Interdisciplinary Bio Central
 
Review (Bioinformatics/Computational biology/Molecular modeling)

Fragment Molecular Orbital Method: Application to Protein-Ligand Binding
Hirofumi Watanabe1,2,* and Shigenori Tanaka2,3,*
1Graduate School of Engineering, Kobe University, 1-1, Rokkodai, Nada, Kobe 657-8501, Japan
2JST-CREST
3Graduate School of System Informatics, Department of Computational Science, Kobe University, 1-1, Rokkodai, Nada, Kobe 657-8501, Japan
*Corresponding author
  Received : May 31, 2010
  Accepted : June 07, 2010
  Published : June 10, 2010
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
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Synopsis

Fragment molecular orbital (FMO) method provides a novel tool for ab initio calculations of large biomolecules. This method overcomes the size limitation difficulties in conventional molecular orbital methods and has several advantages compared to classical force field approaches. While there are many features in this method, we here focus on explaining the issues related to protein-ligand binding: FMO method provides useful interaction-analysis tools such as IFIE, CAFI and FILM. FMO calculations can provide not only binding energies, which are well correlated with experimental binding affinity, but also QSAR descriptors. In addition, FMO-derived charges improve the descriptions of electrostatic properties and the correlations between docking scores and experimental binding affinities. These calculations can be performed by the ABINIT-MPX program and the calculation results can be visualized by its proper BioStation Viewer. The acceleration of FMO calculations on various computer facilities is ongoing, and we are also developing methods to deal with cytochrome P450, which belongs to the family of drug metabolic enzymes.

Keyword: fragment molecular orbital method, protein-ligand binding affinity, QSAR
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