Dataset Information

Analysis of molecular dynamics simulations of 10-residue peptide, chignolin, using statistical mechanics: Relaxation mode analysis and three-dimensional reference interaction site model theory.

ABSTRACT: Molecular dynamics simulation is a fruitful tool for investigating the structural stability, dynamics, and functions of biopolymers at an atomic level. In recent years, simulations can be performed on time scales of the order of milliseconds using special purpose systems. Since the most stable structure, as well as meta-stable structures and intermediate structures, is included in trajectories in long simulations, it is necessary to develop analysis methods for extracting them from trajectories of simulations. For these structures, methods for evaluating the stabilities, including the solvent effect, are also needed. We have developed relaxation mode analysis to investigate dynamics and kinetics of simulations based on statistical mechanics. We have also applied the three-dimensional reference interaction site model theory to investigate stabilities with solvent effects. In this paper, we review the results for designing amino-acid substitution of the 10-residue peptide, chignolin, to stabilize the misfolded structure using these developed analysis methods.

SUBMITTER: Maruyama Y

PROVIDER: S-EPMC6975981 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Analysis of molecular dynamics simulations of 10-residue peptide, chignolin, using statistical mechanics: Relaxation mode analysis and three-dimensional reference interaction site model theory.

Maruyama Yutaka Y Takano Hiroshi H Mitsutake Ayori A

Biophysics and physicobiology 20191129

Molecular dynamics simulation is a fruitful tool for investigating the structural stability, dynamics, and functions of biopolymers at an atomic level. In recent years, simulations can be performed on time scales of the order of milliseconds using special purpose systems. Since the most stable structure, as well as meta-stable structures and intermediate structures, is included in trajectories in long simulations, it is necessary to develop analysis methods for extracting them from trajectories ...[more]

PMID: 31984194

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Project description:BackgroundAnalysis of known protein structures reveals that identical sequence fragments in proteins can adopt different secondary structure conformations. The extent of this conformational diversity is influenced by various factors like the intrinsic sequence propensity, sequence context and other environmental factors such as pH, site directed mutations or alteration of the binding ligands. Understanding the mechanism by which the environment affects the structural ambivalence of these peptides has potential implications for protein design and reliable local structure prediction algorithms. Identification of the structurally ambivalent sequence fragments and determining the rules which dictate their conformational preferences play an important role in understanding the conformational changes observed in misfolding diseases. However, a systematic classification of their intrinsic sequence patterns or a statistical analysis of their properties and sequence context in relation to the origin of their structural diversity have largely remained unexplored.ResultsIn this work, the conformational variability of α-helices is studied by mapping sequences from the non-redundant database to identical sequences across all classes of the SCOP (Structural Classification of Proteins) database. Some helices retain their conformations when mapped in the SCOP database while others exhibit a complete/partial switch to non-helical conformations. The results clearly depict the differences in the propensities of amino acids for the variable and conserved helices. Sequences flanking these ambivalent sequence fragments have anisotropic propensities at the N- and C-termini. This structural variability is depicted by molecular dynamics simulations in explicit solvent, which show that the short conserved helices retain their conformations while their longer counterparts fray into two or more shorter helices. Variable helices in the non-redundant database exhibit a trend of retaining helical conformations while their corresponding non-helical conformations in SCOP database show large deviations from their respective initial structures by adopting partial or full helical conformations. Partially ambivalent helices are also found to retain their respective conformations.ConclusionsAll sequence fragments which show structural diversity in different proteins of the non-redundant database are investigated. The final conformation of these ambivalent sequences are dictated by a fine tuning of their intrinsic sequence propensity and the anisotropic amino acid propensity of the flanking sequences. This analysis may unravel the connection between diverse secondary structures, which conserve the overall structural fold of the protein thus determining its function.

Dataset Information

Analysis of molecular dynamics simulations of 10-residue peptide, chignolin, using statistical mechanics: Relaxation mode analysis and three-dimensional reference interaction site model theory.

Publications

Analysis of molecular dynamics simulations of 10-residue peptide, chignolin, using statistical mechanics: Relaxation mode analysis and three-dimensional reference interaction site model theory.

Similar Datasets

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