Nowosielski, Marcin; Hoffmann, Marcin; Kuron, Aneta; Korycka-Machala, Malgorzata; Dziadek, Jaroslaw
The MM2QM tool for combining docking, molecular dynamics, molecular mechanics, and quantum mechanics dagger
JOURNAL OF COMPUTATIONAL CHEMISTRY, 34:750-756, APR 5 2013

The use of the MM2QM tool in a combined docking + molecular dynamics (MD) + molecular mechanics (MM) + quantum mechanical (QM) binding affinity prediction study is presented, and the tool itself is discussed. The system of interest is Mycobacterium tuberculosis (MTB) pantothenate synthetase in complexes with three highly similar sulfonamide inhibitors, for which crystal structures are available. Starting from the structure of MTB pantothenate synthetase in the open conformation and following the combined docking + MD + MM + QM procedure, we were able to capture the closing of the enzyme binding pocket and to reproduce the position of the ligands with an average root mean square deviation of 1.6 angstrom. Proteinligand interaction energies were reproduced with an average error lower than 10%. The discussion on the MD part and a protein flexibility importance is carried out. The presented approach may be useful especially for finding analog inhibitors or improving drug candidates. (c) 2012 Wiley Periodicals, Inc.

DOI:10.1002/jcc.23192

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