690 research outputs found
Effect of the solvent on the conformational behavior of the alanine dipeptide deduced from MD simulations
In general, peptides do not exhibit a well-defined conformational profile in solution. However, despite the experimental blurred picture associated with their structure, compelling spectroscopic evidence shows that peptides exhibit local order. The conformational profile of a peptide is the result of a balance between intramolecular interactions between different atoms of the molecule and intermolecular interactions between atoms of the molecule and the solvent. Accordingly, the conformational profile of a peptide will change upon the properties of the solvent it is soaked. To get insight into the balance between intra- and intermolecular interactions on the conformational preferences of the peptide backbone we have studied the conformational profile of the alanine dipeptide in diverse solvents using molecular dynamics as sampling technique. Solvents studied include chloroform, methanol, dimethyl sulfoxide, water and N-methylacetamide. Different treatments of the solvent have been studied in the present work including explicit solvent molecules, a generalized Born model and using the bulk dielectric constant of the solvent. The diverse calculations identify four major conformations with different populations in the diverse solvents: the C7 eq only sampled in chloroform; the C5 or extended conformation; the polyproline (PII) conformation and the right-handed a-helix conformation (aR). The results of present calculations permit to analyze how the balance between intra- and intermolecular interactions explains the populations of the diverse conformations observed.Postprint (published version
Exploring the conformational dynamics of alanine dipeptide in solution subjected to an external electric field: A nonequilibrium molecular dynamics simulation
In this paper, we investigate the conformational dynamics of alanine
dipeptide under an external electric field by nonequilibrium molecular dynamics
simulation. We consider the case of a constant and of an oscillatory field. In
this context we propose a procedure to implement the temperature control, which
removes the irrelevant thermal effects of the field. For the constant field
different time-scales are identified in the conformational, dipole moment, and
orientational dynamics. Moreover, we prove that the solvent structure only
marginally changes when the external field is switched on. In the case of
oscillatory field, the conformational changes are shown to be as strong as in
the previous case, and non-trivial nonequilibrium circular paths in the
conformation space are revealed by calculating the integrated net probability
fluxes.Comment: 23 pages, 12 figure
Effect of the solvent on the conformational behavior of the alanine dipeptide deduced from MD simulations
In general, peptides do not exhibit a well-defined conformational profile in solution. However, despite the experimental blurred picture associated with their structure, compelling spectroscopic evidence shows that peptides exhibit local order. The conformational profile of a peptide is the result of a balance between intramolecular interactions between different atoms of the molecule and intermolecular interactions between atoms of the molecule and the solvent. Accordingly, the conformational profile of a peptide will change upon the properties of the solvent it is soaked. To get insight into the balance between intraand intermolecular interactions on the conformational preferences of the peptide backbone we have studied the conformational profile of the alanine dipeptide in diverse solvents using molecular dynamics as sampling technique. Solvents studied include chloroform, methanol, dimethyl sulfoxide, water and N-methylacetami de. Different treatments of the solvent have been studied in the present work including explicit solvent molecules, a generalized Born model and using the bulk dielectric constant of the solvent. The diverse calculations identify four major conformations with different populations in the diverse solvents: the C-7(eq) only sampled in chloroform; the C-5 or extended conformation; the polyproline (PII) conformation and the right-handed alpha-helix conformation (alpha(R)). The results of present calculations permit to analyze how the balance between intra- and intermolecular interactions explains the populations of the diverse conformations observed. (C) 2017 Elsevier Inc. All rights reserved
Leap-dynamics: efficient sampling of conformational space of proteins and peptides in solution
AbstractA molecular simulation scheme, called Leap-dynamics, that provides efficient sampling of protein conformational space in solution is presented. The scheme is a combined approach using a fast sampling method, imposing conformational ‘leaps’ to force the system over energy barriers, and molecular dynamics (MD) for refinement. The presence of solvent is approximated by a potential of mean force depending on the solvent accessible surface area. The method has been successfully applied to N-acetyl-L-alanine-N-methylamide (alanine dipeptide), sampling experimentally observed conformations inaccessible to MD alone under the chosen conditions. The method predicts correctly the increased partial flexibility of the mutant Y35G compared to native bovine pancreatic trypsin inhibitor. In particular, the improvement over MD consists of the detection of conformational flexibility that corresponds closely to slow motions identified by nuclear magnetic resonance techniques
Glutathione as a Prebiotic Answer to alpha-Peptide Based Life.
The energetics of peptide bond formation is an important factor not only in the design of chemical peptide synthesis, but it also has a role in protein biosynthesis. In this work, quantum chemical calculations at 10 different levels of theory including G3MP2B3 were performed on the energetics of glutathione formation. The strength of the peptide bond is found to be closely related to the acid strength of the to-be N-terminal and the basicity of the to-be C-terminal amino acid. It is shown that the formation of the first peptide activates the amino acid for the next condensation step, manifested in bacterial protein synthesis where the first step is the formation of an N-formylmethionine dipeptide. The possible role of glutathione in prebiotic molecular evolution is also analyzed. The implications of the thermodynamics of peptide bond formation in prebiotic peptide formation as well as in the preference of alpha- instead of beta- or gamma-amino acids are discussed. An empirical correction is proposed for the compensation of the error due to the incapability of continuum solvation models in describing the change of the first solvation shell when a peptide bond is formed from two zwitterions accompanied by the disappearance of one ion pair
Adaptive Resolution Simulation in Equilibrium and Beyond
In this paper, we investigate the equilibrium statistical properties of both
the force and potential interpolations of adaptive resolution simulation
(AdResS) under the theoretical framework of grand-canonical like AdResS
(GC-AdResS). The thermodynamic relations between the higher and lower
resolutions are derived by considering the absence of fundamental conservation
laws in mechanics for both branches of AdResS. In order to investigate the
applicability of AdResS method in studying the properties beyond the
equilibrium, we demonstrate the accuracy of AdResS in computing the dynamical
properties in two numerical examples: The velocity auto-correlation of pure
water and the conformational relaxation of alanine dipeptide dissolved in
water. Theoretical and technical open questions of the AdResS method are
discussed in the end of the paper
Doctor of Philosophy
dissertationAdvances in computer hardware have enabled routine MD simulations of systems with tens of thousands of atoms for up to microseconds (soon milliseconds). The key limiting factor in whether these simulations can advance hypothesis testing in active research is the accuracy of the force fields. In many ways, force fields for RNA are less mature than those for proteins. Yet even the current generation of force fields offers benefits to researchers as we demonstrate with our re-refinement effort on two RNA hairpins. Additionally, our simulation study of the binding of 2-aminobenzimidazole inhibitors to hepatitis C RNA offers a computational perspective on which of the two rather different published structures (one NMR, the other X-ray) is a more reasonable structure for future CADD efforts as well as which free energy methods are suited to these highly charged complexes. Finally, further effort on force field improvement is critical. We demonstrate an effective method to determine quantitative conformational population analysis of small RNAs using enhanced sampling methods. These efforts are allowing us to uncover force field pathologies and quickly test new modifications. In summary, this research serves to strengthen communication between experimental and theoretical methods in order produce mutual benefit
Introduction to protein folding for physicists
The prediction of the three-dimensional native structure of proteins from the
knowledge of their amino acid sequence, known as the protein folding problem,
is one of the most important yet unsolved issues of modern science. Since the
conformational behaviour of flexible molecules is nothing more than a complex
physical problem, increasingly more physicists are moving into the study of
protein systems, bringing with them powerful mathematical and computational
tools, as well as the sharp intuition and deep images inherent to the physics
discipline. This work attempts to facilitate the first steps of such a
transition. In order to achieve this goal, we provide an exhaustive account of
the reasons underlying the protein folding problem enormous relevance and
summarize the present-day status of the methods aimed to solving it. We also
provide an introduction to the particular structure of these biological
heteropolymers, and we physically define the problem stating the assumptions
behind this (commonly implicit) definition. Finally, we review the 'special
flavor' of statistical mechanics that is typically used to study the
astronomically large phase spaces of macromolecules. Throughout the whole work,
much material that is found scattered in the literature has been put together
here to improve comprehension and to serve as a handy reference.Comment: 53 pages, 18 figures, the figures are at a low resolution due to
arXiv restrictions, for high-res figures, go to http://www.pabloechenique.co
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