Constructing Optimal Coarse-Grained Sites of Huge Biomolecules by Fluctuation Maximization

Min Li, John Zenghui Zhang, Fei Xia

Research output: Contribution to journalArticle

Abstract

Coarse-grained (CG) models are valuable tools for the study of functions of large biomolecules on large length and time scales. The definition of CG representations for huge biomolecules is always a formidable challenge. In this work, we propose a new method called fluctuation maximization coarse-graining (FM-CG) to construct the CG sites of biomolecules. The defined residual in FM-CG converges to a maximal value as the number of CG sites increases, allowing an optimal CG model to be rigorously defined on the basis of the maximum. More importantly, we developed a robust algorithm called stepwise local iterative optimization (SLIO) to accelerate the process of coarse-graining large biomolecules. By means of the efficient SLIO algorithm, the computational cost of coarse-graining large biomolecules is reduced to within the time scale of seconds, which is far lower than that of conventional simulated annealing. The coarse-graining of two huge systems, chaperonin GroEL and lengsin, indicates that our new methods can coarse-grain huge biomolecular systems with up to 10 000 residues within the time scale of minutes. The further parametrization of CG sites derived from FM-CG allows us to construct the corresponding CG models for studies of the functions of huge biomolecular systems.

Original languageEnglish (US)
Pages (from-to)2091-2100
Number of pages10
JournalJournal of chemical theory and computation
Volume12
Issue number4
DOIs
StatePublished - Apr 12 2016

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ASJC Scopus subject areas

  • Computer Science Applications
  • Physical and Theoretical Chemistry

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