Generating stereochemically acceptable protein pathways

Daniel W. Farrell, Kirill Speranskiy, Michael Thorpe

Research output: Contribution to journalArticle

60 Scopus citations

Abstract

We describe a new method for rapidly generating stereochemically acceptable pathways in proteins. The method, called geometric targeting, is publicly available at the webserver http://pathways.asu.edu, and includes tools for visualization of the pathway and creating movie files for use in presentations. The user submits an initial structure and a target structure, and a pathway between the two input states is generated automatically. Besides visualization, the structural quality of the pathways makes them useful as input pathways into pathway refinement techniques and further computations. The approach in geometric targeting is to gradually change the system's RMSD relative to the target structure while enforcing a set of geometric constraints. The generated pathways are not minimum free energy pathways, but they are geometrically plausible pathways that maintain good covalent bond distances and angles, keep backbone dihedral angles in allowed Ramachandran regions, avoid eclipsed side-chain torsion angles, avoid nonbonded overlap, and maintain a set of hydrogen bonds and hydrophobic contacts. Resulting pathways for over 20 proteins featuring a wide variety of conformational changes are reported here, including the very large GroEL complex.

Original languageEnglish (US)
Pages (from-to)2908-2921
Number of pages14
JournalProteins: Structure, Function and Bioinformatics
Volume78
Issue number14
DOIs
StatePublished - Nov 1 2010

Keywords

  • Conformational change
  • Conformational sampling
  • Geometric simulation
  • Geometric targeting
  • Movies
  • Target
  • Transition

ASJC Scopus subject areas

  • Structural Biology
  • Biochemistry
  • Molecular Biology

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