Coarse-Graining Protein Energetics in Sequence Variables

Fei Zhou, Gevorg Grigoryan, Steve R. Lustig, Amy E. Keating, Gerbrand Ceder, and Dane Morgan
Phys. Rev. Lett. 95, 148103 – Published 29 September 2005

Abstract

We show that cluster expansions (CE), previously used to model solid-state materials with binary or ternary configurational disorder, can be extended to the protein design problem. We present a generalized CE framework, in which properties such as energy can be unambiguously expanded in the amino-acid sequence space. The CE coarse grains over nonsequence degrees of freedom (e.g., side-chain conformations) and thereby simplifies the problem of designing proteins, or predicting the compatibility of a sequence with a given structure, by many orders of magnitude. The CE is physically transparent, and can be evaluated through linear regression on the energies of training sequences. We show, as example, that good prediction accuracy is obtained with up to pairwise interactions for a coiled-coil backbone, and that triplet interactions are important in the energetics of a more globular zinc-finger backbone.

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  • Received 17 March 2005

DOI:https://doi.org/10.1103/PhysRevLett.95.148103

©2005 American Physical Society

Authors & Affiliations

Fei Zhou1, Gevorg Grigoryan2, Steve R. Lustig3, Amy E. Keating2, Gerbrand Ceder4, and Dane Morgan5

  • 1Department of Physics, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
  • 2Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
  • 3DuPont Central Research and Development, Experimental Station, Wilmington, Delaware 19880, USA
  • 4Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
  • 5Department of Materials Science and Engineering, University of Wisconsin, Madison, Wisconsin 53706, USA

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Issue

Vol. 95, Iss. 14 — 30 September 2005

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