Simulating protein motions with rigidity analysis

Shawna Thomas, Xinyu Tang, Lydia Tapia, Nancy M. Amato

Research output: Contribution to journalArticlepeer-review

Abstract

Protein motions, ranging from molecular flexibility to large-scale conformational change, play an essential role in many biochemical processes. Despite the explosion in our knowledge of structural and functional data, our understanding of protein movement is still very limited. In previous work, we developed and validated a motion planning based method for mapping protein folding pathways from unstructured conformations to the native state. In this paper, we propose a novel method based on rigidity theory to sample conformation space more effectively, and we describe extensions of our framework to automate the process and to map transitions between specified conformations. Our results show that these additions both improve the accuracy of our maps and enable us to study a broader range of motions for larger proteins. For example, we show that rigidity-based sampling results in maps that capture subtle folding differences between protein G and its mutants, NuG1 and NuG2, and we illustrate how our technique can be used to study large-scale conformational changes in calmodulin, a 148 residue signaling protein known to undergo conformational changes when binding to Ca2+. Finally, we announce our web-based protein folding server which includes a publicly available archive of protein motions: http://parasol.tamu.edu/foldingserver/.

Original languageEnglish (US)
Pages (from-to)839-855
Number of pages17
JournalJournal of Computational Biology
Volume14
Issue number6
DOIs
StatePublished - Jul 1 2007
Externally publishedYes

Keywords

  • Motion planning
  • Protein folding
  • Rigidity analysis

ASJC Scopus subject areas

  • Modeling and Simulation
  • Molecular Biology
  • Genetics
  • Computational Mathematics
  • Computational Theory and Mathematics

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