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Understanding folding and design: replica-exchange simulations of "Trp-cage" miniproteins.

ABSTRACT: Replica-exchange molecular dynamics simulations in implicit solvent have been carried out to study the folding thermodynamics of a designed 20-residue peptide, or "miniprotein." The simulations in this study used the amber (parm94) force field along with the generalized Born/solvent-accessible surface area implicit solvent model, and they spanned a range of temperatures from 273 to 630 K. Starting from a completely extended initial conformation, simulations of one peptide sequence sample conformations that are <1.0 A Calpha rms positional deviation from structures in the corresponding NMR ensemble. These folded states are thermodynamically stable with a simulated melting temperature of approximately 400 K, and they satisfy the majority of experimentally observed NMR restraints. Simulations of a related mutant peptide show a degenerate ensemble of states at low temperature, in agreement with experimental results.

SUBMITTER: Pitera JW

PROVIDER: S-EPMC164630 | biostudies-literature | 2003 Jun

REPOSITORIES: biostudies-literature

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Understanding folding and design: replica-exchange simulations of "Trp-cage" miniproteins.

Pitera Jed W JW Swope William W

Proceedings of the National Academy of Sciences of the United States of America 20030613 13

Replica-exchange molecular dynamics simulations in implicit solvent have been carried out to study the folding thermodynamics of a designed 20-residue peptide, or "miniprotein." The simulations in this study used the amber (parm94) force field along with the generalized Born/solvent-accessible surface area implicit solvent model, and they spanned a range of temperatures from 273 to 630 K. Starting from a completely extended initial conformation, simulations of one peptide sequence sample conform ...[more]

PMID: 12808142

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