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Applications of the Fragment Molecular Orbital Method to Drug Research

  • Michael P. Mazanetz
  • Ewa Chudyk
  • Dmitri G. Fedorov
  • Yuri Alexeev
Protocol
Part of the Methods in Pharmacology and Toxicology book series (MIPT)

Abstract

The study of molecular behavior at high levels of theoretical accuracy has entered into a new age in computational drug discovery where quantum mechanical (QM) methods are becoming increasingly popular. Theoretically rigorous calculations can be prohibitively computationally expensive and time consuming. These two factors have necessitated the development of faster methods, and the fragment molecular orbital method (FMO) is one such method that has been used for efficient and accurate QM calculations in drug design. In this chapter, the use of FMO is described in detail for predicting geometry, estimating the binding energy of the ligands, conformational sampling, analysis of molecular interactions, deriving partial charges, and generating quantitative structure-activity relationship (QSAR) models.

Keywords

QM (quantum mechanics) Quantum chemistry FMO (fragment molecular orbitals method) CADD (computer-aided drug design) SBDD (structure-based drug design) GAMESS (general atomic and molecular electronic structure system) PIEDA (pair interaction energy decomposition analysis) 

Notes

Acknowledgments

Dmitri G. Fedorov has been supported by the Next Generation Super Computing Project, Nanoscience Program (MEXT, Japan) and Computational Materials Science Initiative (CMSI, Japan). This research used resources of the Argonne Leadership Computing Facility, which is a DOE Office of Science User Facility supported under Contract DE-AC02-06CH11357.

The submitted manuscript has been created by UChicago Argonne, LLC, Operator of Argonne National Laboratory (“Argonne”). Argonne, a US Department of Energy Office of Science laboratory, is operated under Contract No. DE-AC02-06CH11357. The US Government retains for itself, and others acting on its behalf, a paid-up nonexclusive, irrevocable worldwide license in said article to reproduce, prepare derivative works, distribute copies to the public, and perform publicly and display publicly, by or on behalf of the government.

Glossary

AMBER

Assisted Model Building with Energy Refinement

CADD

Computer-Aided Drug Design

CHARMM

Chemistry at HARvard Macromolecular Mechanics

EFP

Effective Fragment Potential

ESP

Electrostatic Potential

FD

Frozen Domain

FDD

Frozen Domain and Dimers

FMO

Fragment Molecular Orbital

GAMESS

General Atomic and Molecular Electronic Structure System

LAMMPS

Large-scale Atomic/Molecular Massively Parallel Simulator

MD

Molecular Dynamics

MM

Molecular Mechanics

PB

Poisson–Boltzmann

PCM

Polarizable Continuum Model

PIE

Pair Interaction Energy

PIEDA

PIE Decomposition Analysis

QM

Quantum Mechanical

QSAR

Quantitative SAR

SAR

Structure-Activity Relationship

SBDD

Structure Based Drug Design

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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Michael P. Mazanetz
    • 1
  • Ewa Chudyk
    • 1
  • Dmitri G. Fedorov
    • 2
  • Yuri Alexeev
    • 3
  1. 1.Evotec (UK) LtdAbingdonUK
  2. 2.Nanomaterials Research InstituteNational Institute of Advanced Industrial Science and Technology (AIST)TsukubaJapan
  3. 3.Leadership Computing FacilityArgonne National LaboratoryArgonneUSA

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