1,738 research outputs found
Recurrence quantification analysis as a tool for the characterization of molecular dynamics simulations
A molecular dynamics simulation of a Lennard-Jones fluid, and a trajectory of
the B1 immunoglobulin G-binding domain of streptococcal protein G (B1-IgG)
simulated in water are analyzed by recurrence quantification, which is
noteworthy for its independence from stationarity constraints, as well as its
ability to detect transients, and both linear and nonlinear state changes. The
results demonstrate the sensitivity of the technique for the discrimination of
phase sensitive dynamics. Physical interpretation of the recurrence measures is
also discussed.Comment: 7 pages, 8 figures, revtex; revised for review for Phys. Rev. E
(clarifications and expansion of discussion)-- addition of the 8 postscript
figures previously omitted, but unchanged from version
Molecular dynamics simulation of polymer helix formation using rigid-link methods
Molecular dynamics simulations are used to study structure formation in
simple model polymer chains that are subject to excluded volume and torsional
interactions. The changing conformations exhibited by chains of different
lengths under gradual cooling are followed until each reaches a state from
which no further change is possible. The interactions are chosen so that the
true ground state is a helix, and a high proportion of simulation runs succeed
in reaching this state; the fraction that manage to form defect-free helices is
a function of both chain length and cooling rate. In order to demonstrate
behavior analogous to the formation of protein tertiary structure, additional
attractive interactions are introduced into the model, leading to the
appearance of aligned, antiparallel helix pairs. The simulations employ a
computational approach that deals directly with the internal coordinates in a
recursive manner; this representation is able to maintain constant bond lengths
and angles without the necessity of treating them as an algebraic constraint
problem supplementary to the equations of motion.Comment: 15 pages, 14 figure
Maximum Flux Transition Paths of Conformational Change
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
different from that of the MaxFlux method of Huo and Straub.) 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.Comment: 7 figure
Integrity of H1 helix in prion protein revealed by molecular dynamic simulations to be especially vulnerable to changes in the relative orientation of H1 and its S1 flank
In the template-assistance model, normal prion protein (PrPC), the pathogenic
cause of prion diseases such as Creutzfeldt-Jakob (CJD) in human, Bovine
Spongiform Encephalopathy (BSE) in cow, and scrapie in sheep, converts to
infectious prion (PrPSc) through an autocatalytic process triggered by a
transient interaction between PrPC and PrPSc. Conventional studies suggest the
S1-H1-S2 region in PrPC to be the template of S1-S2 -sheet in PrPSc, and
the conformational conversion of PrPC into PrPSc may involve an unfolding of H1
in PrPC and its refolding into the -sheet in PrPSc. Here we conduct a
series of simulation experiments to test the idea of transient interaction of
the template-assistance model. We find that the integrity of H1 in PrPC is
vulnerable to a transient interaction that alters the native dihedral angles at
residue Asn, which connects the S1 flank to H1, but not to interactions
that alter the internal structure of the S1 flank, nor to those that alter the
relative orientation between H1 and the S2 flank.Comment: A major revision on statistical analysis method has been made. The
paper now has 23 pages, 11 figures. This work was presented at 2006 APS March
meeting session K29.0004 at Baltimore, MD, USA 3/13-17, 2006. This paper has
been accepted for pubcliation in European Biophysical Journal on Feb 2, 200
Isomorphs in model molecular liquids
Isomorphs are curves in the phase diagram along which a number of static and
dynamic quantities are invariant in reduced units. A liquid has good isomorphs
if and only if it is strongly correlating, i.e., the equilibrium
virial/potential energy fluctuations are more than 90% correlated in the NVT
ensemble. This paper generalizes isomorphs to liquids composed of rigid
molecules and study the isomorphs of two systems of small rigid molecules, the
asymmetric dumbbell model and the Lewis-Wahnstrom OTP model. In particular, for
both systems we find that the isochoric heat capacity, the excess entropy, the
reduced molecular center-of-mass self part of the intermediate scattering
function, the reduced molecular center-of-mass radial distribution function to
a good approximation are invariant along an isomorph. In agreement with theory,
we also find that an instantaneous change of temperature and density from an
equilibrated state point to another isomorphic state point leads to no
relaxation. The isomorphs of the Lewis-Wahnstrom OTP model were found to be
more approximative than those of the asymmetric dumbbell model, which is
consistent with the OTP model being less strongly correlating. For both models
we find "master isomorphs", i.e., isomorphs have identical shape in the
virial/potential energy phase diagram.Comment: 20 page
Growth of (110) Diamond using pure Dicarbon
We use a density-functional based tight-binding method to study diamond
growth steps by depositing dicarbon species onto a hydrogen-free diamond (110)
surface. Subsequent C_2 molecules are deposited on an initially clean surface,
in the vicinity of a growing adsorbate cluster, and finally, near vacancies
just before completion of a full new monolayer. The preferred growth stages
arise from C_2n clusters in near ideal lattice positions forming zigzag chains
running along the [-110] direction parallel to the surface. The adsorption
energies are consistently exothermic by 8--10 eV per C_2, depending on the size
of the cluster. The deposition barriers for these processes are in the range of
0.0--0.6 eV. For deposition sites above C_2n clusters the adsorption energies
are smaller by 3 eV, but diffusion to more stable positions is feasible. We
also perform simulations of the diffusion of C_2 molecules on the surface in
the vicinity of existing adsorbate clusters using an augmented Lagrangian
penalty method. We find migration barriers in excess of 3 eV on the clean
surface, and 0.6--1.0 eV on top of graphene-like adsorbates. The barrier
heights and pathways indicate that the growth from gaseous dicarbons proceeds
either by direct adsorption onto clean sites or after migration on top of the
existing C_2n chains.Comment: 8 Pages, 7 figure
Coarse-Graining Protein Structures With Local Multivariate Features from Molecular Dynamics
A multivariate statistical theory, local feature analysis (LFA), extracts functionally relevant domains from molecular dynamics (MD) trajectories. The LFA representations, like those of principal component analysis (PCA), are low dimensional and provide a reduced basis set for collective motions of simulated proteins, but the local features are sparsely distributed and spatially localized, in contrast to global PCA modes. One key problem in the assignment of local features is the coarse-graining of redundant LFA output functions by means of seed atoms. One can solve the combinatorial problem by adding seed atoms one after another to a growing set, minimizing a reconstruction error at each addition. This allows for an efficient implementation, but the sequential algorithm does not guarantee the optimal mutual correlation of the sequentially assigned features. Here, we present a novel coarse-graining algorithm for proteins that directly minimizes the mutual correlation of seed atoms by Monte Carlo (MC) simulations. Tests on MD trajectories of two biological systems, bacteriophage T4 lysozyme and myosin II motor domain S1, demonstrate that the new algorithm provides statistically reproducible results and describes functionally relevant dynamics. The well-known undersampling of large-scale motion by short MD simulations is apparent also in our model, but the new coarse-graining offers a major advantage over PCA; converged features are invariant across multiple windows of the trajectory, dividing the protein into converged regions and a smaller number of localized, undersampled regions. In addition to its use in structure classification, the proposed coarse-graining thus provides a localized measure of MD sampling efficiency
A critical assessment of methods for the intrinsic analysis of liquid interfaces. 1. surface site distributions
Substantial progress in our understanding of interfacial structure and dynamics has stemmed from the recent development of algorithms that allow for an intrinsic analysis of fluid interfaces. These work by identifying the instantaneous location of the interface, at the atomic level, for each molecular configuration and then computing properties relative to this location. Such a procedure eliminates the broadening of the interface caused by capillary waves and reveals the underlying features of the system. However, a precise definition of which molecules actually belong to the interfacial layer is difficult to achieve in practice. Furthermore, it is not known if the different intrinsic analysis methods are consistent with each other and yield similar results for the interfacial properties. In this paper, we carry out a systematic and detailed comparison of the available methods for intrinsic analysis of fluid interfaces, based on a molecular dynamics simulation of the interface between liquid water and carbon tetrachloride. We critically assess the advantages and shortcomings of each method, based on reliability, robustness, and speed of computation, and establish consistent criteria for determining which molecules belong to the surface layer. We believe this will significantly contribute to make intrinsic analysis methods widely and routinely applicable to interfacial systems
Protecting High Energy Barriers: A New Equation to Regulate Boost Energy in Accelerated Molecular Dynamics Simulations
Molecular dynamics (MD) is one of the most common tools in computational chemistry. Recently, our group has employed accelerated molecular dynamics (aMD) to improve the conformational sampling over conventional molecular dynamics techniques. In the original aMD implementation, sampling is greatly improved by raising energy wells below a predefined energy level. Recently, our group presented an alternative aMD implementation where simulations are accelerated by lowering energy barriers of the potential energy surface. When coupled with thermodynamic integration simulations, this implementation showed very promising results. However, when applied to large systems, such as proteins, the simulation tends to be biased to high energy regions of the potential landscape. The reason for this behavior lies in the boost equation used since the highest energy barriers are dramatically more affected than the lower ones. To address this issue, in this work, we present a new boost equation that prevents oversampling of unfavorable high energy conformational states. The new boost potential provides not only better recovery of statistics throughout the simulation but also enhanced sampling of statistically relevant regions in explicit solvent MD simulations
Differential Base Stacking Interactions Induced by Trimethylene Interstrand DNA Cross-Links in the 5′-CpG-3′ and 5′-GpC-3′ Sequence Contexts
Synthetically derived trimethylene interstrand DNA cross-links have been used as surrogates for the native cross-links that arise from the 1,N 2-deoxyguanosine adducts derived from R,β-unsaturated aldehydes. The native enal-mediated cross-linking occurs in the 5′-CpG-3 ′ sequence context but not in the 5′-GpC-3 ′ sequence context. The ability of the native enal-derived 1,N 2-dG adducts to induce interstrand DNA cross-links in the 5′-CpG-3 ′ sequence as opposed to the 5′-GpC-3 ′ sequence is attributed to the destabilization of the DNA duplex in the latter sequence context. Here, we report higher accuracy solution structures of the synthetically derived trimethylene cross-links, which are refined from NMR data with the AMBER force field. When the synthetic trimethylene cross-links are placed into either the 5′-CpG-3′ or the 5′-GpC-3 ′ sequence contexts, the DNA duplex maintains B-DNA geometry with structural perturbations confined to the cross-linked base pairs. Watson-Crick hydrogen bonding is conserved throughout the duplexes. Although different from canonical B-DNA stacking, the cross-linked and the neighbor base pairs stack in the 5′-CpG-3 ′ sequence. In contrast, the stacking at the cross-linked base pairs in the 5′-GpC-3 ′ sequence is greatly perturbed. The π-stacking interactions between the crosslinked and the neighbor base pairs are reduced. This is consistent with remarkable chemical shift perturbations of the C 5 H5 and H6 nucleobase protons that shifted downfield by 0.4-0.5 ppm. In contrast
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