GAMESS As a Free Quantum-Mechanical Platform for Drug Research

Alexeev, Yuri; Mazanetz, Michael P.; Ichihara, Osamu; Fedorov, Dmitri G.

doi:10.2174/156802612804910269

Cited by 118 publications

(73 citation statements)

References 197 publications

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“…85 Then, the FMO-DFT analytic Hessian was implemented in GAMESS and was parallelized using the generalized distributed data interface (GDDI). 61,86,87 For all calculations, the 6-31G(d) basis set with spherical harmonics was used.…”

Section: Computational Detailsmentioning

confidence: 99%

Analytic second derivative of the energy for density functional theory based on the three-body fragment molecular orbital method

Nakata

Fedorov

Zahariev

et al. 2015

The Journal of Chemical Physics

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Analytic second derivatives of the energy with respect to nuclear coordinates have been developed for spin restricted density functional theory (DFT) based on the fragment molecular orbital method (FMO). The derivations were carried out for the three-body expansion (FMO3), and the two-body expressions can be obtained by neglecting the three-body corrections. Also, the restricted Hartree-Fock (RHF) Hessian for FMO3 can be obtained by neglecting the density-functional related terms. In both the FMO-RHF and FMO-DFT Hessians, certain terms with small magnitudes are neglected for computational efficiency. The accuracy of the FMO-DFT Hessian in terms of the Gibbs free energy is evaluated for a set of polypeptides and water clusters and found to be within 1 kcal/mol of the corresponding full (non-fragmented) ab initio calculation. The FMO-DFT method is also applied to transition states in SN2 reactions and for the computation of the IR and Raman spectra of a small Trp-cage protein (PDB: 1L2Y). Some computational timing analysis is also presented. KeywordsProteins, Polymers, Free energy, Raman spectra, Biochemical reactions Disciplines Chemistry CommentsThe following article appeared in Journal of Chemical Physics 142 (2015) Analytic second derivatives of the energy with respect to nuclear coordinates have been developed for spin restricted density functional theory (DFT) based on the fragment molecular orbital method (FMO). The derivations were carried out for the three-body expansion (FMO3), and the two-body expressions can be obtained by neglecting the three-body corrections. Also, the restricted HartreeFock (RHF) Hessian for FMO3 can be obtained by neglecting the density-functional related terms. In both the FMO-RHF and FMO-DFT Hessians, certain terms with small magnitudes are neglected for computational efficiency. The accuracy of the FMO-DFT Hessian in terms of the Gibbs free energy is evaluated for a set of polypeptides and water clusters and found to be within 1 kcal/mol of the corresponding full (non-fragmented) ab initio calculation. The FMO-DFT method is also applied to transition states in S N 2 reactions and for the computation of the IR and Raman spectra of a small Trp-cage protein (PDB: 1L2Y). Some computational timing analysis is also presented. C 2015 AIP Publishing LLC.[http://dx

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Section: Computational Detailsmentioning

confidence: 99%

Analytic second derivative of the energy for density functional theory based on the three-body fragment molecular orbital method

Nakata

Fedorov

Zahariev

et al. 2015

The Journal of Chemical Physics

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“…Charges for all three ligands were calculated with GAMESS program (Alexeev et al, 2012) using Mulliken charges and Hartree-Fock method in 6-31G* basis with the pre-optimizing (with DFT method with B3LYP functional) molecule geometry. Protonation states were predicted at pH 5,3 as the protein.…”

Section: Ligand Preparationmentioning

confidence: 99%

Docking and Molecular Dynamics (MD) Simulations in Potential Drugs Discovery: An Application to Influenza Virus M2 Protein

Bozdaganyan¹,

Orekhov²,

Bragazzi³

et al. 2014

American Journal of Biochemistry and Biotechnology

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Molecular docking is a common method for searching new potential drugs. Improvement of the results of docking can be achieved by different ways-one of them is molecular dynamics simulations of protein-ligand complexes. As a model for our research we chose M2 membrane protein from influenza virus. M2 protein is a high selective tetrameric pH-gated proton channel. It was previously shown that Omeprazole Family Compounds (OFC) block the "proton pump", though we hypothesized further that they could interfere with the mechanism of fusion of the virus envelope and endosomal membrane, thereby hindering the M2 proton pump mechanism of influenza viruses. We carried out a Molecular Dynamics (MD) simulation in order to predict constant of binding for OFC. We simulated M2 Protein (PDB code 3C9J) in complex with its ligands: Amantadine, rimantadine as positive controls and omeprazole as putative ligand. We made use of molecular docking as well as the thermodynamic integration method to estimate binding free energies of the ligands. We demonstrate that the thermodynamic integration method predicts free energies of ligand binding better than molecular docking while embedding of M2 protein in a membrane further improves the calculated free energy values. Free energy calculations imply omeprazole as a potent anti-viral drug.

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“…The IR spectra and high-performance liquid chromatography (HPLC) of purine nucleoside analogs and residues of thermal decomposition at different stages were measured. The molecular bond orders of purine nucleoside analogs were calculated with ab initio methods of quantum chemistry (GAMESS package) [27][28][29]. Thermal decomposition mechanisms of purine nucleoside analogs were discussed.…”

Section: Introductionmentioning

confidence: 99%

Study on the molecular structure and thermal stability of purine nucleoside analogs

Wang

You

2015

Journal of Analytical and Applied Pyrolysis

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GAMESS As a Free Quantum-Mechanical Platform for Drug Research

Cited by 118 publications

References 197 publications

Analytic second derivative of the energy for density functional theory based on the three-body fragment molecular orbital method

Analytic second derivative of the energy for density functional theory based on the three-body fragment molecular orbital method

Docking and Molecular Dynamics (MD) Simulations in Potential Drugs Discovery: An Application to Influenza Virus M2 Protein

Study on the molecular structure and thermal stability of purine nucleoside analogs

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