Understanding folding and design: Replica-exchange simulations of ``Trp-cage'' miniproteins

Proceedings of the National Academy of Sciences of the United States of America - Tập 100 Số 13 - Trang 7587-7592 - 2003
Jed W. Pitera1, William C. Swope2,3
1IBM Research, Almaden Research Center, 650 Harry Road, San Jose CA, 95120, USA
2IBM Research, Almaden Research Center, 650 Harry Road, San Jose, CA 95120
3University of California at San Diego, La Jolla, CA

Tóm tắt

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 Å C α rms positional deviation from structures in the corresponding NMR ensemble. These folded states are thermodynamically stable with a simulated melting temperature of ≈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.

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

Tập 100 Số 13

7587-7592

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