Applications of the Fragment Molecular Orbital Method to Drug Research

The energy and analytic gradient are developed for FMO combined with the Hartree-Fock method augmented with three empirical corrections (HF-3c). The auxiliary basis set approach to FMO is extended to perform pair interaction energy decomposition analysis. The FMO accuracy is evaluated for several typical systems including 3 proteins. Pair interaction energies computed with different approaches in FMO are compared for a water cluster and protein-ligand complexes.

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“…For drug discovery applications [46], the correlation is important. The PIEs for MP2 and HF-3c are shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

Empirical corrections and pair interaction energies in the fragment molecular orbital method

Fedorov

Kromann

Jensen

2018

Chemical Physics Letters

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“…179,180 The ligand binding analysis was compared to experiment. 170,176,181 Molecular electrostatic potential can be evaluated with FMO, 66,176 which is useful to gain insight into binding.…”

Section: Overview Of Applicationsmentioning

confidence: 99%

“…Biochemical applications of FMO focus on protein–ligand complexes, nucleic acids, saccharides, and enzymatic catalysis . Pair interactions provide useful information about the recognition of ligands by proteins, which can be used in drug discovery . The validity of FMO to order native and decoy structures, as related to protein folding, was examined .…”

Section: Overview Of Applicationsmentioning

confidence: 99%

“…The validity of FMO to order native and decoy structures, as related to protein folding, was examined . The ligand binding analysis was compared to experiment . Molecular electrostatic potential can be evaluated with FMO, which is useful to gain insight into binding.…”

Section: Overview Of Applicationsmentioning

confidence: 99%

“…[173][174][175] Pair interactions provide useful information about the recognition of ligands by proteins, which can be used in drug discovery. [176][177][178] The validity of FMO to order native and decoy structures, as related to protein folding, was examined. 179,180 The ligand binding analysis was compared to experiment.…”

Section: Overview Of Applicationsmentioning

confidence: 99%

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The fragment molecular orbital method: theoretical development, implementation in GAMESS, and applications

Fedorov

2017

WIREs Comput Mol Sci

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130

122

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The physical picture of the fragment molecular orbital (FMO) method is described on the basis of a many‐body expansion with terms describing the polarization of isolated fragments, charge transfer (CT), and exchange‐repulsion (EX) between them. Aspects of fragmentation are discussed in detail and FMO development in GAMESS‐US is summarized. Recent progress in method development and applications is reviewed, with a focus on studies of protein–ligand binding, excited states, and spectra of large molecular systems. WIREs Comput Mol Sci 2017, 7:e1322. doi: 10.1002/wcms.1322 This article is categorized under: Structure and Mechanism > Computational Biochemistry and Biophysics Electronic Structure Theory > Ab Initio Electronic Structure Methods

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Efficient Geometry Optimization of Large Molecular Systems in Solution Using the Fragment Molecular Orbital Method

Nakata

Fedorov

2016

J. Phys. Chem. A

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The analytic gradient is derived for the frozen domain formulation of the fragment molecular orbital (FMO) method combined with the polarizable continuum model. The accuracy is tested in comparison to full FMO calculations for a representative set of systems in terms of the gradient accuracy, protein-ligand binding energies, and optimized structures. The frozen domain method reproduced geometries optimized with full FMO within 0.03-0.09 Å in terms of reduced mean square deviations, whereas a single-point gradient calculation is accelerated by the factor of 38 (Trp-cage protein in explicit solvent, PDB: 1L2Y ) and 12 (crambin, PDB: 1CRN ). The method is applied to a geometry optimization of the K-Ras protein-ligand complex (4Q03) using two domain definitions, and the optimized structures are consistent with experiment. Pair interaction analysis is used to identify residues important in binding the ligand.

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Applications of the Fragment Molecular Orbital Method to Drug Research

Cited by 6 publications

References 143 publications

Empirical corrections and pair interaction energies in the fragment molecular orbital method

Empirical corrections and pair interaction energies in the fragment molecular orbital method

The fragment molecular orbital method: theoretical development, implementation in GAMESS, and applications

Efficient Geometry Optimization of Large Molecular Systems in Solution Using the Fragment Molecular Orbital Method

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