Protocol

Molecular Modeling of Proteins

Volume 1215 of the series Methods in Molecular Biology pp 445-469

Date:

Molecular Docking to Flexible Targets

  • Jesper SørensenAffiliated withDepartment of Chemistry and Biochemistry, University of California
  • , Özlem DemirAffiliated withDepartment of Chemistry and Biochemistry, University of California
  • , Robert V. SwiftAffiliated withDepartment of Chemistry and Biochemistry, University of California
  • , Victoria A. FeherAffiliated withDepartment of Chemistry and Biochemistry, University of California
  • , Rommie E. AmaroAffiliated withDepartment of Chemistry and Biochemistry, University of California Email author 

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Abstract

It is widely accepted that protein receptors exist as an ensemble of conformations in solution. How best to incorporate receptor flexibility into virtual screening protocols used for drug discovery remains a significant challenge. Here, stepwise methodologies are described to generate and select relevant protein conformations for virtual screening in the context of the relaxed complex scheme (RCS), to design small molecule libraries for docking, and to perform statistical analyses on the virtual screening results. Methods include equidistant spacing, RMSD-based clustering, and QR factorization protocols for ensemble generation and ROC analysis for ensemble selection.

Key words

Relaxed complex scheme Ligand filtering Protein flexibility QR factorization RMSD-based clustering ROC analysis