85 research outputs found
Coarse Graining of Nonbonded Inter-particle Potentials Using Automatic Simplex Optimization to Fit Structural Properties
We implemented a coarse-graining procedure to construct mesoscopic models of
complex molecules. The final aim is to obtain better results on properties
depending on slow modes of the molecules. Therefore the number of particles
considered in molecular dynamics simulations is reduced while conserving as
many properties of the original substance as possible. We address the problem
of finding nonbonded interaction parameters which reproduce structural
properties from experiment or atomistic simulations. The approach consists of
optimizing automatically nonbonded parameters using the simplex algorithm to
fit structural properties like the radial distribution function as target
functions. Moreover, any mix of structural and thermodynamic properties can be
included in the target function. Different spherically symmetric inter-particle
potentials are discussed. Besides demonstrating the method for Lennard--Jones
liquids, it is applied to several more complex molecular liquids such as
diphenyl carbonate, tetrahydrofurane, and monomers of poly(isoprene).Comment: 24 pages, 3 tables, 14 figures submitted to the Journal of Chemical
Physics (JCP
Evidence for size-dependent mechanical properties from simulations of nanoscopic polymeric structures
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Thermal Degradation of Adsorbed Bottle-Brush Macromolecules: Molecular Dynamics Simulation
The scission kinetics of bottle-brush molecules in solution and on an
adhesive substrate is modeled by means of Molecular Dynamics simulation with
Langevin thermostat. Our macromolecules comprise a long flexible polymer
backbone with segments, consisting of breakable bonds, along with two side
chains of length , tethered to each segment of the backbone. In agreement
with recent experiments and theoretical predictions, we find that bond cleavage
is significantly enhanced on a strongly attractive substrate even though the
chemical nature of the bonds remains thereby unchanged.
We find that the mean bond life time decreases upon adsorption by
more than an order of magnitude even for brush molecules with comparatively
short side chains $N=1 \div 4$. The distribution of scission probability along
the bonds of the backbone is found to be rather sensitive regarding the
interplay between length and grafting density of side chains. The life time
declines with growing contour length as ,
and with side chain length as . The probability
distribution of fragment lengths at different times agrees well with
experimental observations. The variation of the mean length of the
fragments with elapsed time confirms the notion of the thermal degradation
process as a first order reaction.Comment: 15 pages, 7 figure
RaKUn: Rank-based Keyword extraction via Unsupervised learning and Meta vertex aggregation
Keyword extraction is used for summarizing the content of a document and
supports efficient document retrieval, and is as such an indispensable part of
modern text-based systems. We explore how load centrality, a graph-theoretic
measure applied to graphs derived from a given text can be used to efficiently
identify and rank keywords. Introducing meta vertices (aggregates of existing
vertices) and systematic redundancy filters, the proposed method performs on
par with state-of-the-art for the keyword extraction task on 14 diverse
datasets. The proposed method is unsupervised, interpretable and can also be
used for document visualization.Comment: The final authenticated publication is available online at
https://doi.org/10.1007/978-3-030-31372-2_2
Nonlinearity of Mechanochemical Motions in Motor Proteins
The assumption of linear response of protein molecules to thermal noise or
structural perturbations, such as ligand binding or detachment, is broadly used
in the studies of protein dynamics. Conformational motions in proteins are
traditionally analyzed in terms of normal modes and experimental data on
thermal fluctuations in such macromolecules is also usually interpreted in
terms of the excitation of normal modes. We have chosen two important protein
motors - myosin V and kinesin KIF1A - and performed numerical investigations of
their conformational relaxation properties within the coarse-grained elastic
network approximation. We have found that the linearity assumption is deficient
for ligand-induced conformational motions and can even be violated for
characteristic thermal fluctuations. The deficiency is particularly pronounced
in KIF1A where the normal mode description fails completely in describing
functional mechanochemical motions. These results indicate that important
assumptions of the theory of protein dynamics may need to be reconsidered.
Neither a single normal mode, nor a superposition of such modes yield an
approximation of strongly nonlinear dynamics.Comment: 10 pages, 6 figure
Characterization of the Channel Constriction Allowing the Access of the Substrate to the Active Site of Yeast Oxidosqualene Cyclase
In oxidosqualene cyclases (OSCs), an enzyme which has been extensively studied as a target for hypocholesterolemic or antifungal drugs, a lipophilic channel connects the surface of the protein with the active site cavity. Active site and channel are separated by a narrow constriction operating as a mobile gate for the substrate passage. In Saccharomyces cerevisiae OSC, two aminoacidic residues of the channel/constriction apparatus, Ala525 and Glu526, were previously showed as critical for maintaining the enzyme functionality. In this work sixteen novel mutants, each bearing a substitution at or around the channel constrictions, were tested for their enzymatic activity. Modelling studies showed that the most functionality-lowering substitutions deeply alter the H-bond network involving the channel/constriction apparatus. A rotation of Tyr239 is proposed as part of the mechanism permitting the access of the substrate to the active site. The inhibition of OSC by squalene was used as a tool for understanding whether the residues under study are involved in a pre-catalytic selection and docking of the substrate oxidosqualene
Specialized dynamical properties of promiscuous residues revealed by simulated conformational ensembles
The ability to interact with different partners is one of the most important features in proteins. Proteins that bind a large number of partners (hubs) have been often associated with intrinsic disorder. However, many examples exist of hubs with an ordered structure, and evidence of a general mechanism promoting promiscuity in ordered proteins is still elusive. An intriguing hypothesis is that promiscuous binding sites have specific dynamical properties, distinct from the rest of the interface and pre-existing in the protein isolated state. Here, we present the first comprehensive study of the intrinsic dynamics of promiscuous residues in a large protein data set. Different computational methods, from coarse-grained elastic models to geometry-based sampling methods and to full-atom Molecular Dynamics simulations, were used to generate conformational ensembles for the isolated proteins. The flexibility and dynamic correlations of interface residues with a different degree of binding promiscuity were calculated and compared considering side chain and backbone motions, the latter both on a local and on a global scale. The study revealed that (a) promiscuous residues tend to be more flexible than nonpromiscuous ones, (b) this additional flexibility has a higher degree of organization, and (c) evolutionary conservation and binding promiscuity have opposite effects on intrinsic dynamics. Findings on simulated ensembles were also validated on ensembles of experimental structures extracted from the Protein Data Bank (PDB). Additionally, the low occurrence of single nucleotide polymorphisms observed for promiscuous residues indicated a tendency to preserve binding diversity at these positions. A case study on two ubiquitin-like proteins exemplifies how binding promiscuity in evolutionary related proteins can be modulated by the fine-tuning of the interface dynamics. The interplay between promiscuity and flexibility highlighted here can inspire new directions in protein-protein interaction prediction and design methods. © 2013 American Chemical Society
Functional clustering of yeast proteins from the protein-protein interaction network
BACKGROUND: The abundant data available for protein interaction networks have not yet been fully understood. New types of analyses are needed to reveal organizational principles of these networks to investigate the details of functional and regulatory clusters of proteins. RESULTS: In the present work, individual clusters identified by an eigenmode analysis of the connectivity matrix of the protein-protein interaction network in yeast are investigated for possible functional relationships among the members of the cluster. With our functional clustering we have successfully predicted several new protein-protein interactions that indeed have been reported recently. CONCLUSION: Eigenmode analysis of the entire connectivity matrix yields both a global and a detailed view of the network. We have shown that the eigenmode clustering not only is guided by the number of proteins with which each protein interacts, but also leads to functional clustering that can be applied to predict new protein interactions
Prediction of Mechanical Properties of Polymers With Various Force Fields
The effect of force field type on the predicted elastic properties of a polyimide is examined using a multiscale modeling technique. Molecular Dynamics simulations are used to predict the atomic structure and elastic properties of the polymer by subjecting a representative volume element of the material to bulk and shear finite deformations. The elastic properties of the polyimide are determined using three force fields: AMBER, OPLS-AA, and MM3. The predicted values of Young s modulus and shear modulus of the polyimide are compared with experimental values. The results indicate that the mechanical properties of the polyimide predicted with the OPLS-AA force field most closely matched those from experiment. The results also indicate that while the complexity of the force field does not have a significant effect on the accuracy of predicted properties, small differences in the force constants and the functional form of individual terms in the force fields determine the accuracy of the force field in predicting the elastic properties of the polyimide
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