensions the higher curvature interactions of Lovelock gravity are similarly prominent. Considering conformal invariance in the context of Lovelock gravity leads to natural, higher curvature generalizations of the Weyl, Schouten, Cotton and Bach tensors, with properties that straightforwardly extend those of their familiar counterparts. As a first application, we introduce a new set of conformally invariant gravity theories in D = 4k dimensions, based on the squares of the higher curvature Weyl tensors.

Kastor, David

2013-10-01

263

UV Raman Studies of Peptide Conformation Demonstrate That Betanova Does Not Cooperatively Unfold †  

Microsoft Academic Search

We used UV resonance Raman spectroscopy (UVRR) excited within the peptide bond ? f ?* electronic transitions and within the aromatic amino acid ? f ?* electronic transitions to examine the temperature dependence of the solution conformation of betanova, a 20-residue ? -sheet polypeptide (Kortemme, T., Ramirez-Alvarado, M., and Serrano, L. (1998) Science 281, 253-256). The 206.5 nm excited UVRR

Mary N. Boyden; Sanford A. Asher

2001-01-01

264

CONFORMANCE IMPROVEMENT USING GELS  

SciTech Connect

This technical progress report describes work performed from June 20 through December 19, 2001, for the project, ''Conformance Improvement Using Gels''. Interest has increased in some new polymeric products that purport to substantially reduce permeability to water while causing minimum permeability reduction to oil. In view of this interest, we are currently studying BJ's Aqua Con. Results from six corefloods revealed that the Aqua Con gelant consistently reduced permeability to water more than that to oil. However, the magnitude of the disproportionate permeability reduction varied significantly for the various experiments. Thus, as with most materials tested to date, the issue of reproducibility and control of the disproportionate permeability remains to be resolved. Concern exists about the ability of gels to resist washout after placement in fractures. We examined whether a width constriction in the middle of a fracture would cause different gel washout behavior upstream versus downstream of the constriction. Tests were performed using a formed Cr(III)-acetate-HPAM gel in a 48-in.-long fracture with three sections of equal length, but with widths of 0.08-, 0.02-, and 0.08-in., respectively. The pressure gradients during gel extrusion (i.e., placement) were similar in the two 0.08-in.-wide fracture sections, even though they were separated by a 0.02-in.-wide fracture section. The constriction associated with the middle fracture section may have inhibited gel washout during the first pulse of brine injection after gel placement. However, during subsequent phases of brine injection, the constriction did not inhibit washout in the upstream fracture section any more than in the downstream section.

Randall S. Seright

2002-02-28

265

Conformational analysis of flephedrone using quantum mechanical models.  

PubMed

Flephedrone is an analogue of cathinone - chemically similar to ephedrine, cathine and other amphetamines. Conformations of all isomers of flephedrone have been studied at the quantum-chemical level. Calculations have been performed using DFT and MP2 methods with two basis sets - 6-31G and 6-31G(d,p). Results show that there are low energy conformers for the ortho, meta, and para isomers that are connected by way of low-barrier transition states. Boltzmann distribution of population predicts the highest population for the 1-meta conformer with a 10% increase in solution. The molecular electrostatic potential surface data for each molecule has been calculated revealing likely reaction sites. PMID:23239394

Kolodziejczyk, Wojciech; Jodkowski, Jerzy; Holmes, Tiffani M; Hill, Glake A

2012-12-14

266

"Induced" N=4 conformal supergravity  

NASA Astrophysics Data System (ADS)

We consider an Abelian N=4 super Yang-Mills theory coupled to background N=4 conformal supergravity fields. At the classical level, this coupling is invariant under global SU(1,1) transformation of the complex ("dilaton-axion") supergravity scalar combined with an on-shell N=4 vector-vector duality. We compute the divergent part of the corresponding quantum effective action found by integrating over the super Yang-Mills fields and demonstrate its SU(1,1) invariance. This divergent part related to the conformal anomaly is one-loop exact and should be given by the N=4 conformal supergravity action containing the Weyl tensor squared term. This allows us to determine the full non-linear form of the bosonic part of the N=4 conformal supergravity action which has manifest SU(1,1) invariance.

Buchbinder, I. L.; Pletnev, N. G.; Tseytlin, A. A.

2012-10-01

267

Lattice simulations and infrared conformality  

NASA Astrophysics Data System (ADS)

We examine several recent lattice-simulation data sets, asking whether they are consistent with infrared conformality. We observe, in particular, that for an SU(3) gauge theory with 12 Dirac fermions in the fundamental representation, recent simulation data can be described assuming infrared conformality. Lattice simulations include a fermion mass m that is then extrapolated to zero, and we note that this data can be fit by a small-m expansion, allowing a controlled extrapolation. We also note that the conformal hypothesis does not work well for two theories that are known or expected to be confining and chirally broken, and that it does work well for another theory expected to be infrared conformal.

Appelquist, T.; Fleming, G. T.; Lin, M. F.; Neil, E. T.; Schaich, D. A.

2011-09-01

268

Polymer Conformation by Light Scattering.  

National Technical Information Service (NTIS)

In this project, we tried to study the conformation and dynamics of supramolecular solutions by developing the technique of laser light scattering and by examining the fluid behavior near the critical mixing point. We improved the technique of photon corr...

B. Chu

1979-01-01

269

Integrin structures and conformational signaling  

PubMed Central

Integrins are cell adhesion molecules that play critical roles in development, wound healing, hemostasis, immunity and cancer. Advances in the past two years have shed light on the structural basis for integrin regulation and signaling, especially on how global conformational changes between bent and extended conformations relate to the inter-domain and intra-domain shape shifting that regulates affinity for ligand. The downward movements of the C-terminal helices of the ? I and ? I domains and the swing-out of the hybrid domain play pivotal roles in integrin conformational signaling. Experiments have also shown that integrins transmit bidirectional signals across the plasma membrane by coupling extracellular conformational change with an unclasping and separation of the ? and ? transmembrane and cytoplasmic domains.

Luo, Bing-Hao; Springer, Timothy A

2006-01-01

270

Radial coordinates for conformal blocks  

NASA Astrophysics Data System (ADS)

We develop the theory of conformal blocks in CFTd expressing them as power series with Gegenbauer polynomial coefficients. Such series have a clear physical meaning when the conformal block is analyzed in radial quantization: individual terms describe contributions of descendants of a given spin. Convergence of these series can be optimized by a judicious choice of the radial quantization origin. We argue that the best choice is to insert the operators symmetrically. We analyze in detail the resulting “?-series” and show that it converges much more rapidly than for the commonly used variable z. We discuss how these conformal block representations can be used in the conformal bootstrap. In particular, we use them to derive analytically some bootstrap bounds whose existence was previously found numerically.

Hogervorst, Matthijs; Rychkov, Slava

2013-05-01

271

Stereoelectronic effects on polyproline conformation  

Microsoft Academic Search

The polyproline type II (PPII) helix is a prevalent conformation in both folded and unfolded proteins, and is known to play important roles in a wide variety of biological processes. Polyproline itself can also form a type I (PPI) helix, which has a disparate conformation. Here, we use derivatives of polyproline, (Pro)10, (Hyp)10, (Flp)10, and (flp)10, where Hyp is (2S,4R)-4-hydroxyproline,

JIA-CHERNG HORNG; RONALD T. RAINES

2006-01-01

272

CONFORMANCE IMPROVEMENT USING GELS  

SciTech Connect

This technical progress report describes work performed from September 1, 2003, through February 29, 2004, for the project, ''Conformance Improvement Using Gels.'' We examined the properties of several ''partially formed'' gels that were formulated with a combination of high and low molecular weight HPAM polymers. After placement in 4-mm-wide fractures, these gels required about 25 psi/ft for brine to breach the gel (the best performance to date in fractures this wide). After this breach, stabilized residual resistance factors decreased significantly with increased flow rate. Also, residual resistance factors were up to 9 times greater for water than for oil. Nevertheless, permeability reduction factors were substantial for both water and oil flow. Gel with 2.5% chopped fiberglass effectively plugged 4-mm-wide fractures if a 0.5-mm-wide constriction was present. The ability to screen-out at a constriction appears crucial for particulate incorporation to be useful in plugging fractures. In addition to fiberglass, we examined incorporation of polypropylene fibers into gels. Once dispersed in brine or gelant, the polypropylene fibers exhibited the least gravity segregation of any particulate that we have tested to date. In fractures with widths of at least 2 mm, 24-hr-old gels (0.5% high molecular weight HPAM) with 0.5% fiber did not exhibit progressive plugging during placement and showed extrusion pressure gradients similar to those of gels without the fiber. The presence of the fiber roughly doubled the gel's resistance to first breach by brine flow. The breaching pressure gradients were not as large as for gels made with high and low molecular weight polymers (mentioned above). However, their material requirements and costs (i.e., polymer and/or particulate concentrations) were substantially lower than for those gels. A partially formed gel made with 0.5% HPAM did not enter a 0.052-mm-wide fracture when applying a pressure gradient of 65 psi/ft. This result suggests a lower limit of fracture width for entry of formed or partially formed gels (when reasonable pressure gradients are applied). In unfractured porous rock, we investigated the time dependence of oil and water permeabilities during various cycles of oil and water injection after placement of a Cr(III)-acetate-HPAM gel. Permeability to water stabilized rapidly (within 1 pore volume, PV), while permeability to oil stabilized gradually over the course of 100 PV. The behavior was surprisingly insensitive to core material (strongly water-wet Berea sandstone and strongly oil-wet porous polyethylene), core permeability (740 to 10,000 md), and applied pressure gradient (10 to 100 psi/ft).

Randall S. Seright

2004-03-01

273

CONFORMANCE IMPROVEMENT USING GELS  

SciTech Connect

This report describes work performed during the third and final year of the project, ''Conformance Improvement Using Gels.'' Corefloods revealed throughput dependencies of permeability reduction by polymers and gels that were much more prolonged during oil flow than water flow. This behavior was explained using simple mobility ratio arguments. A model was developed that quantitatively fits the results and predicts ''clean up'' times for oil productivity when production wells are returned to service after application of a polymer or gel treatment. X-ray computed microtomography studies of gels in strongly water-wet Berea sandstone and strongly oil-wet porous polyethylene suggested that oil penetration through gel-filled pores occurs by a gel-dehydration mechanism, rather than gel-ripping or gel-displacement mechanisms. In contrast, analysis of data from the University of Kansas suggests that the gel-ripping or displacement mechanisms are more important in more permeable, strongly water-wet sandpacks. These findings help to explain why aqueous gels can reduce permeability to water more than to oil under different conditions. Since cement is the most commonly used material for water shutoff, we considered when gels are preferred over cements. Our analysis and experimental results indicated that cement cannot be expected to completely fill (top to bottom) a vertical fracture of any width, except near the wellbore. For vertical fractures with apertures less than 4 mm, the cement slurry will simply not penetrate very far into the fracture. For vertical fractures with apertures greater than 4 mm, the slurry may penetrate a substantial distance into the bottom part of the fracture. However, except near the wellbore, the upper part of the fracture will remain open due to gravity segregation. We compared various approaches to plugging fractures using gels, including (1) varying polymer content, (2) varying placement (extrusion) rate, (3) using partially formed gels, (4) using combinations of high and low molecular weight (Mw) polymers, (5) using secondary crosslinking reactions, (6) injecting un-hydrated polymer particles, and (7) incorporating particulates. All of these methods showed promise in some aspects, but required performance improvements in other aspects. All materials investigated to date showed significant performance variations with fracture width. High pressure gradients and limited distance of penetration are common problems in tight fractures. Gravity segregation and low resistance to breaching are common problems in wide fractures. These will be key issues to address in future work. Although gels can exhibit disproportionate permeability reduction in fractures, the levels of permeability reduction for oil flow are too high to allow practical exploitation in most circumstances. In contrast, disproportionate permeability reduction provided by gels that form in porous rock (adjacent to the fractures) has considerable potential in fractured systems.

Randall S. Seright

2004-09-30

274

Protein-dependent conformational behavior of DNA in chromatin  

SciTech Connect

Information from circular dichroism (CD) and DNA thermal denaturation has been used in concert to study the conformation behavior of DNA in the extended 11-nm fiber of chromatin isolated from HeLa nuclei. The histone-dependent conformational states of the system were investigated by selectively removing the hydrophilic histone domains with trypsin. These were compared to acetylated chromatin from the same source. The integrated intensity of the positive CD band for DNA above 260 nm is found to increase with the content of relatively unstressed B-form DNA. This same increase is observed along the series of whole, H1-stripped, and trypsinized chromatin samples as protein is removed. Hence, the ratio of percent hyperchromicity to integrated CD band intensity of the respective melting transitions provides useful information on the conformational state of DNA in the three principal regions of the chromatin fiber: the central loop and flanking nucleosomal regions and the linker. Results from this study suggest that central loop DNA in both hyperacetylated and control chromatin relaxes as protein is removed. However, hyperacetylated chromatin shows significantly less dependence than control chromatin upon core histone hydrophilic domains in the flanking and linker regions. Thus, histone hyperacetylation evidently relaxes DNA in chromatin with no major overall conformational changes. A possible role of histone hyperacetylation may therefore be to reduce cooperativity in the unfolding transition in chromatin and thus provide for greater localized control of unfolding during transcription.

Riehm, M.R.; Harrington, R.E.

1987-05-19

275

Conformational changes couple Na+ and glucose transport.  

PubMed

The mechanism by which cotransport proteins couple their substrates across cell membranes is not known. A commonly proposed model is that cotransport results from ligand-induced conformational transitions that change the accessibility of ligand-binding sites from one side of the membrane to the other. To test this model, we have measured the accessibility of covalent probes to a cysteine residue (Q457C) placed in the putative sugar-translocation domain of the Na+/glucose cotransporter (SGLT1). The mutant protein Q457C was able to transport sugar, but transport was abolished after alkylation by methanethiosulfonate reagents. Alkylation blocked sugar translocation but not sugar binding. Accessibility of Q457C to alkylating reagents required external Na+ and was blocked by external sugar and phlorizin. The voltage dependence of accessibility was directly correlated with the presteady-state charge movement of SGLT1. Voltage-jump experiments with rhodamine-6-maleimide-labeled Q457C showed that the time course and level of changes in fluorescence closely followed the presteady-state charge movement. We conclude that conformational changes are responsible for the coupling of Na+ and sugar transport and that Q457 plays a critical role in sugar translocation by SGLT1. PMID:9636229

Loo, D D; Hirayama, B A; Gallardo, E M; Lam, J T; Turk, E; Wright, E M

1998-06-23

276

Conformational changes couple Na+ and glucose transport  

PubMed Central

The mechanism by which cotransport proteins couple their substrates across cell membranes is not known. A commonly proposed model is that cotransport results from ligand-induced conformational transitions that change the accessibility of ligand-binding sites from one side of the membrane to the other. To test this model, we have measured the accessibility of covalent probes to a cysteine residue (Q457C) placed in the putative sugar-translocation domain of the Na+/glucose cotransporter (SGLT1). The mutant protein Q457C was able to transport sugar, but transport was abolished after alkylation by methanethiosulfonate reagents. Alkylation blocked sugar translocation but not sugar binding. Accessibility of Q457C to alkylating reagents required external Na+ and was blocked by external sugar and phlorizin. The voltage dependence of accessibility was directly correlated with the presteady–state charge movement of SGLT1. Voltage-jump experiments with rhodamine-6-maleimide-labeled Q457C showed that the time course and level of changes in fluorescence closely followed the presteady–state charge movement. We conclude that conformational changes are responsible for the coupling of Na+ and sugar transport and that Q457 plays a critical role in sugar translocation by SGLT1.

Loo, Donald D. F.; Hirayama, Bruce A.; Gallardo, Elsa M.; Lam, Jason T.; Turk, Eric; Wright, Ernest M.

1998-01-01

277

A Physical Picture of Protein Dynamics and Conformational Changes  

Microsoft Academic Search

A physical model is reviewed which explains different aspects of protein dynamics consistently. At low temperatures, the molecules\\u000a are frozen in conformational substates. Their average energy is 3\\/2RT. Solid-state vibrations occur on a time scale of femtoseconds to nanoseconds. Above a characteristic temperature, often\\u000a called the dynamical transition temperature, slow modes of motions can be observed occurring on a time

Fritz G. Parak; Klaus Achterhold; Simonetta Croci; Marius Schmidt

2007-01-01

278

The role of PII conformations in the calculation of peptide fractional helix content.  

PubMed Central

Changes in the temperature, pH, ionic strength, or denaturant concentration of aqueous solutions of the monomeric non-alpha-helical peptide acetylYEAAAKEAPAKEAAAKAamide generate changes in its dichroic spectrum characteristic for a conformational transition. This transition has the characteristic features of a residue PII/unstructured conformational equilibrium in which PII denotes an extended left-handed helical conformation and unstructured denotes all the remaining conformations in a random coil ensemble. Replacement of the proline residue facilitates population of residues in an alpha-helical conformation. However, the ellipticity values for these non-proline peptides merge with the ellipticity of the proline peptide as the population of residues in the alpha-helix conformation is diminished. This convergence suggests that all residues in a host/guest peptide series of the same length share a common PII/unstructured conformational equilibrium in a given solvent. We propose that the fractional helix content of peptides within such a series may be estimated by using a two-state calculation in which the ellipticity for the non-alpha-helix conformations is provided by a peptide having a central proline guest residue.

Park, S. H.; Shalongo, W.; Stellwagen, E.

1997-01-01

279

Conformational analysis of cis-? 1, -? 2, -? 3 and -? 4-tetrahydrophthalic anhydrides by semiempirical and ab initio molecular orbital calculations  

Microsoft Academic Search

Semiempirical and ab initio molecular orbital calculations have been used to study the conformational geometries and the relative stability of the conformers of cis-?1, -?2, -?3 and -?4-tetrahydrophthalic anhydrides (THPA). The total energy and the structure of the transition states for the interconversion of conformers were calculated with PM3 semiempirical method. It is found that PM3, AM1 and MNDO semiempirical

A. Ben Fredj; S. Ben Rejeb; Z. Ben Lakhdar

2000-01-01

280

4-Methylpseudoproline derived from ?-methylserine - synthesis and conformational studies.  

PubMed

This paper presents the synthesis and solution conformational studies of the tripeptides Fmoc-Ala-(R)-(?Me)Ser(?(H,H)Pro)-Ala-OBu(t) (6a) and Fmoc-Ala-(S)-(?Me)Ser(?(H,H)Pro)-Ala-OBu(t) (6b). Additionally, the X-ray structure of 6a is given. NMR analysis corroborated by theoretical calculations (XPLOR) shows that in both peptides the amide bond between pseudoproline and the preceding amino acid is in the trans conformation. The same amide bond geometry was observed in the crystal state of 6a. The latter is additionally influenced by the presence of two symmetrically independent molecules in an asymmetric unit. Both molecules adopt a conformation which resembles ?-turn type II, stabilized by hydrogen bonding. The conformational preferences and prolyl cis-trans isomerization of Ac-(?Me)Ser(?(H,H)Pro)-NHMe (7) were explored at the IEFPCM/B3LYP/6-31+G(d) level of theory in vacuum, water and chloroform. It has been shown that the trans isomer predominates in water solutions and the cis isomer is preferred in chloroform. The conformation of 7 is down-puckered independently of the geometry of the amide bonds, with lower puckering in the transition state of the cis-trans isomerization. PMID:22806447

Katarzy?ska, Joanna; Mazur, Adam; Wolf, Wojciech M; Teat, Simon J; Jankowski, Stefan; Leplawy, Miros?aw T; Zabrocki, Janusz

2012-07-17

281

Solvation and conformational dynamics of dicarboxylic suberic acid  

NASA Astrophysics Data System (ADS)

Solvation structure and conformational preferences of the dicarboxylic suberic acid, HOOC(CH2)6COOH, both neutral and protolyzed in water and neutral in methanol have been studied using molecular-dynamics (MO) computer simulations. According to results from MD simulations in water solution, the backbone hydrocarbon chain shows a very clear tendency to curl up into a helical structure, forming either a tgggt or a tg'g'g't conformation. The carboxylic head groups are strongly hydrated in the water solution, while the hydrophobic hydrocarbon skeleton is surrounded by water molecules in a packed structure. In the helical conformation, the surface area of the nonpolar part of the fatty acid is minimized against water phase. Transitions between the right and the left-handed helices are observed in neutral and mono-anionic forms of suberic acid in water solution. Suberic acid dissolved in methanol does not show any conformational preferences. Along the hydrocarbon chain, g, g', and t conformers are equally populated. The head group torsional angles, however, strongly prefer trans conformation due to dipolar interactions between the carboxyl groups and the solvent hydroxyl groups. In addition to MD simulations, corresponding water and methanol solutions are prepared and 13C NMR (nuclear magnetic resonance) chemical shifts are measured in both solutions. Using a time-averaged geometry for suberic acid from MD simulations in water, chemical shielding constants are calculated quantum chemically. Agreement between the theoretical and the experimental chemical shifts is good, and gives indirect support to the simulated conformations of suberic acid in the investigated solutions. The simulation results are also consistent with recent Raman investigations of suberic acid in both water and methanol solutions.

Nilsson, J. Arvid; Laaksonen, A.; Eriksson, Leif A.

1998-08-01

282

Conformational analyses of the reaction coordinate of glycosidases.  

PubMed

The enzymatic hydrolysis of the glycosidic bond is catalyzed by diverse enzymes generically termed glycoside hydrolases (hereafter GHs) or glycosidases. The many sequence-based families of glycosidases have served as a rich hunting ground for enzymologists for years. Not only are these enzymes of fundamental interest, providing paradigms for enzymatic catalysis that extend beyond the bounds of carbohydrate chemistry, but the enzymes themselves play myriad essential roles in diverse biological processes. The wide utility of glycosidases, from their industrial harnessing in the hydrolysis of plant biomass to their roles in human physiology and disease, has engendered a large scientific constituency with an interest in glycosidase chemistry. A fascinating thread of this research, and one with major impact on the design of enzyme inhibitors, is the conformational analysis of reaction pathways within the diverse families. These GH families provide a large pallet of enzymes with which chemists have attempted to depict the conformational landscape of glycosidase action. In this Account, we review three-dimensional insight into the conformational changes directed by glycosidases, primarily from structural observations of the stable enzyme-ligand species adjacent to the transition state (or states) and of enzyme-inhibitor complexes. We further show how recent computational advances dovetail with structural insight to provide a quantum mechanical basis for glycosidase action. The glycosidase-mediated hydrolysis of the acetal or ketal bond in a glycoside may occur with either inversion or retention of the configuration of the anomeric carbon. Inversion involves a single step and transition state, whereas retention, often referred to as the double displacement, is a two-step process with two transition states. The single transition state for the inverting enzymes and the two transition states (those flanking the covalent intermediate) in the double displacement have been shown to have substantial oxocarbenium ion character. The dissociative nature of these transition states results in significant relative positive charge accumulation on the pyranose ring. The delocalization of lone-pair electrons from the ring oxygen that stabilizes the cationic transition state implies that at, or close to, the transition states the pyranose will be distorted away from its lowest energy conformation to one that favors orbital overlap. Over the preceding decade, research has highlighted the harnessing of noncovalent interactions to aid this distortion of the sugar substrates from their lowest energy chair conformation to a variety of different boat, skew boat, and half-chair forms, each of which favors catalysis with a given enzyme and substrate. Crystallographic observation of stable species that flank the transition state (or states), of both retaining and inverting glycosidases, has allowed a description of their conformational itineraries, illustrating how enzymes facilitate the "electrophilic migration" of the anomeric center along the reaction coordinate. The blossoming of computational approaches, such as ab initio metadynamics, has underscored the quantum mechanical basis for glycoside hydrolysis. Conformational analyses highlight not only the itineraries used by enzymes, enabling their inhibition, but are also reflected in the nonenzymatic synthesis of glycosides, wherein chemists mimic strategies found in nature. PMID:21923088

Davies, Gideon J; Planas, Antoni; Rovira, Carme

2011-09-16

283

Conformational transition in DNA on a cold surface  

Microsoft Academic Search

The contour length of DNA fragments, deposited and imaged on mica under buffer, was measured as a function of deposition temperature. Extended DNA molecules (on Ni- and silane-treated surfaces) contract rapidly with falling temperature, approaching the contour length of A-DNA at 2° ° ° °C. The contraction is not unique to a specific sequence and does not occur in solution

X. Z. Feng; R. Bash; P. Balagurumoorthy; D. Lohr; R. E. Harrington; S. M. Lindsay

2000-01-01

284

Disabilities & Transitions.  

ERIC Educational Resources Information Center

This newsletter discusses transition and outcome issues for young children with disabilities. Topics discussed include issues related to transition program administration, staff, families, and services. (KB)

Wolery, Mark

1998-01-01

285

Analysis of the stability of looped-out and stacked-in conformations of an adenine bulge in DNA using a continuum model for solvent and ions.  

PubMed

A combination of conformational search, energy minimization, and energetic evaluation using a continuum solvent treatment has been employed to study the stability of various conformations of the DNA fragment d(CGCAGAA)/d(TTCGCG) containing a single adenine bulge. The extra-helical (looped-out) bulge conformation derived from a published x-ray structure and intra-helical (stacked bulge base) model structures partially based on nuclear magnetic resonance (NMR) data were used as start structures for the conformational search. Solvent-dependent contributions to the stability of the conformations were calculated from the solvent exposed molecular surface area and by using the finite difference Poisson-Boltzmann approach. Three classes (I-III) of bulge conformations with calculated low energies can be distinguished. The lowest-energy conformations were found in class I, corresponding to structures with the bulge base stacked between flanking helices, and class II, composed of structures forming a triplet of the bulge base and a flanking base pair. All extra-helical bulge structures, forming class III, were found to be less stable compared with the lowest energy structures of class I and II. The results are consistent with NMR data on an adenine bulge in the same sequence context indicating an intra-helical or triplet bulge conformation in solution. Although the total energies and total electrostatic energies of the low-energy conformations show only relatively modest variations, the energetic contributions to the stability were found to vary significantly among the classes of bulge structures. All intra-helical bulge structures are stabilized by a more favorable Coulomb charge-charge interaction but destabilized by a larger electrostatic reaction field contribution compared with all extra-helical and most triplet bulge structures. Van der Waals packing interactions and nonpolar surface-area-dependent contributions appear to favor triplet class II structures and to a lesser degree also the intra-helical stacked bulge conformations. The large conformational variation found for class III conformers might add a favorable entropic contribution to the stability of the extra-helical bulge form. PMID:9414214

Zacharias, M; Sklenar, H

1997-12-01

286

CONFORMANCE IMPROVEMENT USING GELS  

SciTech Connect

This report describes work performed during the second year of the project, ''Conformance Improvement Using Gels.'' The project has two objectives. The first objective is to identify gel compositions and conditions that substantially reduce flow through fractures that allow direct channeling between wells, while leaving secondary fractures open so that high fluid injection and production rates can be maintained. The second objective is to optimize treatments in fractured production wells, where the gel must reduce permeability to water much more than that to oil. Pore-level images from X-ray computed microtomography were re-examined for Berea sandstone and porous polyethylene. This analysis suggests that oil penetration through gel-filled pores occurs by a gel-dehydration mechanism, rather than a gel-ripping mechanism. This finding helps to explain why aqueous gels can reduce permeability to water more than to oil. We analyzed a Cr(III)-acetate-HPAM gel treatment in a production well in the Arbuckle formation. The availability of accurate pressure data before, during, and after the treatment was critical for the analysis. After the gel treatment, water productivity was fairly constant at about 20% of the pre-treatment value. However, oil productivity was stimulated by a factor of 18 immediately after the treatment. During the six months after the treatment, oil productivity gradually decreased to approach the pre-treatment value. To explain this behavior, we proposed that the fracture area open to oil flow was increased substantially by the gel treatment, followed by a gradual closing of the fractures during subsequent production. For a conventional Cr(III)-acetate-HPAM gel, the delay between gelant preparation and injection into a fracture impacts the placement, leakoff, and permeability reduction behavior. Formulations placed as partially formed gels showed relatively low pressure gradients during placement, and yet substantially reduced the flow capacity of fractures (with widths from 1 to 4 mm) during brine and oil flow after placement. Regardless of gel age before placement, very little gel washed out from the fractures during brine or oil flow. However, increased brine or oil flow rate and cyclic injection of oil and water significantly decreased the level of permeability reduction. A particular need exists for gels that can plug large apertures (e.g., wide fractures and vugs). Improved mechanical strength and stability were demonstrated (in 1- to 4-mm-wide fractures) for a gel that contained a combination of high- and low-molecular weight polymers. This gel reduced the flow capacity of 2- and 4-mm-wide fractures by 260,000. In a 1-mm-wide fracture, it withstood 26 psi/ft without allowing any brine flow through the fracture. Cr(III)-acetate-HPAM gels exhibited disproportionate permeability reduction in fractures. The effect was most pronounced when the gel was placed as gelant or partially formed gels. The effect occurred to a modest extent with concentrated gels and with gels that were ''fully formed'' when placed. The effect was not evident in tubes. We explored swelling polymers for plugging fractures. Polymer suspensions were quickly prepared and injected. In concept, the partially dissolved polymer would lodge and swell to plug the fracture. For three types of swelling polymers, behavior was promising. However, additional development is needed before their performance will be superior to that of conventional gels.

Randall S. Seright

2003-09-01

287

Exploring the conformational and biological versatility of ?-turn-modified gramicidin S by using sugar amino acid homologues that vary in ring size.  

PubMed

Monobenzylated sugar amino acids (SAAs) that differ in ether ring size (containing an oxetane, furanoid, and pyranoid ring) were synthesized and incorporated in one of the ?-turn regions of the cyclo-decapeptide gramicidin S (GS). CD, NMR spectroscopy, modeling, and X-ray diffraction reveal that the ring size of the incorporated SAA moieties determines the spatial positioning of their cis-oriented carboxyl and aminomethyl substituents, thereby subtly influencing the amide linkages with the adjacent amino acids in the sequence. Unlike GS itself, the conformational behavior of the SAA-containing peptides is solvent dependent. The derivative containing the pyranoid SAA is slightly less hydrophobic and displays a diminished haemolytic activity, but has similar antimicrobial properties as GS. PMID:21365698

Knijnenburg, Annemiek D; Tuin, Adriaan W; Spalburg, Emile; de Neeling, Albert J; Mars-Groenendijk, Roos H; Noort, Daan; Otero, José M; Llamas-Saiz, Antonio L; van Raaij, Mark J; van der Marel, Gijs A; Overkleeft, Herman S; Overhand, Mark

2011-03-01

288

Conformal subalgebras of Kac-Moody algebras  

SciTech Connect

We define a conformal subalgebra of a Kac-Moody algebra as a subalgebra which has the same Sugawara conformal generator as the algebra in which it is embedded. This guarantees the preservation of conformal invariance, for instance, in the recently proposed construction of bosonic strings with nonsimply laced gauge groups. We present a complete list of all such conformal subalgebras.

Schellekens, A.N.; Warner, N.P.

1986-11-15

289

Cyclic AMP Analog Blocks Kinase Activation by Stabilizing Inactive Conformation: Conformational Selection Highlights a New Concept in Allosteric Inhibitor Design*  

PubMed Central

The regulatory (R) subunit of protein kinase A serves to modulate the activity of protein kinase A in a cAMP-dependent manner and exists in two distinct and structurally dissimilar, end point cAMP-bound “B” and C-subunit-bound “H”-conformations. Here we report mechanistic details of cAMP action as yet unknown through a unique approach combining x-ray crystallography with structural proteomics approaches, amide hydrogen/deuterium exchange and ion mobility mass spectrometry, applied to the study of a stereospecific cAMP phosphorothioate analog and antagonist((Rp)-cAMPS). X-ray crystallography shows cAMP-bound R-subunit in the B form but surprisingly the antagonist Rp-cAMPS-bound R-subunit crystallized in the H conformation, which was previously assumed to be induced only by C-subunit-binding. Apo R-subunit crystallized in the B form as well but amide exchange mass spectrometry showed large differences between apo, agonist and antagonist-bound states of the R-subunit. Further ion mobility reveals the apo R-subunit as an ensemble of multiple conformations with collisional cross-sectional areas spanning both the agonist and antagonist-bound states. Thus contrary to earlier studies that explained the basis for cAMP action through “induced fit” alone, we report evidence for conformational selection, where the ligand-free apo form of the R-subunit exists as an ensemble of both B and H conformations. Although cAMP preferentially binds the B conformation, Rp-cAMPS interestingly binds the H conformation. This reveals the unique importance of the equatorial oxygen of the cyclic phosphate in mediating conformational transitions from H to B forms highlighting a novel approach for rational structure-based drug design. Ideal inhibitors such as Rp-cAMPS are those that preferentially “select” inactive conformations of target proteins by satisfying all “binding” constraints alone without inducing conformational changes necessary for activation.

Badireddy, Suguna; Yunfeng, Gao; Ritchie, Mark; Akamine, Pearl; Wu, Jian; Kim, Choel W.; Taylor, Susan S.; Qingsong, Lin; Swaminathan, Kunchithapadam; Anand, Ganesh S.

2011-01-01

290

A Threaded Loop Conformation Adopted by a Family of Peptoid Nonamers  

PubMed Central

Non-natural polymers with well-defined three-dimensional folds offer considerable potential for engineering novel functions that are outside the scope of biological polymers. Here we describe a family of N-substituted glycine or ‘peptoid’ nonamers that folds into an unusual ‘threaded loop’ structure of exceptional thermal stability and conformational homogeneity in acetonitrile. The structure is chain length-specific and relies on bulky, chiral side chains and chain-terminating functional groups for stability. Notable elements of the structure include the engagement of the positively charged amino-terminus by carbonyl groups of the backbone through hydrogen bonding interactions, and shielding of polar groups from and near-complete exposure of hydrophobic groups to solvent, in a manner resembling a folded polypeptide globular domain turned ‘inside-out’. The structure is stable in a variety of organic solvents but is readily denatured in any solvent/cosolvent milieu with hydrogen bonding potential. The structure could serve as a scaffold for the elaboration of novel functions and could be used to test methodologies for predicting solvent-dependent polymer folding.

Huang, Kai; Wu, Cindy W.; Sanborn, Tracy J.; Patch, James A.; Kirshenbaum, Kent; Zuckermann, Ronald N.; Barron, Annelise E.; Radhakrishnan, Ishwar

2008-01-01

291

Dynamics of the quaternary conformational change in trout hemoglobin.  

PubMed

The kinetics of conformational changes in trout hemoglobin I have been characterized over the temperature range 2-65 degrees C from time-resolved absorption spectra measured following photodissociation of the carbon monoxide complex. Changes in the spectra of the deoxyheme photoproduct were used to monitor changes in the protein conformation. Although the deoxyheme spectral changes are only about 8% of the total spectral change due to ligand rebinding, a combination of high-precision measurements and singular value decomposition of the data permits a detailed analysis of both their amplitudes and relaxation rates. Systematic variation of the degree of photolysis was used to alter the distribution of liganded tetramers, permitting the assignment of the spectral relaxation at 20 microseconds to the R----T quaternary conformational change of the zero-liganded and singly liganded molecules and spectral relaxations at about 50 ns and 2 microseconds to tertiary conformational changes within the R structure. Analysis of the effect of photoselection by the linearly polarized excitation pulse indicates that a major contribution to the apparent geminate rebinding in the 50-ns relaxation arises from rotational diffusion of molecules containing unphotolyzed heme-CO complexes. The activation enthalpy and activation entropy for the R0----T0 transition are +7.4 kcal/mol and -12 cal mol-1 K-1. Using the equilibrium data, delta H = +29.4 kcal/mol and delta S = +84.4 cal mol-1 K-1 [Barisas, B. G., & Gill, S. J. (1979) Biophys. Chem. 9, 235-244], the activation parameters for the T0----R0 transition are calculated to be delta H = +37 kcal/mol and delta S = +73 cal mol-1 K-1. The similarity of the equilibrium and activation parameters for the T0----R0 transition indicates that the transition state is much more R-like than T-like. This result suggests that in the path from T0 to R0 the subunits have already almost completely rearranged into the R configuration when the transition state is reached, while in the path from R0 to T0 the subunits remain in a configuration close to R in the transition state. The finding of an R-like transition state explains why the binding of ligands causes much smaller changes in the R----T rates than in the T----R rates. PMID:2054357

Hofrichter, J; Henry, E R; Szabo, A; Murray, L P; Ansari, A; Jones, C M; Coletta, M; Falcioni, G; Brunori, M; Eaton, W A

1991-07-01

292

Conformational dynamics and thermodynamics of protein-ligand binding studied by NMR relaxation.  

PubMed

Protein conformational dynamics can be critical for ligand binding in two ways that relate to kinetics and thermodynamics respectively. First, conformational transitions between different substates can control access to the binding site (kinetics). Secondly, differences between free and ligand-bound states in their conformational fluctuations contribute to the entropy of ligand binding (thermodynamics). In the present paper, I focus on the second topic, summarizing our recent results on the role of conformational entropy in ligand binding to Gal3C (the carbohydrate-recognition domain of galectin-3). NMR relaxation experiments provide a unique probe of conformational entropy by characterizing bond-vector fluctuations at atomic resolution. By monitoring differences between the free and ligand-bound states in their backbone and side chain order parameters, we have estimated the contributions from conformational entropy to the free energy of binding. Overall, the conformational entropy of Gal3C increases upon ligand binding, thereby contributing favourably to the binding affinity. Comparisons with the results from isothermal titration calorimetry indicate that the conformational entropy is comparable in magnitude to the enthalpy of binding. Furthermore, there are significant differences in the dynamic response to binding of different ligands, despite the fact that the protein structure is virtually identical in the different protein-ligand complexes. Thus both affinity and specificity of ligand binding to Gal3C appear to depend in part on subtle differences in the conformational fluctuations that reflect the complex interplay between structure, dynamics and ligand interactions. PMID:22435823

Akke, Mikael

2012-04-01

293

Polyethylene glycol binding alters human telomere G-quadruplex structure by conformational selection.  

PubMed

Polyethylene glycols (PEGs) are widely used to perturb the conformations of nucleic acids, including G-quadruplexes. The mechanism by which PEG alters G-quadruplex conformation is poorly understood. We describe here studies designed to determine how PEG and other co-solutes affect the conformation of the human telomeric quadruplex. Osmotic stress studies using acetonitrile and ethylene glycol show that conversion of the 'hybrid' conformation to an all-parallel 'propeller' conformation is accompanied by the release of about 17 water molecules per quadruplex and is energetically unfavorable in pure aqueous solutions. Sedimentation velocity experiments show that the propeller form is hydrodynamically larger than hybrid forms, ruling out a crowding mechanism for the conversion by PEG. PEGs do not alter water activity sufficiently to perturb quadruplex hydration by osmotic stress. PEG titration experiments are most consistent with a conformational selection mechanism in which PEG binds more strongly to the propeller conformation, and binding is coupled to the conformational transition between forms. Molecular dynamics simulations show that PEG binding to the propeller form is sterically feasible and energetically favorable. We conclude that PEG does not act by crowding and is a poor mimic of the intranuclear environment, keeping open the question of the physiologically relevant quadruplex conformation. PMID:23804761

Buscaglia, Robert; Miller, M Clarke; Dean, William L; Gray, Robert D; Lane, Andrew N; Trent, John O; Chaires, Jonathan B

2013-06-26

294

Polyethylene glycol binding alters human telomere G-quadruplex structure by conformational selection  

PubMed Central

Polyethylene glycols (PEGs) are widely used to perturb the conformations of nucleic acids, including G-quadruplexes. The mechanism by which PEG alters G-quadruplex conformation is poorly understood. We describe here studies designed to determine how PEG and other co-solutes affect the conformation of the human telomeric quadruplex. Osmotic stress studies using acetonitrile and ethylene glycol show that conversion of the ‘hybrid’ conformation to an all-parallel ‘propeller’ conformation is accompanied by the release of about 17 water molecules per quadruplex and is energetically unfavorable in pure aqueous solutions. Sedimentation velocity experiments show that the propeller form is hydrodynamically larger than hybrid forms, ruling out a crowding mechanism for the conversion by PEG. PEGs do not alter water activity sufficiently to perturb quadruplex hydration by osmotic stress. PEG titration experiments are most consistent with a conformational selection mechanism in which PEG binds more strongly to the propeller conformation, and binding is coupled to the conformational transition between forms. Molecular dynamics simulations show that PEG binding to the propeller form is sterically feasible and energetically favorable. We conclude that PEG does not act by crowding and is a poor mimic of the intranuclear environment, keeping open the question of the physiologically relevant quadruplex conformation.

Buscaglia, Robert; Miller, M. Clarke; Dean, William L.; Gray, Robert D.; Lane, Andrew N.; Trent, John O.; Chaires, Jonathan B.

2013-01-01

295

Conformal theories and punctured surfaces  

NASA Astrophysics Data System (ADS)

We define conformal theories as realizations of certain operations involving punctured Riemann surfaces (with coordinates chosen at the punctures) in a Hilbert space. We describe the connections of our formalism with other formulations of conformal theories. We would like to thank D. Kazhdan and G. Moore for many interesting discussions in connection with this work. We would also like to thank our collaborators in ref. [10] for the joint work which motivated this formulation of conformal theories and also J. Harer and R.C. Penner for sending us some of their work on the structure of moduli space. We have also benefited from discussions with J. Bernstein, J. Distler, J. Harris, C. Hodgson, A. LeClair, J. Morgan and P. Nelson. This research was supported in part by NSF contract PHY-82-15249, and by a fellowship from the Harvard Society of Fellows.

Vafa, Cumrun

1987-12-01

296

Transit Tracks  

NSDL National Science Digital Library

In this space science activity, learners explore transits and the conditions when a transit may be seen. Learners use models to investigate how a planet's size and distance from its star affects the behavior of transits. Learners also use mathematics to interpret graphs of brightness vs. time to deduce information about planet-star systems. This lesson includes educator instructions, photocopy masters for Transit Light Curves, Option Math for Transit Tracks, Keplerâs 3rd Law graphs, cube root tables, an account of Jeremiah Horrocks' 1639 observation of the transit of Venus, and an answer key for the Transit Tracks Light Curves.

Science, Lawrence H.

2008-01-01

297

Conformal deposition of LPCVD TEOS  

NASA Astrophysics Data System (ADS)

The step coverage of dielectrics is important for the microelectronics industry and critical to Micro-machined products and High Voltage MEMS drivers. The techniques used to fabricate MEMS structures require void free refill processes and even film deposition along deep trenches to protect against etch chemistries. High voltage drivers used to actuate MEMS devices benefit from dielectric isolation, which reduces the need for large tub formation between devices. It also enables 'system on chip' solutions for MEMs devices and protection against voltage spikes. This paper presents a process developed at Analog Devices Belfast that enables an LPCVD TEOS furnace to perform a highly conformal trench refill without equipment modification. The conformality is over 95% for 20 micrometer deep trenches and maintains a conformality greater than 85% in 50 micrometer deep trenches. This compares with 75% conformality which is considered excellent for 20 micrometer trench refills obtained using previous LPCVD TEOS processing. The process is shown to have benefits in conformality, breakdown voltage, and stress over standard trench fill processes including Ozone TEOS. The densification of the TEOS film has been optimized for electrical parameters using CV and IV techniques, while XPS, FTIR and spectroscopic ellipsometry are used for physical characterization. Stress is a very important parameter for micro-machining and the conformal TEOS has a film stress which is tensile 30 - 40 MPa as deposited and compressive 100 MPa after densification. The breakdown voltage has been measured at 8.5 MV/cm compared to 7.5 - 9 MV/cm for a typical densified TEOS film and the refractive index is 1.456 compared to 1.465 for a thermal oxide. Analog Devices Belfast is part of the Micro-machined Products division and provides SOI and customized SOI for the MEMs and IC market.

McCann, Paul; Somasundram, Kumar; Byrne, Stephen; Nevin, Andy

2001-09-01

298

Social influence: compliance and conformity.  

PubMed

This review covers recent developments in the social influence literature, focusing primarily on compliance and conformity research published between 1997 and 2002. The principles and processes underlying a target's susceptibility to outside influences are considered in light of three goals fundamental to rewarding human functioning. Specifically, targets are motivated to form accurate perceptions of reality and react accordingly, to develop and preserve meaningful social relationships, and to maintain a favorable self-concept. Consistent with the current movement in compliance and conformity research, this review emphasizes the ways in which these goals interact with external forces to engender social influence processes that are subtle, indirect, and outside of awareness. PMID:14744228

Cialdini, Robert B; Goldstein, Noah J

2004-01-01

299

SUSY Unparticle and Conformal Sequestering  

SciTech Connect

We investigate unparticle physics with supersymmetry (SUSY). The SUSY breaking effects due to the gravity mediation induce soft masses for the SUSY unparticles and hence break the conformal invariance. The unparticle physics observable in near future experiments is only consistent if the SUSY breakingeffects from the hidden sector to the standard model sector are dominated by the gauge mediation, or if the SUSY breaking effects to the unparticle sector are sufficiently sequestered. We argue that the natural realization of the latter possibility is the conformal sequestering scenario.

Nakayama, Yu; Nakayama, Yu

2007-07-17

300

Enzymatic detoxication, conformational selection, and the role of molten globule active sites.  

PubMed

The role of conformational ensembles in enzymatic reactions remains unclear. Discussion concerning "induced fit" versus "conformational selection" has, however, ignored detoxication enzymes, which exhibit catalytic promiscuity. These enzymes dominate drug metabolism and determine drug-drug interactions. The detoxication enzyme glutathione transferase A1-1 (GSTA1-1), exploits a molten globule-like active site to achieve remarkable catalytic promiscuity wherein the substrate-free conformational ensemble is broad with barrierless transitions between states. A quantitative index of catalytic promiscuity is used to compare engineered variants of GSTA1-1 and the catalytic promiscuity correlates strongly with characteristics of the thermodynamic partition function, for the substrate-free enzymes. Access to chemically disparate transition states is encoded by the substrate-free conformational ensemble. Pre-steady state catalytic data confirm an extension of the conformational selection model, wherein different substrates select different starting conformations. The kinetic liability of the conformational breadth is minimized by a smooth landscape. We propose that "local" molten globule behavior optimizes detoxication enzymes. PMID:23649628

Honaker, Matthew T; Acchione, Mauro; Zhang, Wei; Mannervik, Bengt; Atkins, William M

2013-05-06

301

Double resonance spectroscopy of different conformers of the neurotransmitter amphetamine and its clusters with water  

NASA Astrophysics Data System (ADS)

In this paper the conformational landscape of amphetamine in the neutral ground state is examined by both spectroscopy and theory. Several spectroscopic methods are used: laser-induced fluorescence (LIF), resonance-enhanced two-photon ionization (R2PI), dispersed fluorescence and IR/R2PI hole burning spectroscopy. The latter two methods provide for the first time vibrationally resolved spectra of the neutral ground state of dl-amphetamine and the amphetamine (H2O)1,2 complexes. Nine stable conformers of the monomer were found by DFT (B3LYP/6-311++G(d,p)) and ab initio (MP2/6-311++G(d,p)) calculations. For conformer analysis the vibrations observed in the IR/R2PI hole burning and dispersed fluorescence spectra obtained from single vibronic levels (SVLF) of a selected conformer were compared with the results of an ab initio normal mode analysis. By this procedure three S0 ? S1 transitions in the R2PI spectrum were assigned to three different conformer structures. Another weak transition earlier attributed to another conformer could be assigned to a vibronic band of one of the three conformers. Furthermore spectra of amphetamine (H2O)1,2 are tentatively assigned.

Brause, R.; Fricke, H.; Gerhards, M.; Weinkauf, R.; Kleinermanns, K.

2006-08-01

302

Stochastic ensembles, conformationally adaptive teamwork, and enzymatic detoxification.  

PubMed

It has been appreciated for a long time that enzymes exist as conformational ensembles throughout multiple stages of the reactions they catalyze, but there is renewed interest in the functional implications. The energy landscape that results from conformationlly diverse poteins is a complex surface with an energetic topography in multiple dimensions, even at the transition state(s) leading to product formation, and this represents a new paradigm. At the same time there has been renewed interest in conformational ensembles, a new paradigm concerning enzyme function has emerged, wherein catalytic promiscuity has clear biological advantages in some cases. "Useful", or biologically functional, promiscuity or the related behavior of "multifunctionality" can be found in the immune system, enzymatic detoxification, signal transduction, and the evolution of new function from an existing pool of folded protein scaffolds. Experimental evidence supports the widely held assumption that conformational heterogeneity promotes functional promiscuity. The common link between these coevolving paradigms is the inherent structural plasticity and conformational dynamics of proteins that, on one hand, lead to complex but evolutionarily selected energy landscapes and, on the other hand, promote functional promiscuity. Here we consider a logical extension of the overlap between these two nascent paradigms: functionally promiscuous and multifunctional enzymes such as detoxification enzymes are expected to have an ensemble landscape with more states accessible on multiple time scales than substrate specific enzymes. Two attributes of detoxification enzymes become important in the context of conformational ensembles: these enzymes metabolize multiple substrates, often in substrate mixtures, and they can form multiple products from a single substrate. These properties, combined with complex conformational landscapes, lead to the possibility of interesting time-dependent, or emergent, properties. Here we demonstrate these properties with kinetic simulations of nonequilibrium steady state (NESS) behavior resulting from energy landscapes expected for detoxification enzymes. Analogous scenarios with other promiscuous enzymes may be worthy of consideration. PMID:21473615

Atkins, William M; Qian, Hong

2011-04-20

303

Bondi metric and conformal motions  

SciTech Connect

It is shown that there exist no physically significant solutions of the Einstein vacuum field equations, except the trivial one (i.e., Minkowski), for axially and reflection symmetric space-times (Bondi metric) admitting a one-parameter group of conformal motions globally defined on S/sup 2/.

Di Prisco, A.; Herrera, L.; Jimenez, J.; Galina, V.; Ibanez, J.

1987-11-01

304

Cosmology in Conformally Flat Spacetime  

Microsoft Academic Search

A possible solution to cosmological age and redshift-distance difficulties has recently been proposed by applying the appropriate conformally flat spacetime (CFS) coordinates to the standard solution of the field equations in a standard dust model closed universe. Here it is shown that CFS time correctly measures the true age of the universe, thus answering a major theoretical objection to the

Geoffrey Endean

1997-01-01

305

Quantum theory of molecular conformation  

Microsoft Academic Search

Although the given equilibrium conformation of a molecule may be optimized as a function of steric energy, there is no procedure to generate its three-dimensional shape from a spherically symmetrical molecular Hamiltonian. Orbital angular momentum, or the complex phase of the wave function is shown to be of decisive importance in structure generation. While orbital angular momentum cannot be described

Jan C. A. Boeyens

2005-01-01

306

Free fructose is conformationally locked.  

PubMed

Fructose has been examined under isolation conditions using a combination of UV ultrafast laser vaporization and Fourier-transform microwave (FT-MW) spectroscopy. The rotational spectra for the parent, all (six) monosubstituted (13)C species, and two single D species reveal unambiguously that the free hexoketose is conformationally locked in a single dominant ?-pyranose structure. This six-membered-chair skeleton adopts a (2)C(5) configuration (equivalent to (1)C(4) in aldoses). The free-molecule structure sharply contrasts with the furanose form observed in biochemically relevant polysaccharides, like sucrose. The structure of free fructose has been determined experimentally using substitution and effective structures. The enhanced stability of the observed conformation is primarily attributed to a cooperative network of five intramolecular O-H···O hydrogen bonds and stabilization of both endo and exo anomeric effects. Breaking a single intramolecular hydrogen bond destabilizes the free molecule by more than 10 kJ mol(-1). The structural results are compared to ribose, recently examined with rotational resolution, where six different conformations coexist with similar conformational energies. In addition, several DFT and ab initio methods and basis sets are benchmarked with the experimental data. PMID:23346993

Cocinero, Emilio J; Lesarri, Alberto; Écija, Patricia; Cimas, Álvaro; Davis, Benjamin G; Basterretxea, Francisco J; Fernández, José A; Castaño, Fernando

2013-02-07

307

Precision conformal optics technology program  

NASA Astrophysics Data System (ADS)

Conformal optics are defined as optics that deviate from conventional form to best satisfy the contour and shape needs of system platforms. Precision Conformal Optics Technology (PCOT), a comprehensive 48 month program funded by the Defense Advanced Research Program Agency (DARPA) and the U. S. Army Missile Research, Development, and Engineering Center (MRDEC), assessed the potential benefits achieved by use of conformal optics on a variety of U.S. weapon systems. Also addressed were all barriers impeding conformal optics use. The PCOT program was executed by a consortium of organizations ranging from major U.S. defense prime contractors, to small businesses, and academia. The diversity of organizations encouraged synergy across a broad array of skills and perspectives. Smooth team interaction was made possible by the 845 contractual structure of the program. Benefits identified by the PCOT consortium included major reductions in aerodynamic drag (by as much as 50%), reduced time-to-targets (by as much as 60%), and reduced weapon signatures. Impediments addressed included inadequacies in optical design tools, optical manufacturing methods and equipment, optical testing, and system integration. The PCOT program was successfully completed with a demonstration of a highly contoured missile dome, which reduced overall missile drag by 25%, and led to a predicted twofold increase in missile range.

Trotta, Patrick A.

2001-09-01

308

High conformance oil recovery process  

Microsoft Academic Search

The conformance of an enhanced oil recovery process, including waterflood, surfactant or other chemicalized water flood process, in a formation containing at least two strata or zones of varying permeability, the permeability of one zone being at least 50 percent greater than the permeability of the other zone, is improved by flooding until the higher permeability zone has been depleted,

J. E. Varnon; M. V. Kudchadker; A. Brown; L. E. Whittington

1979-01-01

309

Conformal properties of pseudoparticle configurations  

Microsoft Academic Search

The known Euclidean Yang-Mills pseudoparticle solutions with Pontryagin index n are parametrized by 5 n constants describing the size and location of each pseudoparticle. By insisting on conformal covariance of the solutions, we show that more general solutions exist-they are parametrized by 5 n + 4 constants. We further demonstrate that the additional degrees of freedom are not gauge artifacts

R. Jackiw; C. Nohl; C. Rebbi

1977-01-01

310

Temperature: Human Regulating, Ants Conforming  

ERIC Educational Resources Information Center

|Biological processes speed up as temperature rises. Procedures for demonstrating this with ants traveling on trails, and data gathered by students on the Argentine ant ("Linepithema humile") are presented. The concepts of temperature regulation and conformity are detailed with a focus on the processes rather than on terms that label the…

Clopton, Joe R.

2007-01-01

311

Higher Moments in Conformal Turbulence  

NASA Astrophysics Data System (ADS)

Physical consequences of conformal turbulence are obtained by calculating higher moments in the inertial range with constant enstrophy flux cascade. We have also studied the boundary effects in these higher moments. Our results show deviations from Kolmogorov-type scaling laws.

Chen, Chia-Chu

312

Critical percolation and conformal invariance  

NASA Astrophysics Data System (ADS)

Many 2D critical lattice models are believed to have conformally invariant scaling limits. This belief allowed physicists to predict (unrigorously) many of their properties, including exact values of various dimensions and scaling exponents. We describe some of the recent progress in the mathematical understanding of these models, using critical percolation as an example.

Smirnov, Stanislav

2006-03-01

313

Critical percolation and conformal invariance  

Microsoft Academic Search

Many 2D critical lattice models are believed to have conformally invariant scaling limits. This belief allowed physicists to predict (unrigorously) many of their properties, including exact values of various dimensions and scaling exponents. We describe some of the recent progress in the mathematical understanding of these models, using critical percolation as an example.

Stanislav Smirnov

2006-01-01

314

Coordinate confusion in conformal cosmology  

Microsoft Academic Search

A straightforward interpretation of standard Friedmann-Lemaître-Robertson-Walker (FLRW) cosmologies is that objects move apart because of the expansion of space, and that sufficiently distant galaxies must be receding at velocities exceeding the speed of light. Recently, however, it has been suggested that a simple transformation into conformal coordinates can remove superluminal recession velocities, and hence the concept of the expansion of

Geraint F. Lewis; Matthew J. Francis; Luke A. Barnes; J. Berian James

2007-01-01

315

Phase transitions in M-theory and F-theory  

Microsoft Academic Search

Phase transitions are studied in M-theory and F-theory. In M-theory compactification to five dimensions on a Calabi-Yau, one can find topology-changing transitions similar to those seen in conformal field theory, but the non-geometrical phases known in conformal field theory are absent. At boundaries of moduli space where such phases might have been expected, the moduli space ends, by a conventional

Edward Witten

1996-01-01

316

On the Roles of Substrate Binding and Hinge Unfolding in Conformational Changes of Adenylate Kinase  

SciTech Connect

We characterized the conformational change of adenylate kinase (AK) between open and closed forms by conducting five all-atom molecular-dynamics simulations, each of 100 ns duration. Different initial structures and substrate binding configurations were used to probe the pathways of AK conformational change in explicit solvent, and no bias potential was applied. A complete closed-to-open and a partial open-to-closed transition were observed, demonstrating the direct impact of substrate-mediated interactions on shifting protein conformation. The sampled configurations suggest two possible pathways for connecting the open and closed structures of AK, affirming the prediction made based on available x-ray structures and earlier works of coarse-grained modeling. The trajectories of the all-atom molecular-dynamics simulations revealed the complexity of protein dynamics and the coupling between different domains during conformational change. Calculations of solvent density and density fluctuations surrounding AK did not show prominent variation during the transition between closed and open forms. Finally, we characterized the effects of local unfolding of an important hinge near Pro177 on the closed-to-open transition of AK and identified a novel mechanism by which hinge unfolding modulates protein conformational change. The local unfolding of Pro177 hinge induces alternative tertiary contacts that stabilize the closed structure and prevent the opening transition.

Brokaw, Jason B.; Chu, Jhih-wei

2010-11-17

317

Modeling the Conformational Changes Underlying Channel Opening in CFTR  

PubMed Central

Mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator protein (CFTR) cause cystic fibrosis (CF), the most common life-shortening genetic disease among Caucasians. Although general features of the structure of CFTR have been predicted from homology models, the conformational changes that result in channel opening and closing have yet to be resolved. We created new closed- and open-state homology models of CFTR, and performed targeted molecular dynamics simulations of the conformational transitions in a channel opening event. The simulations predict a conformational wave that starts at the nucleotide binding domains and ends with the formation of an open conduction pathway. Changes in side-chain interactions are observed in all major domains of the protein, and experimental confirmation was obtained for a novel intra-protein salt bridge that breaks near the end of the transition. The models and simulation add to our understanding of the mechanism of ATP-dependent gating in this disease-relevant ion channel.

Rahman, Kazi S.; Cui, Guiying; Harvey, Stephen C.; McCarty, Nael A.

2013-01-01

318

Modeling the Conformational Changes Underlying Channel Opening in CFTR.  

PubMed

Mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator protein (CFTR) cause cystic fibrosis (CF), the most common life-shortening genetic disease among Caucasians. Although general features of the structure of CFTR have been predicted from homology models, the conformational changes that result in channel opening and closing have yet to be resolved. We created new closed- and open-state homology models of CFTR, and performed targeted molecular dynamics simulations of the conformational transitions in a channel opening event. The simulations predict a conformational wave that starts at the nucleotide binding domains and ends with the formation of an open conduction pathway. Changes in side-chain interactions are observed in all major domains of the protein, and experimental confirmation was obtained for a novel intra-protein salt bridge that breaks near the end of the transition. The models and simulation add to our understanding of the mechanism of ATP-dependent gating in this disease-relevant ion channel. PMID:24086355

Rahman, Kazi S; Cui, Guiying; Harvey, Stephen C; McCarty, Nael A

2013-09-27

319

Electrochemical evidence on the molten globule conformation of cytochrome c.  

PubMed

To explore a new approach for characterizing the molten globule conformation, cyclic voltammetric studies of salt induced transitions at acidic pH of cyt c have been carried out. The use of modified electrodes has made the observation of direct electrochemistry in native cyt c possible. However, most of these electrodes do not show reversible responses at acidic pH, due to the fact that, for this system, a deprotonated electrode surface is needed. In these studies, we have used a 6-mercaptopurine and cysteine-modified gold electrodes which are effective for direct rapid electron transfer to cyt c, even in acid solutions. The change in the absorption bands of cyt c are used to monitor the conformational states and, hence, to compare the voltammetric results. Under the experimental conditions where the A state of cyt c is obtained, a reversible voltammetric signal is observed. The midpoint peak potentials are found to be very close to the formal potential of native cyt c. Results are discussed in terms of a cooperative two-state transition between the acid unfolded and the globular acidic states of cyt c. This finding establishes, for the first time, the similarity of both the native and the molten globule-like conformations in terms of its redox properties. PMID:9434113

Pineda, T; Sevilla, J M; Román, A J; Blázquez, M

1997-12-01

320

Nucleosome conformation: pH and organic solvent effects.  

PubMed

Monomer nucleosomes (nu 1) from chicken erythrocyte nuclei were examined in aqueous buffers (8 greater than pH greater than 3) and in solvent mixtures (i.e., water and ethanol, ethylene glycol, dioxane, dimethyl sulfoxide, 2-methyl-2,4-pentanediol, polyethylene glycol, sucrose, or urea). Circular dichroism, laser Raman spectroscopy of nu 1, and the fluorescence of nu 1 labeled with N-(3-pyrene) maleimide on thiol groups of H3 histone were employed to detect conformational transitions in nu 1. The results of pH studies were as follows: 5.5 greater than pH greater than 4.8, suppression of DNA ellipticity and no change of histone alpha-helix; 4.6 greater than pH greater than 4.2 an irreversible increase in the B character of DNA, a slight loss of histone alpha-helix, and a parallel loss of pyrene excimer fluorescence; 4 greater than pH, aggregation of nu 1 and protonation of the DNA bases C and A. Results obtained in the studies of nu 1 in solvent mixtures included the following: sharp conformational transitions that variously involved an increase in the B character of DNA, a slight loss of histone alpha-helix, and a loss of pyrene excimer. Different solvents required different concentrations to effect these conformational changes. PMID:31605

Zama, M; Olins, D E; Prescott, B; Thomas, G J

1978-10-01

321

Single-Molecule Protein Conformational Dynamics in Enzymatic Reactions  

NASA Astrophysics Data System (ADS)

Enzymes involve many critical biological processes, and for some extends, the biological clock of a living cell is often regulated by enzymatic reactions. An enzymatic reaction involves active substrate-enzyme complex formation, chemical transformation, and product releasing, as we know of the Mechalis-Menten mechanism. Enzymes can change the biological reaction pathways and accelerate the reaction rate by thousands and even millions of times. It is the enzyme-substrate interaction and complex formation that play a critical role in defining the enzymatic reaction landscape, including reaction potential surface, transition states of chemical transformation, and oscillatory reaction pathways. Subtle conformational changes play a crucial role in enzyme functions, and these protein conformations are highly dynamic rather than being static. Using only a static structural characterization, from an ensemble-averaged measurement at equilibrium is often inadequate in predicting dynamic conformations and understanding correlated enzyme functions in real time involving in nonequilibrium, multiple-step, multiple-conformation complex chemical interactions and transformations.

Lu, H. Peter

322

Work transitions.  

PubMed

Individuals make choices in, and adjust to, a world of work that is often a moving target. Because work is so central to human functioning, and transitions in and out of work can have major mental health repercussions, the authors argue that applied psychologists in health services need to understand those transitions. This article focuses on the different types of transition throughout a person's working life and the resources needed at different stages to ensure the success of these transitions. The authors start by examining the roles of capability and adaptability in supporting and facilitating adjustment to work transitions and their relation to identity development. They then examine the role of social and institutional contexts in shaping work transitions and their outcomes. The authors focus on voluntary versus involuntary transitions and then broaden the lens in discussing the policy implications of research on work transitions. PMID:18473609

Fouad, Nadya A; Bynner, John

323

Probing Conformational Changes of Gramicidin Ion Channels by Single-Molecule Patch-Clamp Fluorescence Microscopy  

PubMed Central

Complex conformational changes influence and regulate the dynamics of ion channels. Such conformational changes are stochastic and often inhomogeneous, which makes it extremely difficult, if not impossible, to characterize them by ensemble-averaged experiments or by single-channel recordings of the electric current that report the open-closed events but do not specifically probe the associated conformational changes. Here, we report our studies on ion channel conformational changes using a new approach, patch-clamp fluorescence microscopy, which simultaneously combines single-molecule fluorescence spectroscopy and single-channel current recordings to probe the open-closed transitions and the conformational dynamics of individual ion channels. We demonstrate patch-clamp fluorescence microscopy by measuring gramicidin ion channel conformational changes in a lipid bilayer formed at a patch-clamp micropipette tip under a buffer solution. By measuring single-pair fluorescence resonance energy transfer and fluorescence self-quenching from dye-labeled gramicidin channels, we observed that the efficiency of single-pair fluorescence resonance energy transfer and self-quenching is widely distributed, which reflects a broad distribution of conformations. Our results strongly suggest a hitherto undetectable correlation between the multiple conformational states of the gramicidin channel and its closed and open states in a lipid bilayer.

Harms, Greg S.; Orr, Galya; Montal, Mauricio; Thrall, Brian D.; Colson, Steve D.; Lu, H. Peter

2003-01-01

324

40 CFR 52.2133 - General conformity.  

Code of Federal Regulations, 2013 CFR

...OF IMPLEMENTATION PLANS (CONTINUED) South Carolina § 52.2133 General conformity...Conformity regulations adopted into the South Carolina State Implementation Plan which were submitted on November 8, 1996. South Carolina incorporated by reference...

2013-07-01

325

China's urban transition.  

PubMed

This article describes recent changes in urban patterns in Shanghai-Nanjing, Beijing-Tianjin-Tangshan, Canton-Hong Kong, and Dalian-Shenyang. The urban patterns in these metropolitan areas are viewed as part of an urban transition that is responding to population growth, a structural shift in employment, relaxed rules on migration and household registration, and foreign investment and trade. It is argued that these metropolitan coastal areas will form the key growth centers and will lead China's economic development. Urban transition is defined as the shift from rural to urban and from agricultural employment to industrial, commercial, or service employment. China's large cities always dominated as important centers of politics and trade. The recent shift is from interior to coastal cities due to a new world view and a movement away from the isolationism of prior centuries. It is assumed that cities are formed to take advantage of economies of scale in production, consumption, and distribution and to conform to regional specialization. Governments can intervene in growth processes. China's development of cities reflects state controls and market forces. The size and scale of China's population influenced the development process, which resulted in differences in the shape and process of the urban transition. It was under Chinese communism that cities became more than a set of discrete regional urban systems. Reference is made to Oshima's model of change that is specific to monsoon countries. Oshima argues that monsoon agricultural conditions require a distinct strategy based on full employment in order to achieve industrial transition. Rice cultivation requires a large and disciplined labor force. The discussion focuses on other models as well, such as the McGee's model of the extended metropolis and its extension by Zhou Yixing to China. China's changes may not follow Skeldon's models of urbanization in developing countries, because of state control of migration. However, the longer migrants remain in cities the more likely Skeldon's models of early European transitions apply to China's urban transition. PMID:12178548

Pannell, C

326

Protein conformational space in higher order ?-? maps  

PubMed Central

We have mapped protein conformational space from two to seven residue lengths by employing multidimensional scaling on a data matrix composed of pair-wise angular distances for multiple ?-? values collected from high-resolution protein structures. The resulting global maps show clustering of peptide conformations that reveals a dramatic reduction of conformational space as sampled by experimentally observed peptides. Each map can be viewed as a higher order ?-? plot defining regions of space that are conformationally allowed.

Sims, Gregory E.; Choi, In-Geol; Kim, Sung-Hou

2005-01-01

327

Stabilizing the boat conformation of cyclohexane rings  

SciTech Connect

In calculating the energetics for various conformers of the A, B, and C series of hopanoid hydrocarbons present in mature oil reservoirs, we find that the B series prefers the boat conformation (by 1.3-2.5 kcal/mol) for the D cyclohexane ring. We analyze the structural elements responsible for stabilizing this boat conformation, identify the key features, and illustrate how one might stabilize boat conformations of other systems. 5 refs., 3 figs., 2 tabs.

Dasgupta, S.; Goddard, W.A. III [California Inst. of Technology, Pasadena, CA (United States); Moldowan, J.M. [Stanford Univ., CA (United States); Carlson, R.M.K. [Chevron Petroleum Technology Company, Richmond, CA (United States); Goddard, W.A. III. [California Inst. of Technology, Pasadena, CA (United States)

1995-06-21

328

Guiding light with conformal transformations.  

PubMed

The past decade has seen a revolution in electromagnetics due to the development of metamaterials. These artificial composites have been fashioned to exhibit exotic effects such as a negative index of refraction. However, the full potential of metamaterial devices has only been hinted at. By combining metamaterials with transformation optics (TO), researchers have demonstrated an invisibility cloak. Subsequently, quasi-conformal mapping was used to create a device that exhibited a broadband cloaking effect. Here we extend this latter approach to a strictly conformal mapping to create reflection less, inherently isotropic, and broadband photonic devices. Our method combines the novel effects of TO with the practicality of all-dielectric construction. We show that our structures are capable of guiding light in an almost arbitrary fashion over an unprecedented range of frequencies. PMID:19687966

Landy, Nathan I; Padilla, Willie J

2009-08-17

329

New criterion for conformational polymorphism  

SciTech Connect

An analysis of nonvalent interactions in 29 crystal structures of compounds that have the C{sub a}H{sub b}N{sub c}O{sub d} composition (salicylaldoxime, glycine, and 2,4,6,8,10,12-hexaazaisowurzitane) and form polymorphic modifications is performed using molecular Voronoi-Dirichlet polyhedra. It is found that each conformational polymorph is characterized by a unique combination of the types of intramolecular and intermolecular nonvalent interactions. It is shown that a criterion which takes into account the total number of intramolecular nonvalent contacts and their distribution depending on the nature of neighboring atoms and the rank of faces of molecular Voronoi-Dirichlet polyhedra can be used to reveal conformational polymorphs.

Serezhkin, V. N., E-mail: serezhkin@ssu.samara.ru; Serezhkina, L. B. [Samara State University (Russian Federation)

2012-01-15

330

Transitions between secondary structures in isolated polyalanines  

NASA Astrophysics Data System (ADS)

Monte Carlo simulations of gas-phase polyalanine peptides have been carried out with the Amber ff96 force field. A low-temperature structural transition takes place between the ?-helix stable conformation and ?-sheet structures, followed by the unfolding phase change. The transition state ensembles connecting the helix and sheet conformations are investigated by sampling the energy landscape along specific geometric order parameters as putative reaction coordinates, namely the electric dipole ?, the end-to-end distance d, and the gyration radius Rg. By performing series of shooting trajectories, the committor probabilities and their distributions are obtained, revealing that only the electric dipole provides a satisfactory transition coordinate for the ??? interconversion. The nucleus at the transition is found to have a high helical content.

Calvo, F.; Poulain, P.

2009-01-01

331

Alternative conformations in Escherichia coli 16S ribosomal RNA.  

PubMed Central

Partially denatured 16S rRNA from 30S ribosomes shows features of secondary structure in electron microscopy that correspond to the well accepted secondary structure model derived from chemical modification and phylogenetic data. However, a very different conformation is seen in precursor 16S rRNA sequences contained within 30S pre-rRNA transcripts: the major 5'-terminal loop is absent, and several additional quite stable large loops, symmetrically placed in the molecule, are present. Features of the alternative structure are also seen in mature 16S rRNA from Escherichia coli and from two Bacillus species when heated in certain buffers. Microscopy thus reveals specific features of alternative conformations and their relative stabilities, suggesting a possible transition during ribosome formation. Images

Klein, B K; Staden, A; Schlessinger, D

1985-01-01

332

Permeable conformal walls and holography  

Microsoft Academic Search

We study conformal field theories in two dimensions separated by domain walls, which preserve at least one Virasoro algebra. We develop tools to study such domain walls, extending and clarifying the concept of `folding' discussed in the condensed-matter literature. We analyze the conditions for unbroken supersymmetry, and discuss the holographic duals in AdS3 when they exist. One of the interesting

Constantin Bachas; Jan de Boer; Robbert Dijkgraaf; Hirosi Ooguri

2002-01-01

333

An introduction to conformal Ricci flow  

Microsoft Academic Search

We introduce a variation of the classical Ricci flow equation that modifies the unit volume constraint of that equation to a scalar curvature constraint. The resulting equations are named the conformal Ricci flow equations because of the role that conformal geometry plays in constraining the scalar curvature and because these equations are the vector field sum of a conformal flow

Arthur E. Fischer

2004-01-01

334

Conformal Geodesics on Vacuum Space-times  

NASA Astrophysics Data System (ADS)

We discuss properties of conformal geodesics on general, vacuum, and warped product space-times and derive a system of conformal deviation equations. It is then shown how to construct on the Schwarzschild-Kruskal space-time globally defined systems of conformal Gauss coordinates which extend smoothly and without degeneracy to future and past null infinity.

Friedrich, Helmut

335

Contact conformers in crystals of coordination compounds  

Microsoft Academic Search

In a continuation of the systematic study of contact conformers (coexisting molecules having different structures), a comparison of the structures of symmetrically independent molecules inthe crystals of 37 coordination compounds have been compared. Fourteen cases of contact conformers have been detected and systematized. The earlier suggestion that contact conformers are more typical of crystals of coordination compounds than of organic

E. É. Lavut; P. M. Zorkii; N. Yu. Chernikova

1982-01-01

336

Conformal inflation, modulated reheating, and WMAP5  

Microsoft Academic Search

We investigate density perturbations generated through modulated reheating while inflation is driven by a conformally coupled scalar field. A large running of the spectral index is obtained, which reflects the basic nature of conformal inflation that higher-order time derivatives of the Hubble parameter during inflation are not necessarily small. This feature may allow us to distinguish between conformal inflation models

Takeshi Kobayashi; Shinji Mukohyama

2009-01-01

337

Reinforcement Learning Signal Predicts Social Conformity  

Microsoft Academic Search

SUMMARY We often change our decisions and judgments to conform with normative group behavior. However, the neural mechanisms of social conformity remain unclear. Here we show, using functional magnetic resonance imaging, that conformity is based on mechanisms that comply with principles of reinforce- ment learning. We found that individual judgments of facial attractiveness are adjusted in line with group opinion.

Vasily Klucharev; Kaisa Hytönen; Mark Rijpkema; Ale Smidts; Guillén Fernández

2009-01-01

338

Protein conformational diversity modulates sequence divergence.  

PubMed

It is well established that the conservation of protein structure during evolution constrains sequence divergence. The conservation of certain physicochemical environments to preserve protein folds and then the biological function originates a site-specific structurally constrained substitution pattern. However, protein native structure is not unique. It is known that the native state is better described by an ensemble of conformers in a dynamic equilibrium. In this work, we studied the influence of conformational diversity in sequence divergence and protein evolution. For this purpose, we derived a set of 900 proteins with different degrees of conformational diversity from the PCDB database, a conformer database. With the aid of a structurally constrained protein evolutionary model, we explored the influence of the different conformations on sequence divergence. We found that the presence of conformational diversity strongly modulates the substitution pattern. Although the conformers share several of the structurally constrained sites, 30% of them are conformer specific. Also, we found that in 76% of the proteins studied, a single conformer outperforms the others in the prediction of sequence divergence. It is interesting to note that this conformer is usually the one that binds ligands participating in the biological function of the protein. The existence of a conformer-specific site-substitution pattern indicates that conformational diversity could play a central role in modulating protein evolution. Furthermore, our findings suggest that new evolutionary models and bioinformatics tools should be developed taking into account this substitution bias. PMID:22396525

Juritz, Ezequiel; Palopoli, Nicolas; Fornasari, Maria Silvina; Fernandez-Alberti, Sebastian; Parisi, Gustavo

2012-03-06

339

Conformal blocks in the large D limit  

NASA Astrophysics Data System (ADS)

We derive conformal blocks in an inverse spacetime dimension expansion. In this large D limit, the blocks are naturally written in terms of a new combination of conformal cross-ratios. We comment on the implications for the conformal bootstrap at large D.

Fitzpatrick, A. Liam; Kaplan, Jared; Poland, David

2013-08-01

340

Phase transition in the Sznajd model with independence  

NASA Astrophysics Data System (ADS)

We propose a model of opinion dynamics which describes two major types of social influence —conformity and independence. Conformity in our model is described by the so-called outflow dynamics (known as Sznajd model). According to sociologists' suggestions, we introduce also a second type of social influence, known in social psychology as independence. Various social experiments have shown that the level of conformity depends on the society. We introduce this level as a parameter of the model and show that there is a continuous phase transition between conformity and independence.

Sznajd-Weron, K.; Tabiszewski, M.; Timpanaro, A. M.

2011-11-01

341

New potentials for conformal mechanics  

NASA Astrophysics Data System (ADS)

We find under some mild assumptions that the most general potential of one-dimensional conformal systems with time-independent couplings is expressed as V = V0 + V1, where V0 is a homogeneous function with respect to a homothetic motion in configuration space and V1 is determined from an equation with source a homothetic potential. Such systems admit at most an SL(2,{R}) conformal symmetry which, depending on the couplings, is embedded in {Diff}({R}) in three different ways. In one case, SL(2,{R}) is also embedded in Diff(S1). Examples of such models include those with potential V = ?x2 + ?x-2 for arbitrary couplings ? and ?, the Calogero models with harmonic oscillator couplings and nonlinear models with suitable metrics and potentials. In addition, we give the conditions on the couplings for a class of gauge theories to admit a SL(2,{R}) conformal symmetry. We present examples of such systems with general gauge groups and global symmetries that include the isometries of AdS2 × S3 and AdS2 × S3 × S3 which arise as backgrounds in AdS2/CFT1.

Papadopoulos, G.

2013-04-01

342

Limit cycles and conformal invariance  

NASA Astrophysics Data System (ADS)

There is a widely held belief that conformal field theories (CFTs) require zero beta functions. Nevertheless, the work of Jack and Osborn implies that the beta functions are not actually the quantites that decide conformality, but until recently no such behavior had been exhibited. Our recent work has led to the discovery of CFTs with nonzero beta functions, more precisely CFTs that live on recurrent trajectories, e.g., limit cycles, of the beta-function vector field. To demonstrate this we study the S function of Jack and Osborn. We use Weyl consistency conditions to show that it vanishes at fixed points and agrees with the generator Q of limit cycles on them. Moreover, we compute S to third order in perturbation theory, and explicitly verify that it agrees with our previous determinations of Q. A byproduct of our analysis is that, in perturbation theory, unitarity and scale invariance imply conformal invariance in four-dimensional quantum field theories. Finally, we study some properties of these new, "cyclic" CFTs, and point out that the a-theorem still governs the asymptotic behavior of renormalization-group flows.

Fortin, Jean-François; Grinstein, Benjamín; Stergiou, Andreas

2013-01-01

343

DFT study of conformational and spectroscopic properties of yatakemycin.  

PubMed

Molecular structure and conformational preferences of yatakemycin, a novel and exceptionally potent antitumor agent, have been investigated using the density functional theory (DFT) formalism. From the relative stability of various possible conformations, it is found that two conformers are nearly isoenergetic and markedly more stable than the others in the gas phase. To test the effect of polar mediums, the relative energies have been recalculated using the self-consistent reaction field method. Thus, the most stable conformer of the isolated molecule in the gas phase is expected to be still more preferred in solution. The molecular structure of yatakemycin has also been studied by means of its spectroscopic properties. The DFT results satisfactorily reproduce the experimental data and corroborate the reliability of the structural characterization advanced for yatakemycin. The lowest-energy electronic transitions have been interpreted with time-dependent DFT calculations. Notably, the strong IR band observed at 2852 cm(-1) is unambiguously assigned to the O-H stretching of the (C7)O-H...O(C12) fragment, linked by a strong intramolecular H-bond, and may be viewed as a distinctive fingerprint of yatakemycin. Furthermore, the calculated set of NMR chemical shifts of carbonyl carbon atoms and indole protons, the most sensitive to stereoelectronic factors, is consistent with experiment. The effects of both protonation and oxidation on the geometry of the most stable conformer have also been studied. With reference to yatakemycin's DNA alkylation properties, the structure of the yatakemycin-adenine adduct has been theoretically modeled and found to be consistent with experimental spectroscopic evidence. PMID:17564422

Pichierri, Fabio; Galasso, Vinicio

2007-06-12

344

Conformational control of benzyl-o-carboranylbenzene derivatives and molecular encapsulation of acetone in the dynamically formed space of 1,3,5-tris(2-benzyl-o-carboran-1-yl)benzene.  

PubMed

A 1,3,5-substituted benzene platform has been widely used in the fields of supramolecular chemistry and molecular recognition. Here, we show that 1,3,5-tris(2-benzyl-o-carboran-1-yl)benzene 6 exhibits solvent-dependent conformation in the crystalline state. Recrystallization from dichloromethane-n-pentane gave the anti conformation 6-anti, while recrystallization from methanol-acetone gave the syn conformation 6-syn, in which the three benzyl-o-carboranyl moieties are located to one side of the central benzene ring. Interestingly, one acetone molecule is captured in the ?-rich space of 6-syn and two complexes facing each other encapsulate two acetone molecules in a ?-rich container formed by the eight benzene rings. The inclusion involves several weak interactions, that is, T-shaped C-H···? interactions, and C-H···O and C-H···? interactions. Two C-H···O interactions involving benzylic C-H hydrogens activated by the electron-withdrawing character of the o-carborane cage and the oxygen atom of the acetone seem to be the most important. DFT calculations indicate that the binding energy for entrapment of acetone is 6.6 kcal/mol. Inclusion of acetone is achieved through not only multiple C-H···O interactions but also a number of C-H···? interactions. The third benzyl-o-carborane moiety is fixed in the syn conformation by intramolecular and intermolecular C-H···? interactions. PMID:21058729

Songkram, Chalermkiat; Ohta, Kiminori; Yamaguchi, Kentaro; Pichierri, Fabio; Endo, Yasuyuki

2010-11-08

345

Conformational mobility of small molecules in glass-forming solutions studied by FTIR spectroscopy.  

PubMed

Small molecules with two or more stable conformations when embedded in a glass-forming liquid (matrix) serve the role of "conformational probes", i.e., their conformational transitions are used to follow local mobility in the matrix. In the present study, conformational probes were embedded in low-molecular-weight glass-forming liquids, and the molecular mobility was studied in a broad temperature range including the glass transition temperature (T(g)). Paraffin oil, dibutylphthalate, bis(2-ethylhexyl)phthalate and isopropylbenzene were used as glass-forming liquids while 1,2-dichloroethane, 1,2-diphenylethane, chlorocyclohexane and bromocyclohexane were used as conformational probes. For some of the matrix/probe systems, the conformational mobility was found to freeze-in at T(g), while for the others it froze-in at certain temperatures T(f)

Fishman, A I; Noskov, A I; Stolov, A A

2012-02-09

346

Simple Model Study of Phase Transition Properties of Isolated and Aggregated Protein  

NASA Astrophysics Data System (ADS)

We investigate the phase transition properties of isolated and aggregated protein by exhaustive numerical study in the confined conformation space with maximally compact lattice model. The study within the confined conformation space shows some general folding properties. Various sequences show different folding properties: two-state folding, three-state folding and prion-like folding behavior. We find that the aggregated protein holds a more evident transition than isolated one and the transition temperature is generally lower than that in isolated case.

Ji, Yong-Yun; Yi, Wei-Qi; Zhang, Lin-Xi

2011-03-01

347

Visualization of the maturation transition in bacteriophage P22 by electron cryomicroscopy1  

Microsoft Academic Search

Large-scale conformational transitions are involved in the life-cycle of many types of virus. The dsDNA phages, herpesviruses, and adeno- viruses must undergo a maturation transition in the course of DNA packaging to convert a scaffolding-containing precursor capsid to the DNA-containing mature virion. This conformational transition converts the procapsid, which is smaller, rounder, and displays a distinctive skew- ing of the

Zhixian Zhang; Barrie Greene; Pamela A. Thuman-Commike; Joanita Jakana; Peter E. Prevelige Jr; Jonathan King; Wah Chiu

2000-01-01

348

Molecular basis for solvent dependent morphologies observed on electrosprayed surfaces.  

PubMed

We study the causes of the observed tunable hydrophobicity of poly(styrene-co-perfluoroalkyl ethylacrylate) electrosprayed in THF, DMF, and THF?:?DMF (1?:?1) solvents. Under the assumption that equilibrium morphologies in the solvent significantly affect the patterns observed on electrosprayed surfaces, we use atomistic and coarse-grained simulations supported by dynamic light scattering (DLS) experiments to focus on the parameters that affect the resulting morphology of superhydrophobic electrosprayed beads. The differing equilibrium chain size distributions in these solvents examined by DLS are corroborated by chain dimensions obtained via molecular dynamics simulations. Mesoscopic morphologies monitored by dissipative particle dynamics simulations explain experimental observations; in particular, the preference of the polymer for THF over DMF in the binary mixture rationalizes the dual scale roughness driven by stable microphase separation. Drying phenomena that affect resultant dual-scale roughness are described in three stages, each interpreted by concentration dependent diffusion and surface mass transfer coefficients of the solvents. Irrespective of the presence of polar groups in the structure, a conflict between the lower-boiling point solvent adhering to the polymer and the less volatile solvent abundant in the bulk leads to perfectly hydrophobic surfaces. PMID:24056882

Ozden-Yenigun, Elif; Simsek, Eren; Menceloglu, Yusuf Ziya; Atilgan, Canan

2013-10-01

349

Parity Doubling and the S Parameter below the Conformal Window  

NASA Astrophysics Data System (ADS)

We describe a lattice simulation of the masses and decay constants of the lowest-lying vector and axial resonances, and the electroweak S parameter, in an SU(3) gauge theory with Nf=2 and 6 fermions in the fundamental representation. The spectrum becomes more parity doubled and the S parameter per electroweak doublet decreases when Nf is increased from 2 to 6, motivating study of these trends as Nf is increased further, toward the critical value for transition from confinement to infrared conformality.

Appelquist, T.; Babich, R.; Brower, R. C.; Cheng, M.; Clark, M. A.; Cohen, S. D.; Fleming, G. T.; Kiskis, J.; Lin, M. F.; Neil, E. T.; Osborn, J. C.; Rebbi, C.; Schaich, D.; Vranas, P. M.

2011-06-01

350

Parity Doubling and the S Parameter Below the Conformal Window  

SciTech Connect

We describe a lattice simulation of the masses and decay constants of the lowest-lying vector and axial resonances, and the electroweak S parameter, in an SU(3) gauge theory with N{sub f} = 2 and 6 fermions in the fundamental representation. The spectrum becomes more parity doubled and the S parameter per electroweak doublet decreases when N{sub f} is increased from 2 to 6, motivating study of these trends as N{sub f} is increased further, toward the critical value for transition from confinement to infrared conformality.

Appelquist, T; Babich, R; Brower, R C; Cheng, M; Clark, M A; Cohen, S D; Fleming, G T; Kiskis, J; Lin, M F; Neil, E T; Osborn, J C; Rebbi, C; Schaich, D; Vranas, P M

2011-10-21

351

Calculation of conformations and vibrational spectra of a monomeric fragment of the 2,6-carboxymethyl cellulose molecule  

NASA Astrophysics Data System (ADS)

A theoretical conformational analysis has been carried out for the side substituents of a fragment of the molecule for 2,6-carboxymethyl cellulose (a water-soluble cellulose ether), and the frequencies and the potential energy distribution of the normal vibrations have been calculated for the most stable conformers of the ether groups of this fragment in the approximation of the molecular mechanics method. It has been shown that the most stable conformers are those that have the conformations gg, t, g-, g-, g--for the groups of atoms on the bonds C5-C6, C6-O6, C13-O6, C10-C13, C10-O9 and the conformations g+g-, g+, g-, g-; g+g-, g-, g-, g-; g+g-, g-, g+, t for the groups of atoms on the bonds C2-O2, C11-O2, C7-C11, C7-O8. Comparative analysis of the calculated frequencies and the potential energy distribution of the normal vibrations for 13 of the most stable conformers showed, as in the case of the 2,6-hydroxyethyl cellulose molecule, that the frequencies and modes of the normal vibrations are highly sensitive to conformational transitions in the analyzed spectral region (800-1500 cm-1). The characteristic patterns for the change in the frequencies and modes of the normal vibrations have been established in connection with conformational transitions within both side substituents. The observed conformational lability of the bulky substituents in the cellulose ether molecules and its manifestations in the vibrational spectrum provide a basis for hypothesizing that one of the major mechanisms for the process of their thermal gelation in aqueous solutions is conformational transitions within these substituents.

Andrianov, V. M.

2007-01-01

352

The Force-Driven Conformations of Heparin Studied with Single Molecule Force Microscopy  

PubMed Central

Using single molecule force spectroscopy we examine the response of heparin chains to mechanical stretching. We find that at forces below 200 pN heparin behaves as a simple entropic spring. At ?200 pN heparin displays a large enthalpic elasticity, which is evident as a pronounced plateau in the force-extension relationship. We determine that this enthalpic elasticity is produced by sugar rings of heparin flipping to more energetic and more extended conformations. We estimate that in vivo, the forces which stretch heparin are comparable to the forces that trigger conformational transitions in our single molecule atomic force microscopy measurements. We hypothesize that these conformational transitions have biological significance in that they provide a mechanism to finely regulate the affinity of various ligands toward heparin, for example, in secretory granules undergoing exocytosis and during the mechanical interactions between cells and the extracellular matrix.

Marszalek, Piotr E.; Oberhauser, Andres F.; Li, Hongbin; Fernandez, Julio M.

2003-01-01

353

Sub-Angstrom Conformational Changes of a Single Molecule Captured by AFM Variance Analysis  

PubMed Central

A system's equilibrium variance can be analyzed to probe its underlying dynamics at higher resolution. Here, using single-molecule atomic-force microscope techniques, we show how the variance in the length of a single dextran molecule can be used to establish thermodynamic equilibrium and to detect conformational changes not directly observable with other methods. Dextran is comprised of a chain of pyranose rings that each undergoes an Angstrom-scale transition from a chair to boat conformation under a stretching force. Our analysis of the variance of the molecule's fluctuations verifies equilibrium throughout the force-extension curve, consistent with the expected thermodynamic ensemble. This validates further analysis of the variance in the transition region, which reveals an intermediate conformation between the chair and the boat on the sub-Angstrom scale. Our test of thermal equilibrium as well as our variance analysis can be readily extended to a wide variety of molecules, including proteins.

Walther, Kirstin A.; Brujic, Jasna; Li, Hongbin; Fernandez, Julio M.

2006-01-01

354

Conformational behavior of DNA-templated CdS inorganic nanowire  

NASA Astrophysics Data System (ADS)

We describe the conformational behavior and morphological control of DNA-mineralized CdS nanowires in a bulk solution. The conformational behavior of individual double-stranded DNA in the presence of cadmium ions and stoichiometric mixtures of cadmium ions and sulfide ions was directly visualized by fluorescence microscopy. It was found that in the presence of mixtures of cadmium ions and sulfide ions, DNA molecules exhibit a conformational transition from an elongated coil to a compacted state. Mineralized DNA nanowires possess a significant conformational freedom at a microscale, and flexibility in the micro- and nanodimensions. The density of the inorganic material on the nanowire can be controlled by varying the concentrations and the molar ratio of Na2S to Cd(ClO4)2.

Pu, Shengyan; Zinchenko, Anatoly; Murata, Shizuaki

2011-09-01

355

Role of conformational changes in the elution of proteins from reversed-phase HPLC columns.  

PubMed Central

To test the hypothesis that conformational alterations might be involved in the elution of proteins from reversed-phase HPLC columns, the conformations of proteins bound onto a C-8 alkyl-bonded silica surface have been examined in the presence of increasing concentrations of the commonly employed eluent, 1-propanol. Using a combination of photoacoustic, diffuse reflectance deconvolution Fourier transform infrared and front face fluorescence spectroscopic techniques (to minimize interference from light scattering), the existence of surface-associated protein conformational changes induced by propanol is unequivocally demonstrated. The linear relationship found between the amount of propanol needed to elute proteins from C-8 columns and the midpoint of spectrally observed structural transitions is consistent with a role for conformational changes in the elution process.

Katzenstein, G E; Vrona, S A; Wechsler, R J; Steadman, B L; Lewis, R V; Middaugh, C R

1986-01-01

356

Probing messenger RNA conformational heterogeneity using single-molecule fluorescence anisotropy  

NASA Astrophysics Data System (ADS)

In this letter we describe a method to probe biomolecular conformations and their dynamics at the single molecule level. We show, using fluorescence anisotropy based methods, that the hydrodynamic volume of biomolecules captures the intrinsic heterogeneity within a population. Population distributions of conformations and their dynamics are studied by making anisotropy measurements on one molecule at a time within a confocal volume. The mean anisotropy of mRNA is lowered on addition of salt while the spread remains the same. The intrinsic heterogeneity is revealed when conformational transitions are frozen, resulting in a drastic increase in the spread of the anisotropy. These studies reveal that mRNA samples a broad range of conformations.

Sinha, Deepak; Sastry, Srikanth; Shivashankar, G. V.

2006-03-01

357

Coordinate Confusion in Conformal Cosmology  

Microsoft Academic Search

A straight-forward interpretation of standard\\u000aFriedmann-Lemaitre-Robertson-Walker (FLRW) cosmologies is that objects move\\u000aapart due to the expansion of space, and that sufficiently distant galaxies\\u000amust be receding at velocities exceeding the speed of light. Recently, however,\\u000ait has been suggested that a simple transformation into conformal coordinates\\u000acan remove superluminal recession velocities, and hence the concept of the\\u000aexpansion of

Geraint F. Lewis; Matthew J. Francis; Luke A. Barnes; J. Berian James

2007-01-01

358

Fluorescence-coupled CD conformational monitoring of filament formation of tau microtubule-binding repeat domain.  

PubMed

To clarify the contribution of the three- or four-repeated peptide moiety in tau microtubule-binding domain (MBD) to paired helical filament (PHF) formation, conformational transition accompanied by heparin-induced filament formation was investigated stepwise for four repeat peptides (R1-R4), one three-repeated R1-R3-R4 peptide (3RMBD), and one four-repeated R1-R2-R3-R4 peptide (4RMBD) using a combination of thioflavin S fluorescence and circular dichroism (CD) measurements in a neutral buffer (pH 7.6). The comparison of the fluorescence profile of each repeat peptide with those of 3RMBD and 4RMBD showed the synergistic contribution of R1-R4 to PHF formation of MBD. The CD spectrum measured as a function of filament formation time indicates that: (i) two conformational transitions occur for the filament formations of R3 (from the random structure to the beta-sheet structure) and 3RMBD (from the random structure to the alpha-helix structure), (ii) the filament formations of R2 and 4RMBD proceed via the synchronized conformational transitions of the alpha-helix and random structures, and (iii) the filament formation of 4RMBD is dependent on the aggregation behavior of R2. These data are useful for elucidating the MBD conformational transition in tau PHF formation. PMID:16563344

Mizushima, Fumie; Minoura, Katsuhiko; Tomoo, Koji; Sumida, Miho; Taniguchi, Taizo; Ishida, Toshimasa

2006-03-10

359

Conformational stability of Met20 loop of DHFR: A molecular dynamics study  

NASA Astrophysics Data System (ADS)

In the catalytic cycle of dihydrofolate reductase (DHFR), the conformational change of the Met20 loop plays an important role. There are known to be two stable conformations (closed and open states) in the conformational change of the Met20 loop before binding the substrate. However, the conformational stability of these states is still not clear. In this study, we carried out two molecular dynamics simulations corresponding to the closed and open states of DHFR and estimated the free energy of each state of DHFR by using the molecular mechanics-Poisson Bolzmann surface area (MM-PBSA) method. Although the free energy calculations showed the closed state of DHFR was more stable in the solution condition, the difference of free energies between the closed and open state showed the large deviation. This finding shows that the conformational transition between the closed and open state of the Met20 loop could occur frequently under the solution condition. The frequency distributions along the reaction coordinate was calculated to find the possible metastable conformations, indicating that six metastable conformations exist between the closed and open states.

Nishimura, Megumi; Saito, Hiroaki; Kawaguchi, Kazutomo; Nagao, Hidemi

2013-02-01

360

A Measure of Conformational Entropy Change during Thermal Protein Unfolding Using Neutron Spectroscopy  

PubMed Central

Thermal unfolding of proteins at high temperatures is caused by a strong increase of the entropy change which lowers Gibbs free energy change of the unfolding transition (?Gunf = ?H ? T?S). The main contributions to entropy are the conformational entropy of the polypeptide chain itself and ordering of water molecules around hydrophobic side chains of the protein. To elucidate the role of conformational entropy upon thermal unfolding in more detail, conformational dynamics in the time regime of picoseconds was investigated with neutron spectroscopy. Confined internal structural fluctuations were analyzed for ?-amylase in the folded and the unfolded state as a function of temperature. A strong difference in structural fluctuations between the folded and the unfolded state was observed at 30°C, which increased even more with rising temperatures. A simple analytical model was used to quantify the differences of the conformational space explored by the observed protein dynamics for the folded and unfolded state. Conformational entropy changes, calculated on the basis of the applied model, show a significant increase upon heating. In contrast to indirect estimates, which proposed a temperature independent conformational entropy change, the measurements presented here, demonstrated that the conformational entropy change increases with rising temperature and therefore contributes to thermal unfolding.

Fitter, Jorg

2003-01-01

361

Conformal invariance and the conformal-traceless decomposition of the gravitational field  

SciTech Connect

Einstein's theory of general relativity is written in terms of the variables obtained from a conformal-traceless decomposition of the spatial metric and extrinsic curvature. The determinant of the conformal metric is not restricted, so the action functional and equations of motion are invariant under conformal transformations. With this approach the conformal-traceless variables remain free of density weights. The conformal invariance of the equations of motion can be broken by imposing an evolution equation for the determinant of the conformal metric g. Two conditions are considered, one in which g is constant in time and one in which g is constant along the unit normal to the spacelike hypersurfaces. This approach is used to write the Baumgarte-Shapiro-Shibata-Nakamura system of evolution equations in conformally invariant form. The presentation includes a discussion of the conformal thin sandwich construction of gravitational initial data, and the conformal flatness condition as an approximation to the evolution equations.

Brown, J. David [Department of Physics, North Carolina State University, Raleigh, North Carolina 27695 (United States)

2005-05-15

362

Conformational effects on excitonic interactions in a prototypical H-bonded bichromophore: bis(2-hydroxyphenyl)methane.  

PubMed

Laser-induced fluorescence, single-vibronic level fluorescence (SVLF), UV hole burning, and fluorescence dip infrared (FDIR) spectroscopy have been carried out on bis-(2-hydroxyphenyl)methane in order to characterize the ground-state and first excited-state vibronic spectroscopy of this model flexible bichromophore. These studies identified the presence of two conformational isomers. The FDIR spectra in the OH-stretch region determine that conformer A is an OH...O H-bonded conformer, while conformer B is a doubly OH...pi H-bonded conformer with C(2) symmetry. High-resolution ultraviolet spectra ( approximately 50 MHz resolution) of a series of vibronic bands of both conformers confirm and refine these assignments. The transition dipole moment (TDM) direction in conformer A is consistent with electronic excitation that is primarily localized on the donor phenol ring. A tentative assignment of the S(2) origin is made to a set of transitions approximately 400 cm(-1) above S(1). In conformer B, the TDM direction firmly establishes C(2) symmetry for the conformer in its S(1) state and establishes the electronic excitation as delocalized over the two rings, as the lower member of an excitonic pair. The S(2) state has not been clearly identified in the spectrum. Based on CIS calculations, the S(2) state is postulated to be several times weaker than S(1), making it difficult to identify, especially in the midst of overlap from vibronic bands due to conformer A. SVLF spectra show highly unusual vibronic intensity patterns, particularly in conformer B, which cannot be understood by simple harmonic Franck-Condon models, even in the presence of Duschinsky mixing. We postulate that these model flexible bichromophores have TDMs that are extraordinarily sensitive to the distance and orientation of the two aromatic rings, highlighting the need to map out the TDM surface and its dependence on the (up to) five torsional and bending coordinates in order to understand the observations. PMID:19348452

Pillsbury, Nathan R; Müller, Christian W; Meerts, W Leo; Plusquellic, David F; Zwier, Timothy S

2009-04-30

363

Coordinate confusion in conformal cosmology  

NASA Astrophysics Data System (ADS)

A straightforward interpretation of standard Friedmann-Lemaître-Robertson-Walker (FLRW) cosmologies is that objects move apart because of the expansion of space, and that sufficiently distant galaxies must be receding at velocities exceeding the speed of light. Recently, however, it has been suggested that a simple transformation into conformal coordinates can remove superluminal recession velocities, and hence the concept of the expansion of space should be abandoned. This work demonstrates that such conformal transformations do not eliminate superluminal recession velocities for open or flat matter-only FLRW cosmologies, and all possess superluminal expansion. Hence the attack on the concept of the expansion of space based on this is poorly founded. This work concludes by emphasizing that the expansion of space is perfectly valid in the general relativistic framework; however, asking the question of whether space really expands is a futile exercise. Research undertaken as part of the Commonwealth Cosmology Initiative (CCI: http://www.thecci.org), an international collaboration supported by the Australian Research Council. E-mail: gfl@physics.usyd.edu.au

Lewis, Geraint F.; Francis, Matthew J.; Barnes, Luke A.; James, J. Berian

2007-10-01

364

Metrics with Galilean conformal isometry  

SciTech Connect

The Galilean conformal algebra (GCA) arises in taking the nonrelativistic limit of the symmetries of a relativistic conformal field theory in any dimensions. It is known to be infinite dimensional in all spacetime dimensions. In particular, the 2d GCA emerges out of a scaling limit of linear combinations of two copies of the Virasoro algebra. In this paper, we find metrics in dimensions greater than 2 which realize the finite 2d GCA (the global part of the infinite algebra) as their isometry by systematically looking at a construction in terms of cosets of this finite algebra. We list all possible subalgebras consistent with some physical considerations motivated by earlier work in this direction and construct all possible higher-dimensional nondegenerate metrics. We briefly study the properties of the metrics obtained. In the standard one higher-dimensional ''holographic'' setting, we find that the only nondegenerate metric is Minkowskian. In four and five dimensions, we find families of nontrivial metrics with a rather exotic signature. A curious feature of these metrics is that all but one of them are Ricci-scalar flat.

Bagchi, Arjun [School of Mathematics, University of Edinburgh, Edinburgh, EH9 3JZ (United Kingdom); Kundu, Arnab [Theory Group, Department of Physics, University of Texas at Austin, Austin, Texas 78712 (United States)

2011-03-15

365

Three-dimensional Ising model, percolation theory and conformal invariance  

NASA Astrophysics Data System (ADS)

The fractal structure and scaling properties of a 2d slice of the 3d Ising model is studied using Monte Carlo techniques. The percolation transition of geometric spin (GS) clusters is found to occur at the Curie point, reflecting the critical behavior of the 3d model. The fractal dimension and the winding angle statistics of the perimeter and external perimeter of the geometric spin clusters at the critical point suggest that, if conformally invariant in the scaling limit, they can be described by the theory of Schramm-Löwner evolution (SLE?) with diffusivity of ?=5 and 16/5, respectively, putting them in the same universality class as the interfaces in 2d tricritical Ising model. It is also found that the Fortuin-Kasteleyn (FK) clusters associated with the cross-sections undergo a nontrivial percolation transition, in the same universality class as the ordinary 2d critical percolation.

Saberi, A. A.; Dashti-Naserabadi, H.

2010-12-01

366

Use of Chou-Fasman amino acid conformational parameters to analyze the organization of the genetic code and to construct protein genealogies  

Microsoft Academic Search

Summary Chou-Fasman parameters, measuring preferences of each amino acid for different conformational regions in proteins, were used to obtain an amino acid difference index of conformational parameter distance (CPD) values. CPD values were found to be significantly lower for amino acid exchanges representing in the genetic code transitions of purines, G?A than for exchanges representing either transitions of pyrimidines, C?U,

Morris Goodman; G. William Moore

1977-01-01

367

Structural Heterogeneity and Conformational Relaxation in Heme Proteins  

NASA Astrophysics Data System (ADS)

The influence of cooling rate upon the structural heterogeneity of sperm whale myoglobin solutions at cryogenic temperatures was studied. Sample cooling rates were varied by almost four orders of magnitude. FTIR spectra of the CO stretch frequency region reveal that the population of the A states is highly sensitive to the glass transition temperature T_{rm g} of the solvent, which is in turn sensitive to the cooling rate. The structural heterogeneity within each substate was assessed by temperature-derivative spectroscopy (TDS); no significant changes of barrier distributions were found. We conclude that cooling rate plays a negligible role in the structural heterogeneity of protein solutions, and that conformational substates are an intrinsic part of protein systems. Flash photolysis experiments using both O _2 and CO adducts of sperm whale and horse myoglobin reveal an intermediate process that separates geminate and solvent rebinding. This process, named process II, is caused by thermally-induced relaxation (TIR) of the protein from the photoproduct (Mb*) to the deoxy (Mb) configuration. The conformational change Mb* --> Mb was originally modelled as a smooth shift of the rebinding barrier distribution towards higher enthalpies by extrapolation of the spectral position of band III and rebinding enthalpy. Data from light-induced relaxation (LIR) experiments suggest that the relaxation proceeds in discrete steps. A four-well sequential model is proposed in which a conformational change separates the inner two wells.

Chu, Kelvin

368

Conformal invariance in (2+1)-dimensional stochastic systems.  

PubMed

Stochastic partial differential equations can be used to model second-order thermodynamical phase transitions, as well as a number of critical out-of-equilibrium phenomena. In (2+1) dimensions, many of these systems are conjectured (and some are indeed proved) to be described by conformal field theories. We advance, in the framework of the Martin-Siggia-Rose field-theoretical formalism of stochastic dynamics, a general solution of the translation Ward identities, which yields a putative conformal energy-momentum tensor. Even though the computation of energy-momentum correlators is obstructed, in principle, by dimensional reduction issues, these are bypassed by the addition of replicated fields to the original (2+1)-dimensional model. The method is illustrated with an application to the Kardar-Parisi-Zhang (KPZ) model of surface growth. The consistency of the approach is checked by means of a straightforward perturbative analysis of the KPZ ultraviolet region, leading, as expected, to its c=1 conformal fixed point. PMID:20481675

Moriconi, L; Moriconi, M

2010-04-09

369

Conformational diversity in prion protein variants influences intermolecular ?-sheet formation  

PubMed Central

A conformational transition of normal cellular prion protein (PrPC) to its pathogenic form (PrPSc) is believed to be a central event in the transmission of the devastating neurological diseases known as spongiform encephalopathies. The common methionine/valine polymorphism at residue 129 in the PrP influences disease susceptibility and phenotype. We report here seven crystal structures of human PrP variants: three of wild-type (WT) PrP containing V129, and four of the familial variants D178N and F198S, containing either M129 or V129. Comparison of these structures with each other and with previously published WT PrP structures containing M129 revealed that only WT PrPs were found to crystallize as domain-swapped dimers or closed monomers; the four mutant PrPs crystallized as non-swapped dimers. Three of the four mutant PrPs aligned to form intermolecular ?-sheets. Several regions of structural variability were identified, and analysis of their conformations provides an explanation for the structural features, which can influence the formation and conformation of intermolecular ?-sheets involving the M/V129 polymorphic residue.

Lee, Seungjoo; Antony, Lizamma; Hartmann, Rune; Knaus, Karen J; Surewicz, Krystyna; Surewicz, Witold K; Yee, Vivien C

2010-01-01

370

Conformational analysis of a model synthetic prodiginine.  

PubMed

A conformational analysis of a synthetic model prodiginine was carried out. In solution this compound showed a strong preference for the ? conformation, in which all the heterocycles are mutually cis. This conformation provided an ideal alignment of the three N-H groups for interacting with anions when the molecule is protonated. A different conformation was also detected in d(6)-DMSO for the mesylate salt, assigned to the ? conformation, in which the C ring is engaged in an intramolecular hydrogen bond with the OMe group. The formation of a homodimer was observed in concentrated CDCl(3) solutions of the neutral free base form of this prodiginine derivative. DFT calculations and the solid state structures of the hydrochloric and methanesulfonic acid salts were in good agreement with the results observed in solution. A complete study of the relative energies of different tautomers, isomers, and supramolecular complexes supported the preference for the ? conformation both in water and in the gas phase. PMID:22812509

García-Valverde, María; Alfonso, Ignacio; Quiñonero, David; Quesada, Roberto

2012-07-19

371

Biological Function of the Low-pH, Fusion-Inactive Conformation of Rabies Virus Glycoprotein (G): G Is Transported in a Fusion-Inactive State-Like Conformation  

Microsoft Academic Search

The glycoprotein (G) of rabies virus can assume at least three different conformations: the native (N) state detected at the viral surface above pH 7; the activated (A) hydrophobic state, which is probably involved in the firststepsofthefusionprocess;andthefusion-inactive(I)conformation.ThereisapH-dependentequilibrium between these states, the equilibrium being shifted towards the I state at low pH. It has been supposed that the transition from the

YVES GAUDIN; CHRISTINE TUFFEREAU; PETER DURRER; ANNE FLAMAND; ANDROB W. H. RUIGROK

1995-01-01

372

Anticholinergic substances: A single consistent conformation  

PubMed Central

An interactive computer-graphics analysis of 24 antagonists of acetylcholine at peripheral autonomic post-ganglionic (muscarinic) nervous junctions and at similar junctions in the central nervous system, the crystal structures of which are known, has led to the determination of a single, consistent, energetically favorable conformation for all 24 substances, although their observed crystal structure conformations vary widely. The absolute configuration and the single, consistent (ideal) conformation of the chemical groups required for maximum anticholinergic activity are described quantitatively. Images

Pauling, Peter; Datta, Narayandas

1980-01-01

373

Anticholinergic substances: A single consistent conformation.  

PubMed

An interactive computer-graphics analysis of 24 antagonists of acetylcholine at peripheral autonomic post-ganglionic (muscarinic) nervous junctions and at similar junctions in the central nervous system, the crystal structures of which are known, has led to the determination of a single, consistent, energetically favorable conformation for all 24 substances, although their observed crystal structure conformations vary widely. The absolute configuration and the single, consistent (ideal) conformation of the chemical groups required for maximum anticholinergic activity are described quantitatively. PMID:16592775

Pauling, P; Datta, N

1980-02-01

374

3D Conformal External-Beam Technique  

Microsoft Academic Search

Three-dimensional conformal external-beam accelerated partial breast irradiation (3D-conformal APBI) allows noninvasive delivery\\u000a of hypofractionated adjuvant radiation treatment to the region of the breast at highest risk of developing a local recurrence\\u000a after lumpectomy. The potential advantages of a 3D conformal radiation therapy approach to APBI compared to brachytherapy\\u000a include its noninvasive approach and an improvement in dose homogeneity, while a

Yasmin Hasan; Frank A. Vicini

375

Novel Conformation of an RNA Structural Switch  

PubMed Central

The RNA duplex, (5?GACGAGUGUCA)2, has two conformations in equilibrium. The nuclear magnetic resonance solution structure reveals that the major conformation of the loop, 5?GAGU/3?UGAG, is novel and contains two unusual Watson–Crick/Hoogsteen GG pairs with G residues in the syn conformation, two A residues stacked on each other in the center of the helix with inverted sugars, and two bulged-out U residues. The structure provides a benchmark for testing approaches for predicting local RNA structure and a sequence that allows the design of a unique arrangement of functional groups and/or a conformational switch into nucleic acids.

2012-01-01

376

Rotational Spectroscopy Unveils Eleven Conformers of Adrenaline  

NASA Astrophysics Data System (ADS)

Recent improvements in our LA-MB-FTMW instrumentation have allowed the characterization of eleven and eight conformers for the neurotransmitters adrenaline and noradrenaline respectively. The observation of this rich conformational behavior is in accordance with the recent observation of seven conformers for dopamine and in sharp contrast with the conformational reduction proposed for catecholamines. C. Cabezas, I. Peña, J. C. López, J. L. Alonso J. Phys. Chem. Lett. 2013, 4, 486. H. Mitsuda, M. Miyazaki, I. B. Nielsen, P. Carcabal,C. Dedonder, C. Jouvet, S. Ishiuchi, M. Fujii J. Phys. Chem. Lett. 2010, 1, 1130.

Cabezas, C.; Cortijo, V.; Mata, S.; Lopez, J. C.; Alonso, J. L.

2013-06-01

377

Quantum charge transport and conformational dynamics of macromolecules.  

PubMed

We study the dynamics of quantum excitations inside macromolecules which can undergo conformational transitions. In the first part of the paper, we use the path integral formalism to rigorously derive a set of coupled equations of motion which simultaneously describe the molecular and quantum transport dynamics, and obey the fluctuation/dissipation relationship. We also introduce an algorithm which yields the most probable molecular and quantum transport pathways in rare, thermally activated reactions. In the second part of the paper, we apply this formalism to simulate the propagation of a quantum charge during the collapse of a polymer from an initial stretched conformation to a final globular state. We find that the charge dynamics is quenched when the chain reaches a molten globule state. Using random matrix theory we show that this transition is due to an increase of quantum localization driven by dynamical disorder. We argue that collapsing conducting polymers may represent a physical realization of quantum small-world networks with dynamical rewiring probability. PMID:22697534

Boninsegna, L; Faccioli, P

2012-06-01

378

Transition metals  

PubMed Central

Transition metals such as Iron (Fe) and Copper (Cu) are essential for plant cell development. At the same time, due their capability to generate hydroxyl radicals they can be potentially toxic to plant metabolism. Recent works on hydroxyl-radical activation of ion transporters suggest that hydroxyl radicals generated by transition metals could play an important role in plant growth and adaptation to imbalanced environments. In this mini-review, the relation between transition metals uptake and utilization and oxidative stress-activated ion transport in plant cells is analyzed, and a new model depicting both apoplastic and cytosolic mode of ROS signaling to plasma membrane transporters is suggested.

Rodrigo-Moreno, Ana; Poschenrieder, Charlotte; Shabala, Sergey

2013-01-01

379

Approaching Conformality with Ten Flavors  

SciTech Connect

We present first results for lattice simulations, on a single volume, of the low-lying spectrum of an SU(3) Yang-Mills gauge theory with N{sub f} = 10 light fermions in the fundamental representation. Fits to the fermion mass dependence of various observables are found to be globally consistent with the hypothesis that this theory is within or just outside the strongly-coupled edge of the conformal window, with mass anomalous dimension {gamma}* {approx} 1 over the range of scales simulated. We stress that we cannot rule out the possibility of spontaneous chiral-symmetry breaking at scales well below our infrared cutoff. We discuss important systematic effects, including finite-volume corrections, and consider directions for future improvement.

Appelquist, Thomas; Brower, Richard C.; Buchoff, Michael I.; Cheng, Michael; Cohen, Saul D.; Fleming, George T.; Kiskis, Joe; Lin, Meifeng; Na, Heechang; Neil, Ethan T.; Osborn, James C.

2012-04-01

380

Technidilaton at the conformal edge  

NASA Astrophysics Data System (ADS)

Technidilaton (TD) was proposed long ago in the technicolor near criticality/conformality. To reveal the critical behavior of TD, we explicitly compute the nonperturbative contributions to the scale anomaly ????? and to the technigluon condensate ??G??2?, which are generated by the dynamical mass m of the technifermions. Our computation is based on the (improved) ladder Schwinger-Dyson equation, with the gauge coupling ? replaced by the two-loop running coupling ?(?) having the Caswell-Banks-Zaks infrared fixed point ?*: ?(?)??=?* for the infrared region mconformal edge”). Our result precisely reproduces the formal identity ?????=(?(?)/4?2)??G??2?, where ?(?)=?TC(??)/(??TC)=-(2?cr/?)·(?/?cr-1)3/2 is the nonperturbative beta function corresponding to the above essential singularity scaling of m/?TC. Accordingly, the partially conserved dilatation current implies (MTD/m)2(FTD/m)2=-4?????/m4?const?0 at criticality limit, where MTD is the mass of TD and FTD the decay constant of TD. We thus conclude that at criticality limit the TD could become a “true (massless) Nambu-Goldstone boson” MTD/m?0, only when m/FTD?0, namely, getting decoupled, as was the case of “holographic technidilaton” of Haba-Matsuzaki-Yamawaki. The decoupled TD can be a candidate of dark matter.

Hashimoto, Michio; Yamawaki, Koichi

2011-01-01

381

Localized structural fluctuations promote amyloidogenic conformations in transthyretin.  

PubMed

The process of transthyretin (TTR) misfolding and aggregation, including amyloid formation, appears to cause a number of degenerative diseases. During amyloid formation, the native protein undergoes a tetramer-to-folded monomer transition, followed by local unfolding of the monomer to an assembly-competent amyloidogenic intermediate. Here we use NMR relaxation dispersion to probe conformational exchange at physiological pH between native monomeric TTR (the F87M/L110M variant) and a small population of a transiently formed amyloidogenic intermediate. The dispersion experiments show that a majority of the residues in the ?-sheet containing ?-strands D, A, G, and H undergo conformational fluctuations on microsecond-to-millisecond timescales. Exchange broadening is greatest for residues in the outer ?-strand H, which hydrogen bonds to ?-strand H' of a neighboring subunit in the tetramer, but the associated structural fluctuations propagate across the entire ?-sheet. Fluctuations in the other ?-sheet are limited to the outer ?-strand F, which packs against strand F' in the tetramer, while the B, C, and E ?-strands of this sheet remain stable. The structural changes were also investigated under more forcing amyloidogenic conditions (pH6.4-3.7), where ?-strand D and regions of the D-E and E-F loops were additionally destabilized, increasing the population of the amyloidogenic intermediate and accelerating amyloid formation. Strands B, C, and E appear to maintain native-like conformations in the partially unfolded, amyloidogenic state of wild-type TTR. In the case of the protective mutant T119M, the conformational fluctuations are suppressed under both physiological and mildly acidic conditions, indicating that the dynamic properties of TTR correlate well with its aggregation propensity. PMID:23318953

Lim, Kwang Hun; Dyson, H Jane; Kelly, Jeffery W; Wright, Peter E

2013-01-11

382

Asymmetric Conformational Flexibility in the ATP-Binding Cassette Transporter HI1470/1  

PubMed Central

Putative metal-chelate-type ABC transporter HI1470/1 is homologous with vitamin B12 importer BtuCD but exhibits a distinct inward-facing conformation in contrast to the outward-facing conformation of BtuCD. Normal-mode analysis of HI1470/1 reveals the intrinsic asymmetric conformational flexibility in this transporter and demonstrates that the transition from the inward-facing to the outward-facing conformation is realized through the asymmetric motion of individual subunits of the transporter. This analysis suggests that the asymmetric arrangement of the BtuC dimer in the crystal structure of the BtuCD-F complex represents an intermediate state relating HI1470/1 and BtuCD. Furthermore, a twisting motion between transmembrane domains and nucleotide-binding domains encoded in the lowest-frequency normal mode of this type of importer is found to contribute to the conformational transitions during the whole cycle of substrate transportation. A more complete translocation mechanism of the BtuCD type importer is proposed.

Weng, Jingwei; Ma, Jianpeng; Fan, Kangnian; Wang, Wenning

2009-01-01

383

Reconciling mediating and slaving roles of water in protein conformational dynamics.  

PubMed

Proteins accomplish their physiological functions with remarkably organized dynamic transitions among a hierarchical network of conformational substates. Despite the essential contribution of water molecules in shaping functionally important protein dynamics, their exact role is still controversial. Water molecules were reported either as mediators that facilitate or as masters that slave protein dynamics. Since dynamic behaviour of a given protein is ultimately determined by the underlying energy landscape, we systematically analysed protein self energies and protein-water interaction energies obtained from extensive molecular dynamics simulation trajectories of barstar. We found that protein-water interaction energy plays the dominant role when compared with protein self energy, and these two energy terms on average have negative correlation that increases with increasingly longer time scales ranging from 10 femtoseconds to 100 nanoseconds. Water molecules effectively roughen potential energy surface of proteins in the majority part of observed conformational space and smooth in the remaining part. These findings support a scenario wherein water on average slave protein conformational dynamics but facilitate a fraction of transitions among different conformational substates, and reconcile the controversy on the facilitating and slaving roles of water molecules in protein conformational dynamics. PMID:23593243

Zhao, Li; Li, Wenzhao; Tian, Pu

2013-04-11

384

Structure and conformational stability of protonated dialanine.  

PubMed

A systematic investigation on the structure and stability of the four conformers of the protonated dialanine cation (transA1, transA2, transO1, cisA3) was performed employing the HF, MP2, and hybrid DFT methods with various basis sets which ranged from the 6-31G* to the basis set larger than the correlation consistent aug-cc-pVTZ basis set. It is found that the backbone dihedral angles and energies of the conformers are sensitive to the electron correlation level and basis set, especially manifesting slow convergence of conformer structure and energetics with basis set at the MP2 level. At the MP2 basis set limit corrected by CCSD(T) correlation effect, the lowest transA1 conformer is almost isoenergetic with the cisA3 conformer, followed by the transA2 conformer ( approximately 0.5 kcal/mol above transA1), and, last, the transO1 conformer ( approximately 1.2 kcal/mol above transA1). Vibrational and thermal (entropic) factors appear to have an important effect on the relative stability between conformers at room temperature, reducing the energy difference between transA1 and transA2 conformers and making cisA3 higher in energy than transA1 or transA2, which is in accord with the recent infrared multiphoton dissociation experimental data on this cation. According to the polarizable continuum model calculations, solvation of protonated dialanine in water would significantly enhance the stability of the transA2 conformer, making it most populated in aqueous solution at room temperature. Among the tested hybrid DFT methods in this study, B3LYP/6-31G* was found to be the most effective for predicting the conformational structures and relevant stability of protonated dialanine cation in the gas phase. PMID:20572657

Sohn, Woon Yong; Lee, Jae Shin

2010-07-22

385

Conformation of 2-aminofluorene-modified DNA  

SciTech Connect

Minimized potential-energy calculations were performed to determine the conformation of the 2-aminofluorene (AF) adduct to dCpdG at guanine C-8. The AF adduct has many low-energy conformers in both the anti and the syn domains of the guanine. This is in contrast with the acetylated adduct, (AAF), which greatly prefers the syn domain. Two types of low-energy guanine anti-conformations were obtained: (1) conformers that preserve guanine-cytidine stacking and (2) conformers with fluorene-cytidine stacking. Of special importance are conformers with omega,omega,phi = g/sup -/,g/sup -/,g/sup +/, characteristic of normal A- or B-helices, which are found in both groups. No conformers of this type were obtained for the acetylated AAF adduct. The guanine-cytidine stacked form with this conformation can be incorporated in the B-helix without any distortion, with the carcinogen situated at the helix exterior. The fluorene in this model can slide into the helix to yield a fluorene-cytidine stacked minimum-energy conformation. This requires no denaturation, although one base pair is unstacked and the helix axis is bent. Low-energy syn-conformations, similar to those obtained for the AAF adduct, were also computed. These were either guanine-cytidine stacked or fluorene-cytidine stacked. The syn forms are less likely to be observed in larger DNA polymers of the AF adduct, since they cause more distortion than the anti-conformations. However, they might well be observed in crystals of small subunits, and they should contribute significantly to the population in solution. 56 references, 10 figures, 5 tables.

Broyde, S.; Hingerty, B.

1983-01-01

386

Conformal energy, conformal Laplacian, and energy measures on the Sierpinski gasket  

Microsoft Academic Search

On the Sierpinski Gasket (SG) and related fractals, we define a notion of conformal energy E' and conformal Laplacian ' for a given conformal factor ', based on the corresponding notions in Riemannian geometry in dimension n 6= 2. We derive a differential equation that describes the dependence of the effective resistances of E' on '. We show that the

Jonas Azzam; Michael A. Hall; Robert S. Strichartz

2007-01-01

387

Computational Studies of the Farnesyltransferase Ternary Complex Part II: The Conformational Activation of Farnesyldiphosphate†  

PubMed Central

Studies aimed at elucidating the reaction mechanism of farnesyltransferase (FTase), which catalyzes the prenylation of many cellular signaling proteins including Ras, has been an active area of research. Much is known regarding substrate binding and the impact of various catalytic site residues on catalysis. However, the molecular-level details regarding the conformational rearrangement of farnesyldiphosphate (FPP), which has been proposed via structural analysis and mutagenesis studies to occur prior to the chemical step, is still poorly understood. Following on our previous computational characterization of the resting state of the FTase ternary complex, the thermodynamics of the conformational rearrangement step in the absence of magnesium was investigated for the wild type FTase and the Y300F? mutant complexed with the peptide CVIM. In addition, we also explored the target dependence of the conformational activation step by perturbing isoleucine into a leucine (CVLM). The calculated free energy profiles of the proposed conformational transition confirm the presence of a stable intermediate state, which was identified only when the diphosphate is monoprotonated (FPP2?). The farnesyl group in the computed intermediate state assumes a conformation similar to that of the product complex, particularly for the first two isoprene units. We found that Y300? can readily form hydrogen bonds with either of the phosphates of FPP. Removing the hydroxyl group on Y300? does not significantly alter the thermodynamics of the conformational transition, but shifts the location of the intermediate farther away from the nucleophile by 0.5Å, which suggests that Y300? facilitate the reaction by stabilizing the chemical step. Our results also showed an increased transition barrier height for CVLM (1.5 kcal/mol higher than that of CVIM). Although qualitatively consistent with the findings from the recent kinetic isotope experiments by Fierke and coworkers, the magnitude is not large enough to affect the rate limiting step.

Cui, Guanglei; Merz, Kenneth M.

2008-01-01

388

Conformal Higgs, or Techni-Dilaton -- Composite Higgs Near Conformality  

NASA Astrophysics Data System (ADS)

In contrast to the folklore that Technicolor (TC) is a "Higgsless theory", we shall discuss existence of a composite Higgs boson, Techni-Dilaton (TD), a pseudo-Nambu-Goldstone boson of the scale invariance in the Scale-invariant/Walking/Conformal TC (SWC TC) which generates a large anomalous dimension ?m ? 1 in a wide region from the dynamical mass m = {O} ({TeV}) of the techni-fermion all the way up to the intrinsic scale ?TC of the SWC TC (analogue of ?QCD), where ?TC is taken typically as the scale of the Extended TC scale ?ETC: ?TC ? ?ETC 103 TeV (? m). All the techni-hadrons have mass on the same order {O}(m), which in SWC TC is extremely smaller than the intrinsic scale ?TC ? ?ETC, in sharp contrast to QCD where both are of the same order. The mass of TD arises from the non-perturbative scale anomaly associated with the techni-fermion mass generation and is typically 500-600 GeV, even smaller than other techni-hadrons of the same order of {O}(m), in another contrast to QCD which is believed to have no scalar bar qq bound state lighter than other hadrons. We discuss the TD mass in various methods, Gauged NJL model via ladder Schwinger-Dyson (SD) equation, straightforward calculations in the ladder SD/ Bethe-Salpeter equation, and the holographic approach including techni-gluon condensate. The TD may be discovered in LHC.

Yamawaki, Koichi

2011-01-01

389

Sex Roles, Task Competence, and Conformity  

Microsoft Academic Search

The purpose of the investigation was to determine the relative importance of sex roles and task competence as regards the relationship between sex and conformity.The Ss in Study I were 68 American students; half were male, and the other half female. The Ss were tested by means of a Conformity Instrument and a Masculinity-Femininity scale. The results show that task

Carlos Goldberg

1974-01-01

390

Conformance testing to space communication network  

NASA Astrophysics Data System (ADS)

Space Internet technology is the Internet that refers to technology which is widely used in the terrestrial network, improved under the space communications feature, thus using the improved Internet protocols and technology, to meet the needs of future space mission technology. In protocol engineering area, conformance testing is a very important step. The purpose of conformance testing is to determine to what extent a single implementation of a particular standard conforms to the individual requirements of that standard. Conformance testing can increase the confidence level of implementation complying with the protocol specification, and enhance the probability of interoperability between different implementation. The ISO/IEC9646 standard described by ISO is the maturest theory in protocol conformance testing theories. Space communication network test framework is proposed, in which the test architecture is defined for conformance testing to space communication network. In this paper, the ISO9646 standard is improved, in order to meet the requirements of conformance testing of space communication network. The contribution of this paper is the proposition of a complete method to the design of conformance testing against space communication network. The simulation results have shown that the method has better test results, to meet the space communications network testing needs. With the testing of the space communications network protocol implementation, we discovered the problems of the protocol implementation. It has verified the theory and method.

Xie, Lei; Wei, Jiaolong; Zhu, Guangxi

2007-11-01

391

Temperature corrections to conformal field theory  

Microsoft Academic Search

We consider finite temperature dynamical correlation functions in the interacting delta-function Bose gas. In the low-temperature limit the asymptotic behaviour of correlation functions can be determined from conformal field theory. In the present work we determine the deviations from conformal behaviour at low temperatures.

F. H. L. Eßler; V. E. Korepin; F. T. Latrémolière

1998-01-01

392

Temperature corrections to conformal field theory  

Microsoft Academic Search

:   We consider finite temperature dynamical correlation functions in the interacting delta-function Bose gas. In the low-temperature\\u000a limit the asymptotic behaviour of correlation functions can be determined from conformal field theory. In the present work\\u000a we determine the deviations from conformal behaviour at low temperatures.

F. H. L. Eßler; Vladimir E. Korepin; F. T. Latrémolière

1998-01-01

393

Unexpected conformational behavior of gaseous 1-pentyne  

NASA Astrophysics Data System (ADS)

The molecular structure and conformations of 1-pentyne have been studied experimentally by the gas electron diffraction method. A conformational mixture of 68.6% gauche and 31.4% anti, with standard deviation equal to 4.5%, was observed. Results from ab initio MP2/6-31G? optimization calculations are in excellent agreement with those observed.

Traetteberg, M.; Bakken, P.; Hopf, H.

1999-10-01

394

Conformational readout of RNA by small ligands.  

PubMed

RNA molecules have highly versatile structures that can fold into myriad conformations, providing many potential pockets for binding small molecules. The increasing number of available RNA structures, in complex with proteins, small ligands and in free form, enables the design of new therapeutically useful RNA-binding ligands. Here we studied RNA ligand complexes from 10 RNA groups extracted from the protein data bank (PDB), including adaptive and non-adaptive complexes. We analyzed the chemical, physical, structural and conformational properties of binding pockets around the ligand. Comparing the properties of ligand-binding pockets to the properties of computed pockets extracted from all available RNA structures and RNA-protein interfaces, revealed that ligand-binding pockets, mainly the adaptive pockets, are characterized by unique properties, specifically enriched in rare conformations of the nucleobase and the sugar pucker. Further, we demonstrate that nucleotides possessing the rare conformations are preferentially involved in direct interactions with the ligand. Overall, based on our comprehensive analysis of RNA-ligand complexes, we suggest that the unique conformations adopted by RNA nucleotides play an important role in RNA recognition by small ligands. We term the recognition of a binding site by a ligand via the unique RNA conformations "RNA conformational readout." We propose that "conformational readout" is a general way by which RNA binding pockets are recognized and selected from an ensemble of different RNA states. PMID:23618839

Kligun, Efrat; Mandel-Gutfreund, Yael

2013-04-16

395

Conformal invariance, supersymmetry and string theory  

Microsoft Academic Search

Covariant quantization of string theories is developed in the context of conformal field theory and the BRST quantization procedure. The BRST method is used to covariantly quantize superstrings, and in particular to construct the vertex operators for string emission as well as the supersymmetry charge. The calculation of string loop diagrams is sketched. We discuss how conformal methods can be

Daniel Friedan; Emil Martinec; Stephen Shenker

1986-01-01

396

Topics in conformally compact Einstein metrics  

Microsoft Academic Search

We discuss a number of topics in the area of conformally compact Einstein\\u000ametrics, mostly centered around the global existence question of finding such\\u000ametrics with an arbitrarily prescribed conformal infinity. The paper is partly\\u000aa survey of this area but also presents new results and a number of open\\u000aproblems.

Michael T. Anderson

2005-01-01

397

Conformity and Integration of Software Processes1  

Microsoft Academic Search

In this paper we present a systematic approach fo r the determination of process conformity and the integration of process models. Similar to CMM w hich defines consecutive levels of process maturity , we propose a five-level model measuring the conform ity of process models. The approach is of practical importance for a number of applications, e.g. when a company's

Ruth Breu; Walter Huber; Wolfgang Schwerin

398

Conformational Sampling of Peptides in Cellular Environments?  

PubMed Central

Abstract Biological systems provide a complex environment that can be understood in terms of its dielectric properties. High concentrations of macromolecules and cosolvents effectively reduce the dielectric constant of cellular environments, thereby affecting the conformational sampling of biomolecules. To examine this effect in more detail, the conformational preference of alanine dipeptide, poly-alanine, and melittin in different dielectric environments is studied with computer simulations based on recently developed generalized Born methodology. Results from these simulations suggest that extended conformations are favored over ?-helical conformations at the dipeptide level at and below dielectric constants of 5–10. Furthermore, lower-dielectric environments begin to significantly stabilize helical structures in poly-alanine at ? = 20. In the more complex peptide melittin, different dielectric environments shift the equilibrium between two main conformations: a nearly fully extended helix that is most stable in low dielectrics and a compact, V-shaped conformation consisting of two helices that is preferred in higher dielectric environments. An additional conformation is only found to be significantly populated at intermediate dielectric constants. Good agreement with previous studies of different peptides in specific, less-polar solvent environments, suggest that helix stabilization and shifts in conformational preferences in such environments are primarily due to a reduced dielectric environment rather than specific molecular details. The findings presented here make predictions of how peptide sampling may be altered in dense cellular environments with reduced dielectric response.

Tanizaki, Seiichiro; Clifford, Jacob; Connelly, Brian D.; Feig, Michael

2008-01-01

399

Implementation of WPDL Conforming Workflow Model  

Microsoft Academic Search

Workflow Process Definition Language (WPDL) facilitates the transfer of workflow process definitions between separate workflow products. However, much work is still needed to transfer the specific workflow model to a WPDL conforming model. CIMFlow is a workflow management system developed by the National CIMS Engineering Research Center. This paper discusses the methods by which the CIMFlow model conforms to the

ZHANG Zhijun

400

Regulatory Conformance Checking: Logic and Logical Form  

ERIC Educational Resources Information Center

|We consider the problem of checking whether an organization conforms to a body of regulation. Conformance is studied in a runtime verification setting. The regulation is translated to a logic, from which we synthesize monitors. The monitors are evaluated as the state of an organization evolves over time, raising an alarm if a violation is…

Dinesh, Nikhil

2010-01-01

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