MM2QM tool can be downloaded from http://theultimatechemistry.com/software.html.
The MM2QM tool for combining docking, molecular dynamics, molecular mechanics, and quantum mechanics†
Article first published online: 12 DEC 2012
Copyright © 2012 Wiley Periodicals, Inc.
Journal of Computational Chemistry
Volume 34, Issue 9, pages 750–756, 5 April 2013
How to Cite
Nowosielski, M., Hoffmann, M., Kuron, A., Korycka-Machala, M. and Dziadek, J. (2013), The MM2QM tool for combining docking, molecular dynamics, molecular mechanics, and quantum mechanics. J. Comput. Chem., 34: 750–756. doi: 10.1002/jcc.23192
- Issue published online: 26 FEB 2013
- Article first published online: 12 DEC 2012
- Manuscript Accepted: 6 NOV 2012
- Manuscript Revised: 2 NOV 2012
- Manuscript Received: 21 MAR 2012
- InterMolMed project. Grant Number: POIG.01.01.02-10-107/09
- PL-Grid project. Grant Number: POIG.02.03.00-00-007/08-00
- European Regional Development Fund as part of the Innovative Economy Program
- drug design;
- molecular mechanics;
- quantum mechanics
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 Å. Protein–ligand 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. © 2012 Wiley Periodicals, Inc.