title: Multiple copy sampling: rigid versus flexible protein.
abstract: Effects of protein flexibility on multiple copy conformational sampling were systematically evaluated by studying the side-chain placement of Phe-14 in protein Zif268. The multiple copy sampling is shown to be significantly more efficient when a flexible but harmonically constrained protein is used instead of a rigid protein. A range of constraint force from 1 to 25 kcal/mol.A per atom is determined to be sufficient to prevent the protein from distortion while allowing the protein to fluctuate for enhanced sampling. The protein fluctuations are essential in smoothing the effective energy surface as shown by the opening-closing of a protein hydrophobic pocket during a multiple copy energy minimization, a phenomenon that has been previously observed only in molecular dynamics. These results provide a practical guidance for applying the multiple copy techniques to molecular modeling and computer-aided drug design.
authors.affiliation: Scios Nova Inc., Baltimore, Maryland 21224.
authors.forename: Q
authors.initials: Q
authors.lastname: Zheng
authors.forename: D J
authors.initials: DJ
authors.lastname: Kyle
mesh_terms: D007611:Aprotinin / Q000737:chemistry; D003198:Computer Simulation; D004268:DNA-Binding Proteins / Q000737:chemistry*; D015195:Drug Design; D007610:Kallikreins / Q000737:chemistry; D008958:Models, Molecular; D011487:Protein Conformation; D014157:Transcription Factors / Q000737:chemistry*; D016335:Zinc Fingers
chemical_list: D004268:DNA-Binding Proteins; D014157:Transcription Factors; D007611:Aprotinin; D007610:Kallikreins