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Multiple copy sampling: Rigid versus flexible protein
Author(s) -
Zheng Qiang,
Kyle Donald J.
Publication year - 1994
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.340190407
Subject(s) - sampling (signal processing) , smoothing , flexibility (engineering) , molecular dynamics , constraint (computer aided design) , umbrella sampling , biological system , computer science , algorithm , chemistry , computational chemistry , mathematics , biology , geometry , statistics , filter (signal processing) , computer vision
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. Å 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. © 1994 Wiley‐Liss, Inc.