Applications of the Fragment Molecular Orbital Method to Drug Research

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


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.


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) 



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.



Assisted Model Building with Energy Refinement


Computer-Aided Drug Design


Chemistry at HARvard Macromolecular Mechanics


Effective Fragment Potential


Electrostatic Potential


Frozen Domain


Frozen Domain and Dimers


Fragment Molecular Orbital


General Atomic and Molecular Electronic Structure System


Large-scale Atomic/Molecular Massively Parallel Simulator


Molecular Dynamics


Molecular Mechanics




Polarizable Continuum Model


Pair Interaction Energy


PIE Decomposition Analysis


Quantum Mechanical


Quantitative SAR


Structure-Activity Relationship


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
    Email author
  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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