Folding Trp-cage to NMR resolution native structure using a coarse-grained protein model

Feng Ding, Sergey V. Buldyrev, Nikolay Dokholyan

Research output: Contribution to journalArticle

111 Citations (Scopus)

Abstract

We develop a coarse-grained protein model with a simplified amino acid interaction potential. Using this model, we perform discrete molecular dynamics folding simulations of a small 20-residue protein-Trp-cage-from a fully extended conformation. We demonstrate the ability of the Trp-cage model to consistently reach conformations within 2-Å backbone root-mean-square distance from the corresponding NMR structures. The minimum root-mean-square distance of Trp-cage conformations in simulations can be < 1 Å. Our findings suggest that, at least in the case of Trp-cage, a detailed all-atom protein model with a molecular mechanics force field is not necessary to reach the native state of a protein. Our results also suggest that the success of folding Trp-cage in our simulations and in the reported all-atom molecular mechanics simulation studies may be mainly due to the special stabilizing features specific to this miniprotein.

Original languageEnglish (US)
Pages (from-to)147-155
Number of pages9
JournalBiophysical journal
Volume88
Issue number1
DOIs
StatePublished - Jan 1 2005

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Mechanics
Proteins
Molecular Dynamics Simulation
Amino Acids

All Science Journal Classification (ASJC) codes

  • Biophysics

Cite this

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abstract = "We develop a coarse-grained protein model with a simplified amino acid interaction potential. Using this model, we perform discrete molecular dynamics folding simulations of a small 20-residue protein-Trp-cage-from a fully extended conformation. We demonstrate the ability of the Trp-cage model to consistently reach conformations within 2-{\AA} backbone root-mean-square distance from the corresponding NMR structures. The minimum root-mean-square distance of Trp-cage conformations in simulations can be < 1 {\AA}. Our findings suggest that, at least in the case of Trp-cage, a detailed all-atom protein model with a molecular mechanics force field is not necessary to reach the native state of a protein. Our results also suggest that the success of folding Trp-cage in our simulations and in the reported all-atom molecular mechanics simulation studies may be mainly due to the special stabilizing features specific to this miniprotein.",
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Folding Trp-cage to NMR resolution native structure using a coarse-grained protein model. / Ding, Feng; Buldyrev, Sergey V.; Dokholyan, Nikolay.

In: Biophysical journal, Vol. 88, No. 1, 01.01.2005, p. 147-155.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Folding Trp-cage to NMR resolution native structure using a coarse-grained protein model

AU - Ding, Feng

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AU - Dokholyan, Nikolay

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AB - We develop a coarse-grained protein model with a simplified amino acid interaction potential. Using this model, we perform discrete molecular dynamics folding simulations of a small 20-residue protein-Trp-cage-from a fully extended conformation. We demonstrate the ability of the Trp-cage model to consistently reach conformations within 2-Å backbone root-mean-square distance from the corresponding NMR structures. The minimum root-mean-square distance of Trp-cage conformations in simulations can be < 1 Å. Our findings suggest that, at least in the case of Trp-cage, a detailed all-atom protein model with a molecular mechanics force field is not necessary to reach the native state of a protein. Our results also suggest that the success of folding Trp-cage in our simulations and in the reported all-atom molecular mechanics simulation studies may be mainly due to the special stabilizing features specific to this miniprotein.

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