期刊
JOURNAL OF COMPUTATIONAL CHEMISTRY
卷 34, 期 31, 页码 2726-2741出版社
WILEY
DOI: 10.1002/jcc.23448
关键词
absolute free energy; conformational state; random energy model; computational protein design
资金
- NIH [5F32GM084631-02]
- NSF [CNS-1205521]
- Dartmouth College
Computing the absolute free energy of a macromolecule's structural state, F, is a challenging problem of high relevance. This study presents a method that computes F using only information from an unperturbed simulation of the macromolecule in the relevant conformational state, ensemble, and environment. Absolute free energies produced by this method, dubbed Valuation of Local Configuration Integral with Dynamics (VALOCIDY), enable comparison of alternative states. For example, comparing explicitly solvated and vaporous states of amino acid sidechain analogs produces solvation free energies in good agreement with experiments. Also, comparisons between alternative conformational states of model heptapeptides (including the unfolded state) produce free energy differences in agreement with data from mu s molecular-dynamics simulations and experimental propensities. The potential of using VALOCIDY in computational protein design is explored via a small design problem of stabilizing a beta-turn structure. When VALOCIDY-based estimation of folding free energy is used as the design metric, the resulting sequence folds into the desired structure within the atomistic force field used in design. The VALOCIDYbased approach also recognizes the distinct status of the native sequence regardless of minor details of the starting template structure, in stark contrast with a traditional fixed-backbone approach. (C) 2013 Wiley Periodicals, Inc.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据