Página 1 dos resultados de 116 itens digitais encontrados em 0.039 segundos

Implementations of Nosé–Hoover and Nosé–Poincaré thermostats in mesoscopic dynamic simulations with the united-residue model of a polypeptide chain

Kleinerman, Dana S.; Czaplewski, Cezary; Liwo, Adam; Scheraga, Harold A.
Fonte: American Institute of Physics Publicador: American Institute of Physics
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
903.3638%
Molecular dynamics (MD) simulations generate a canonical ensemble only when integration of the equations of motion is coupled to a thermostat. Three extended phase space thermostats, one version of Nosé–Hoover and two versions of Nosé–Poincaré, are compared with each other and with the Berendsen thermostat and Langevin stochastic dynamics. Implementation of extended phase space thermostats was first tested on a model Lennard-Jones fluid system; subsequently, they were implemented with our physics-based protein united-residue (UNRES) force field MD. The thermostats were also implemented and tested for the multiple-time-step reversible reference system propagator (RESPA). The velocity and temperature distributions were analyzed to confirm that the proper canonical distribution is generated by each simulation. The value of the artificial mass constant, Q, of the thermostat has a large influence on the distribution of the temperatures sampled during UNRES simulations (the velocity distributions were affected only slightly). The numerical stabilities of all three algorithms were compared with each other and with that of microcanonical MD. Both Nosé–Poincaré thermostats, which are symplectic, were not very stable for both the Lennard-Jones fluid and UNRES MD simulations started from nonequilibrated structures which implies major changes of the potential energy throughout a trajectory. Even though the Nosé–Hoover thermostat does not have a canonical symplectic structure...

An efficient and accurate molecular alignment and docking technique using ab initio quality scoring

Füsti-Molnár, László; Merz, Kenneth M.
Fonte: American Institute of Physics Publicador: American Institute of Physics
Tipo: Artigo de Revista Científica
EN
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910.84%
An accurate and efficient molecular alignment technique is presented based on first principle electronic structure calculations. This new scheme maximizes quantum similarity matrices in the relative orientation of the molecules and uses Fourier transform techniques for two purposes. First, building up the numerical representation of true ab initio electronic densities and their Coulomb potentials is accelerated by the previously described Fourier transform Coulomb method. Second, the Fourier convolution technique is applied for accelerating optimizations in the translational coordinates. In order to avoid any interpolation error, the necessary analytical formulas are derived for the transformation of the ab initio wavefunctions in rotational coordinates. The results of our first implementation for a small test set are analyzed in detail and compared with published results of the literature. A new way of refinement of existing shape based alignments is also proposed by using Fourier convolutions of ab initio or other approximate electron densities. This new alignment technique is generally applicable for overlap, Coulomb, kinetic energy, etc., quantum similarity measures and can be extended to a genuine docking solution with ab initio scoring.

An analytical approach to computing biomolecular electrostatic potential. I. Derivation and analysis

Fenley, Andrew T.; Gordon, John C.; Onufriev, Alexey
Fonte: American Institute of Physics Publicador: American Institute of Physics
Tipo: Artigo de Revista Científica
EN
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910.84%
Analytical approximations to fundamental equations of continuum electrostatics on simple shapes can lead to computationally inexpensive prescriptions for calculating electrostatic properties of realistic molecules. Here, we derive a closed-form analytical approximation to the Poisson equation for an arbitrary distribution of point charges and a spherical dielectric boundary. The simple, parameter-free formula defines continuous electrostatic potential everywhere in space and is obtained from the exact infinite-series (Kirkwood) solution by an approximate summation method that avoids truncating the infinite series. We show that keeping all the terms proves critical for the accuracy of this approximation, which is fully controllable for the sphere. The accuracy is assessed by comparisons with the exact solution for two unit charges placed inside a spherical boundary separating the solute of dielectric 1 and the solvent of dielectric 80. The largest errors occur when the source charges are closest to the dielectric boundary and the test charge is closest to either of the sources. For the source charges placed within 2 Å from the boundary, and the test surface located on the boundary, the root-mean-square error of the approximate potential is less than 0.1 kcal∕mol∕∣e∣ (per unit test charge). The maximum error is 0.4 kcal∕mol∕∣e∣. These results correspond to the simplest first-order formula. A strategy for adopting the proposed method for realistic biomolecular shapes is detailed. An extensive testing and performance analysis on real molecular structures are described in Part II that immediately follows this work as a separate publication. Part II also contains an application example.

Simulations of nucleation and elongation of amyloid fibrils

Zhang, Jianing; Muthukumar, M.
Fonte: American Institute of Physics Publicador: American Institute of Physics
Tipo: Artigo de Revista Científica
EN
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We present a coarse-grained model for the growth kinetics of amyloid fibrils from solutions of peptides and address the fundamental mechanism of nucleation and elongation by using a lattice Monte Carlo procedure. We reproduce the three main characteristics of nucleation of amyloid fibrils: (1) existence of lag time, (2) occurrence of a critical concentration, and (3) seeding. We find the nucleation of amyloid fibrils to require a quasi-two-dimensional configuration, where a second layer of β sheet must be formed adjunct to a first layer, which in turn leads to a highly cooperative nucleation barrier. The elongation stage is found to involve the Ostwald ripening (evaporation-condensation) mechanism, whereby bigger fibrils grow at the expense of smaller ones. This new mechanism reconciles the debate as to whether protofibrils are precursors or monomer reservoirs. We have systematically investigated the roles of time, peptide concentration, temperature, and seed size. In general, we find that there are two kinds of lag time arising from two different mechanisms. For higher temperatures or low enough concentrations close to the disassembly boundary, the fibrillization follows the nucleation mechanism. However, for low temperatures, where the nucleation time is sufficiently short...

Dielectric relaxation of cytochrome c oxidase: Comparison of the microscopic and continuum models

Leontyev, I. V.; Stuchebrukhov, A. A.
Fonte: American Institute of Physics Publicador: American Institute of Physics
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
903.3638%
We have studied a charge-insertion process that models the deprotonation of a histidine side chain in the active site of cytochrome c oxidase (CcO) using both the continuum electrostatic calculations and the microscopic simulations. The group of interest is a ligand to CuB center of CcO, which has been previously suggested to play the role of the proton pumping element in the enzyme; the group is located near a large internal water cavity in the protein. Using the nonpolarizable Amber-99 force field in molecular dynamics (MD) simulations, we have calculated the nuclear part of the reaction-field energy of charging of the His group and combined it with the electronic part, which we estimated in terms of the electronic continuum (EC) model, to obtain the total reaction-field energy of charging. The total free energy obtained in this MDEC approach was then compared with that calculated using pure continuum electrostatic model with variable dielectric parameters. The dielectric constant for the “dry” protein and that of the internal water cavity of CcO were determined as those parameters that provide best agreement between the continuum and microscopic MDEC model. The nuclear (MD) polarization alone (without electronic part) of a dry protein was found to correspond to an unphysically low dielectric constant of only about 1.3...

Further analysis and comparative study of intermolecular interactions using dimers from the S22 database

Molnar, Laszlo Fusti; He, Xiao; Wang, Bing; Merz, Kenneth M.
Fonte: American Institute of Physics Publicador: American Institute of Physics
Tipo: Artigo de Revista Científica
EN
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Accurate MP2 and CCSD(T) complete basis set (CBS) interaction energy curves (14 points for each curve) have been obtained for 20 of the dimers reported in the S22 set and analytical Morse curves have been fitted that can be used in developing updated density functional theory (DFT) and force field models. The magnitude and the effect of the basis set superposition error (BSSE) were carefully investigated. We found that going up to aug-cc-pVDZ and aug-cc-pVTZ basis sets is enough to obtain accurate CBS MP2 energies when BSSE corrected values are used but aug-cc-pVTZ and aug-cc-pVQZ basis sets are needed when the BSSE uncorrected total energies are used in CBS extrapolations. MP2 interaction energies with smaller basis sets such as 6-31G* are found to have very little dispersion energy and that the true source of dispersion attributed attractive interactions is almost entirely due to BSSE. MP2 and CCSD(T) CBS interaction energies are found to be very close to one another if aromatic systems are not involved. Comparative analyses have been performed with semiempirical and ab initio methods utilizing the moderate in size but affordable 6-31G* basis set both of which can be readily applied to macromolecular systems. The new M06-2X and M06-L DFT functionals were found to be more accurate than all methods tested herein. Interaction energy curves using the SG1 grid showed discontinuities for several of the dimer systems but this problem disappeared when finer DFT numerical grids were used.

Measuring distances within unfolded biopolymers using fluorescence resonance energy transfer: The effect of polymer chain dynamics on the observed fluorescence resonance energy transfer efficiency

Makarov, Dmitrii E.; Plaxco, Kevin W.
Fonte: American Institute of Physics Publicador: American Institute of Physics
Tipo: Artigo de Revista Científica
EN
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925.36984%
Recent years have seen a number of investigations in which distances within unfolded proteins, polypeptides, and other biopolymers are probed via fluorescence resonance energy transfer, a method that relies on the strong distance dependence of energy transfer between a pair of dyes attached to the molecule of interest. In order to interpret the results of such experiments it is commonly assumed that intramolecular diffusion is negligible during the excited state lifetime. Here we explore the conditions under which this “frozen chain” approximation fails, leading to significantly underestimated donor-acceptor distances, and describe a means of correcting for polymer dynamics in order to estimate these distances more accurately.

Structure and thermodynamics of colloidal protein cluster formation: Comparison of square-well and simple dipolar models

Young, Teresa M.; Roberts, Christopher J.
Fonte: American Institute of Physics Publicador: American Institute of Physics
Tipo: Artigo de Revista Científica
EN
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908.7482%
Reversible formation of weakly associated protein oligomers or clusters is a key early step in processes such as protein aggregation and colloidal phase separation. A previously developed cell-based, quasichemical model for lattice fluids [T. M. Young and C. J. Roberts, J. Chem. Phys. 127, 165101 (2007)] is extended here to treat continuous-space systems. It is illustrated using two simplified limiting cases for globular proteins at the isoelectric point: spherical square-well (SW) particles with an isotropic short-ranged attraction and screened dipolar particles with SW attractions and square-shoulder repulsions. Cluster free energies (ΔAi) and structures are analyzed as a function of the reduced second virial coefficient b2∗. ΔAi values and the average structures of clusters up to pentamers have distinct differences due to the anisotropic nature of the dipolar interactions. However, ΔAi values can be mapped semiquantitatively between the two cases if compared at common values of b2∗. Free energy landscapes of oligomerization are constructed, illustrating significant differences in landscape ruggedness for small clusters of dipolar versus SW fluids, and suggesting a possible molecular interpretation for empirical models of nucleation-dependent aggregation of proteins.

Error and efficiency of replica exchange molecular dynamics simulations

Rosta, Edina; Hummer, Gerhard
Fonte: U.S. Government Publicador: U.S. Government
Tipo: Artigo de Revista Científica
EN
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911.51305%
We derive simple analytical expressions for the error and computational efficiency of replica exchange molecular dynamics (REMD) simulations (and by analogy replica exchange Monte Carlo simulations). The theory applies to the important case of systems whose dynamics at long times is dominated by the slow interconversion between two metastable states. As a specific example, we consider the folding and unfolding of a protein. The efficiency is defined as the rate with which the error in an estimated equilibrium property, as measured by the variance of the estimator over repeated simulations, decreases with simulation time. For two-state systems, this rate is in general independent of the particular property. Our main result is that, with comparable computational resources used, the relative efficiency of REMD and molecular dynamics (MD) simulations is given by the ratio of the number of transitions between the two states averaged over all replicas at the different temperatures, and the number of transitions at the single temperature of the MD run. This formula applies if replica exchange is frequent, as compared to the transition times. High efficiency of REMD is thus achieved by including replica temperatures in which the frequency of transitions is higher than that at the temperature of interest. In tests of the expressions for the error in the estimator...

Positive feedback regulation results in spatial clustering and fast spreading of active signaling molecules on a cell membrane

Das, Jayajit; Kardar, Mehran; Chakraborty, Arup K.
Fonte: American Institute of Physics Publicador: American Institute of Physics
Tipo: Artigo de Revista Científica
EN
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Positive feedback regulation is ubiquitous in cell signaling networks, often leading to binary outcomes in response to graded stimuli. However, the role of such feedbacks in clustering, and in spatial spreading of activated molecules, has come to be appreciated only recently. We focus on the latter, using a simple model developed in the context of Ras activation with competing negative and positive feedback mechanisms. We find that positive feedback, in the presence of slow diffusion, results in clustering of activated molecules on the plasma membrane, and rapid spatial spreading as the front of the cluster propagates with a constant velocity (dependent on the feedback strength). The advancing fronts of the clusters of the activated species are rough, with scaling consistent with the Kardar–Parisi–Zhang equation in one dimension. Our minimal model is general enough to describe signal transduction in a wide variety of biological networks where activity in the membrane-proximal region is subject to feedback regulation.

Only signaling modules that discriminate sharply between stimulatory and nonstimulatory inputs require basal signaling for fast cellular responses

Artomov, Mykyta; Kardar, Mehran; Chakraborty, Arup K.
Fonte: American Institute of Physics Publicador: American Institute of Physics
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
910.5063%
In many types of cells, binding of molecules to their receptors enables cascades of intracellular chemical reactions to take place (signaling). However, a low level of signaling also occurs in most unstimulated cells. Such basal signaling in resting cells can have many functions, one of which is that it is thought to be required for fast cellular responses to external stimuli. A mechanistic understanding of why this is true and which features of cellular signaling networks make basal signaling necessary for fast responses is unknown. We address this issue by obtaining the time required for activation of common types of cell signaling modules with and without basal signaling. Our results show that the absence of basal signaling does not have any dramatic effects on the response time for signaling modules that exhibit a graded response to increasing stimulus levels. In sharp contrast, signaling modules that exhibit sharp dose-response curves which discriminate sensitively between stimuli to which the cell needs to respond and low-grade inputs (or stochastic noise) require basal signaling for fast cellular responses. In such cases, we find that an optimal level of basal signaling balances the requirements for fast cellular responses while minimizing spurious activation without appropriate stimulation.

Sequence composition and environment effects on residue fluctuations in protein structures

Ruvinsky, Anatoly M.; Vakser, Ilya A.
Fonte: American Institute of Physics Publicador: American Institute of Physics
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
903.58164%
Structure fluctuations in proteins affect a broad range of cell phenomena, including stability of proteins and their fragments, allosteric transitions, and energy transfer. This study presents a statistical-thermodynamic analysis of relationship between the sequence composition and the distribution of residue fluctuations in protein-protein complexes. A one-node-per-residue elastic network model accounting for the nonhomogeneous protein mass distribution and the interatomic interactions through the renormalized inter-residue potential is developed. Two factors, a protein mass distribution and a residue environment, were found to determine the scale of residue fluctuations. Surface residues undergo larger fluctuations than core residues in agreement with experimental observations. Ranking residues over the normalized scale of fluctuations yields a distinct classification of amino acids into three groups: (i) highly fluctuating-Gly, Ala, Ser, Pro, and Asp, (ii) moderately fluctuating-Thr, Asn, Gln, Lys, Glu, Arg, Val, and Cys, and (iii) weakly fluctuating-Ile, Leu, Met, Phe, Tyr, Trp, and His. The structural instability in proteins possibly relates to the high content of the highly fluctuating residues and a deficiency of the weakly fluctuating residues in irregular secondary structure elements (loops)...

Theory and simulation on the kinetics of protein–ligand binding coupled to conformational change

Cai, Lu; Zhou, Huan-Xiang
Fonte: American Institute of Physics Publicador: American Institute of Physics
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
903.4834%
Conformational change during protein–ligand binding may significantly affect both the binding mechanism and the rate constant. Most earlier theories and simulations treated conformational change as stochastic gating with transition rates between reactive and nonreactive conformations uncoupled to ligand binding. Recently, we introduced a dual-transition-rates model in which the transition rates between reactive and nonreactive conformations depend on the protein–ligand distance [H.-X. Zhou, Biophys. J. 98, L15 (2010)]. Analytical results of that model showed that the apparent binding mechanism switches from conformational selection to induced fit, when the rates of conformational transitions increase from being much slower than the diffusional approach of the protein–ligand pair to being much faster. The conformational-selection limit (kCS) and the induced-fit limit (kIF) provide lower and upper bounds, respectively, for the binding rate constant. Here we introduce a general model in which the energy surface of the protein in conformational space is coupled to ligand binding, and present a method for calculating the binding rate constant from Brownian dynamics simulations. Analytical and simulation results show that, for an energy surface that switches from favoring the nonreactive conformation while the ligand is away to favoring the reactive conformation while the ligand is near...

A permeation theory for single-file ion channels: One- and two-step models

Nelson, Peter Hugo
Fonte: American Institute of Physics Publicador: American Institute of Physics
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
903.4102%
How many steps are required to model permeation through ion channels? This question is investigated by comparing one- and two-step models of permeation with experiment and MD simulation for the first time. In recent MD simulations, the observed permeation mechanism was identified as resembling a Hodgkin and Keynes knock-on mechanism with one voltage-dependent rate-determining step [Jensen , PNAS 107, 5833 (2010)]. These previously published simulation data are fitted to a one-step knock-on model that successfully explains the highly non-Ohmic current–voltage curve observed in the simulation. However, these predictions (and the simulations upon which they are based) are not representative of real channel behavior, which is typically Ohmic at low voltages. A two-step association/dissociation (A/D) model is then compared with experiment for the first time. This two-parameter model is shown to be remarkably consistent with previously published permeation experiments through the MaxiK potassium channel over a wide range of concentrations and positive voltages. The A/D model also provides a first-order explanation of permeation through the Shaker potassium channel, but it does not explain the asymmetry observed experimentally. To address this...

Correlating anomalous diffusion with lipid bilayer membrane structure using single molecule tracking and atomic force microscopy

Skaug, Michael J.; Faller, Roland; Longo, Marjorie L.
Fonte: American Institute of Physics Publicador: American Institute of Physics
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
913.9148%
Anomalous diffusion has been observed abundantly in the plasma membrane of biological cells, but the underlying mechanisms are still unclear. In general, it has not been possible to directly image the obstacles to diffusion in membranes, which are thought to be skeleton bound proteins, protein aggregates, and lipid domains, so the dynamics of diffusing particles is used to deduce the obstacle characteristics. We present a supported lipid bilayer system in which we characterized the anomalous diffusion of lipid molecules using single molecule tracking, while at the same time imaging the obstacles to diffusion with atomic force microscopy. To explain our experimental results, we performed lattice Monte Carlo simulations of tracer diffusion in the presence of the experimentally determined obstacle configurations. We correlate the observed anomalous diffusion with obstacle area fraction, fractal dimension, and correlation length. To accurately measure an anomalous diffusion exponent, we derived an expression to account for the time-averaging inherent to all single molecule tracking experiments. We show that the length of the single molecule trajectories is critical to the determination of the anomalous diffusion exponent. We further discuss our results in the context of confinement models and the generating stochastic process.

Reexamining protein–protein and protein–solvent interactions from Kirkwood-Buff analysis of light scattering in multi-component solutions

Blanco, Marco A.; Sahin, Erinc; Li, Yi; Roberts, Christopher J.
Fonte: American Institute of Physics Publicador: American Institute of Physics
Tipo: Artigo de Revista Científica
EN
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903.4102%
The classic analysis of Rayleigh light scattering (LS) is re-examined for multi-component protein solutions, within the context of Kirkwood-Buff (KB) theory as well as a more generalized canonical treatment. Significant differences arise when traditional treatments that approximate constant pressure and neglect concentration fluctuations in one or more (co)solvent∕co-solute species are compared with more rigorous treatments at constant volume and with all species free to fluctuate. For dilute solutions, it is shown that LS can be used to rigorously and unambiguously obtain values for the osmotic second virial coefficient (B22), in contrast with recent arguments regarding protein interactions deduced from LS experiments. For more concentrated solutions, it is shown that conventional analysis over(under)-estimates the magnitude of B22 for significantly repulsive(attractive) conditions, and that protein-protein KB integrals (G22) are the more relevant quantity obtainable from LS. Published data for α–chymotrypsinogen A and a series of monoclonal antibodies at different pH and salt concentrations are re-analyzed using traditional and new treatments. The results illustrate that while traditional analysis may be sufficient if one is interested in only the sign of B22 or G22...

Exploration of the relationship between topology and designability of conformations

Leelananda, Sumudu P.; Towfic, Fadi; Jernigan, Robert L.; Kloczkowski, Andrzej
Fonte: American Institute of Physics Publicador: American Institute of Physics
Tipo: Artigo de Revista Científica
EN
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903.4102%
Protein structures are evolutionarily more conserved than sequences, and sequences with very low sequence identity frequently share the same fold. This leads to the concept of protein designability. Some folds are more designable and lots of sequences can assume that fold. Elucidating the relationship between protein sequence and the three-dimensional (3D) structure that the sequence folds into is an important problem in computational structural biology. Lattice models have been utilized in numerous studies to model protein folds and predict the designability of certain folds. In this study, all possible compact conformations within a set of two-dimensional and 3D lattice spaces are explored. Complementary interaction graphs are then generated for each conformation and are described using a set of graph features. The full HP sequence space for each lattice model is generated and contact energies are calculated by threading each sequence onto all the possible conformations. Unique conformation giving minimum energy is identified for each sequence and the number of sequences folding to each conformation (designability) is obtained. Machine learning algorithms are used to predict the designability of each conformation. We find that the highly designable structures can be distinguished from other non-designable conformations based on certain graphical geometric features of the interactions. This finding confirms the fact that the topology of a conformation is an important determinant of the extent of its designability and suggests that the interactions themselves are important for determining the designability.

Vibrational spectroscopy of water in hydrated lipid multi-bilayers. I. Infrared spectra and ultrafast pump-probe observables

Gruenbaum, S. M.; Skinner, J. L.
Fonte: American Institute of Physics Publicador: American Institute of Physics
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
914.9901%
The vibrational spectroscopy of hydration water in dilauroylphosphatidylcholine lipid multi-bilayers is investigated using molecular dynamics simulations and a mixed quantum∕classical model for the OD stretch spectroscopy of dilute HDO in H2O. FTIR absorption spectra, and isotropic and anisotropic pump-probe decay curves have been measured experimentally as a function of the hydration level of the lipid multi-bilayer, and our goal is to make connection with these experiments. To this end, we use third-order response functions, which allow us to include non-Gaussian frequency fluctuations, non-Condon effects, molecular rotations, and a fluctuating vibrational lifetime, all of which we believe are important for this system. We calculate the response functions using existing transition frequency and dipole maps. From the experiments it appears that there are two distinct vibrational lifetimes corresponding to HDO molecules in different molecular environments. In order to obtain these lifetimes, we consider a simple two-population model for hydration water hydrogen bonds. Assuming a different lifetime for each population, we then calculate the isotropic pump-probe decay, fitting to experiment to obtain the two lifetimes for each hydration level. With these lifetimes in hand...

Gay-Berne and electrostatic multipole based coarse-grain potential in implicit solvent

Wu, Johnny; Zhen, Xia; Shen, Hujun; Li, Guohui; Ren, Pengyu
Fonte: American Institute of Physics Publicador: American Institute of Physics
Tipo: Artigo de Revista Científica
EN
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A general, transferable coarse-grain (CG) framework based on the Gay-Berne potential and electrostatic point multipole expansion is presented for polypeptide simulations. The solvent effect is described by the Generalized Kirkwood theory. The CG model is calibrated using the results of all-atom simulations of model compounds in solution. Instead of matching the overall effective forces produced by atomic models, the fundamental intermolecular forces such as electrostatic, repulsion-dispersion, and solvation are represented explicitly at a CG level. We demonstrate that the CG alanine dipeptide model is able to reproduce quantitatively the conformational energy of all-atom force fields in both gas and solution phases, including the electrostatic and solvation components. Replica exchange molecular dynamics and microsecond dynamic simulations of polyalanine of 5 and 12 residues reveal that the CG polyalanines fold into “alpha helix” and “beta sheet” structures. The 5-residue polyalanine displays a substantial increase in the “beta strand” fraction relative to the 12-residue polyalanine. The detailed conformational distribution is compared with those reported from recent all-atom simulations and experiments. The results suggest that the new coarse-graining approach presented in this study has the potential to offer both accuracy and efficiency for biomolecular modeling.

On the inverse temperature transition and development of an entropic elastomeric force of the elastin mimetic peptide [LGGVG]3, 7

Huang, Jiaxin; Sun, Cheng; Mitchell, Odingo; Ng, Nicole; Wang, Zhao Na; Boutis, Gregory S.
Fonte: American Institute of Physics Publicador: American Institute of Physics
Tipo: Artigo de Revista Científica
EN
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We report on a molecular dynamics simulation based study of the thermal and mechanical properties of the elastin mimetic peptide [LGGVG]n (n = 3, 7). Our findings indicate that this peptide undergoes an inverse temperature transition as the temperature is raised from ∼20 °C to 42 °C. The thermal behavior is similar to what has been observed in other well studied short mimetic peptides of elastin. Both [LGGVG]n (n = 3, 7) peptides exhibit an increase in the number of side chain contacts and peptide-peptide hydrogen bonds when the temperature is raised from ∼20 °C to 42 °C. These observations are accompanied by a decrease in the number of proximal water molecules and number of peptide-water hydrogen bonds. This work also reports on a comparison of the thermal and mechanical properties of [LGGVG]3 and [VPGVG]3 and quantifies the interaction with surrounding waters of hydration under mechanically strained conditions. It is demonstrated, via a quasi-harmonic approach, that both model peptides exhibit a reduction in the population of low-frequency modes and an increase in population of high-frequency modes upon elongation. The shift in population of frequency modes causes the peptide entropy to decrease upon elongation and is responsible for the development of an entropic force that gives rise to elasticity. These observations are in disagreement with a previously published notion that model elastin peptides...