Dataset Information

Free-energy landscape of the GB1 hairpin in all-atom explicit solvent simulations with different force fields: Similarities and differences.

ABSTRACT: Although it is now possible to fold peptides and miniproteins in molecular dynamics simulations, it is well appreciated that force fields are not all transferable to different proteins. Here, we investigate the influence of the protein force field and the solvent model on the folding energy landscape of a prototypical two-state folder, the GB1 hairpin. We use extensive replica-exchange molecular dynamics simulations to characterize the free-energy surface as a function of temperature. Most of these force fields appear similar at a global level, giving a fraction folded at 300 K between 0.2 and 0.8 in all cases, which is a difference in stability of 2.8 kT, and are generally consistent with experimental data at this temperature. The most significant differences appear in the unfolded state, where there are different residual secondary structures which are populated, and the overall dimensions of the unfolded states, which in most of the force fields are too collapsed relative to experimental Förster Resonance Energy Transfer (FRET) data.

SUBMITTER: Best RB

PROVIDER: S-EPMC4228318 | biostudies-literature | 2011 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Free-energy landscape of the GB1 hairpin in all-atom explicit solvent simulations with different force fields: Similarities and differences.

Best Robert B RB Mittal Jeetain J

Proteins 20110214 4

Although it is now possible to fold peptides and miniproteins in molecular dynamics simulations, it is well appreciated that force fields are not all transferable to different proteins. Here, we investigate the influence of the protein force field and the solvent model on the folding energy landscape of a prototypical two-state folder, the GB1 hairpin. We use extensive replica-exchange molecular dynamics simulations to characterize the free-energy surface as a function of temperature. Most of th ...[more]

PMID: 21322056

Similar Datasets

Project description:We describe the derivation of a set of bonded and nonbonded coarse-grained (CG) potential functions for use in implicit-solvent Brownian dynamics (BD) simulations of proteins derived from all-atom explicit-solvent molecular dynamics (MD) simulations of amino acids. Bonded potential functions were derived from 1 μs MD simulations of each of the 20 canonical amino acids, with histidine modeled in both its protonated and neutral forms; nonbonded potential functions were derived from 1 μs MD simulations of every possible pairing of the amino acids (231 different systems). The angle and dihedral probability distributions and radial distribution functions sampled during MD were used to optimize a set of CG potential functions through use of the iterative Boltzmann inversion (IBI) method. The optimized set of potential functions-which we term COFFDROP (COarse-grained Force Field for Dynamic Representation Of Proteins)-quantitatively reproduced all of the "target" MD distributions. In a first test of the force field, it was used to predict the clustering behavior of concentrated amino acid solutions; the predictions were directly compared with the results of corresponding all-atom explicit-solvent MD simulations and found to be in excellent agreement. In a second test, BD simulations of the small protein villin headpiece were carried out at concentrations that have recently been studied in all-atom explicit-solvent MD simulations by Petrov and Zagrovic (PLoS Comput. Biol.2014, 5, e1003638). The anomalously strong intermolecular interactions seen in the MD study were reproduced in the COFFDROP simulations; a simple scaling of COFFDROP's nonbonded parameters, however, produced results in better accordance with experiment. Overall, our results suggest that potential functions derived from simulations of pairwise amino acid interactions might be of quite broad applicability, with COFFDROP likely to be especially useful for modeling unfolded or intrinsically disordered proteins.

Dataset Information

Free-energy landscape of the GB1 hairpin in all-atom explicit solvent simulations with different force fields: Similarities and differences.

Publications

Free-energy landscape of the GB1 hairpin in all-atom explicit solvent simulations with different force fields: Similarities and differences.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets