Novel Quantitative Structure-Activity Studies of HIV-1 Protease Inhibitors of the Cyclic Urea Type Using Descriptors Derived from Molecular Dynamics and Molecular Orbital Calculations

Yoshida, Tatsusada; Fujita, Toshio; Chuman, Hiroshi

doi:10.2174/157340909787580845

Cited by 36 publications

(42 citation statements)

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“…To verify that the response contribution that has been derived and implemented in this study makes the FMO energy gradients fully analytic, analytic gradients are compared with numerical gradients for molecular systems taken from previous studies: 80,91,92 (H 2 O) 64 , the α-helix conformation of the alanine decamer (ALA) 10 capped with -OCH 3 and -NHCH 3 groups, chignolin (PDB ID: 1UAO) solvated by 157 water molecules, and the Trp-cage miniprotein construct (PDB ID: 1L2Y). The structures of (ALA) 10 taken from earlier works.…”

Section: Computational Detailsmentioning

confidence: 99%

“…The geometrical structure of (H 2 O) 64 was modeled by HYPERCHEM, optimized by AMBER94, 93 and then reoptimized at the FMO-RHF/6-31G level. 80 The optimized structure of (H 2 O) 64 is depicted in Fig. 2(a).…”

Section: Computational Detailsmentioning

confidence: 99%

“…34 For systems fragmented across covalent bonds, i.e., (ALA) 10 , chignolin and 1L2Y, a one residue/one fragment partition was adopted. The gradient calculations for (H 2 O) 64 , (ALA) 10 , hydrated chignolin, and 1L2Y were performed at the RHF/6-31G(d) level and diffuse functions were added to the carboxyl groups of 1L2Y. Additionally, RHF/6-311G(d) was also used to calculate the gradients for (H 2 O) 64 .…”

Section: Computational Detailsmentioning

confidence: 99%

“…The gradient calculations for (H 2 O) 64 , (ALA) 10 , hydrated chignolin, and 1L2Y were performed at the RHF/6-31G(d) level and diffuse functions were added to the carboxyl groups of 1L2Y. Additionally, RHF/6-311G(d) was also used to calculate the gradients for (H 2 O) 64 .…”

Section: Computational Detailsmentioning

confidence: 99%

“…The FMO method has been applied to a number of large systems. [53][54][55][56][57][58][59][60][61][62][63][64][65][66] FMO-MD has been used [67][68][69][70][71][72][73][74][75][76][77][78] to study the dynamics of various processes such as chemical reactions. However, the FMO-MD method suffers from an accumulation of errors 67 with the time evolution due to an incomplete analytic FMO energy gradient.…”

Section: Introductionmentioning

confidence: 99%

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Fully analytic energy gradient in the fragment molecular orbital method

Brorsen¹,

Fedorov²

2011

The Journal of Chemical Physics

100

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The Z-vector equations are derived and implemented for solving the response term due to the external electrostatic potentials, and the corresponding contribution is added to the energy gradients in the framework of the fragment molecular orbital (FMO) method. To practically solve the equations for large molecules like proteins, the equations are decoupled by taking advantage of the local nature of fragments in the FMO method and establishing the self-consistent Z-vector method. The resulting gradients are compared with numerical gradients for the test molecular systems: (H 2 O) 64 , alanine decamer, hydrated chignolin with the protein data bank (PDB) ID of 1UAO, and a Trp-cage miniprotein construct (PDB ID: 1L2Y). The computation time for calculating the response contribution is comparable to or less than that of the FMO selfconsistent charge calculation. It is also shown that the energy gradients for the electrostatic dimer approximation are fully analytic, which significantly reduces the computational costs. The fully analytic FMO gradient is parallelized with an efficiency of about 98% on 32 nodes. KeywordsPolymers, Electrostatics, Chemical bonds, Proteins, Density functional theory Disciplines Chemistry CommentsThe following article appeared in Journal of Chemical Physics 134 (2011) The Z-vector equations are derived and implemented for solving the response term due to the external electrostatic potentials, and the corresponding contribution is added to the energy gradients in the framework of the fragment molecular orbital (FMO) method. To practically solve the equations for large molecules like proteins, the equations are decoupled by taking advantage of the local nature of fragments in the FMO method and establishing the self-consistent Z-vector method. The resulting gradients are compared with numerical gradients for the test molecular systems: (H 2 O) 64 , alanine decamer, hydrated chignolin with the protein data bank (PDB) ID of 1UAO, and a Trp-cage miniprotein construct (PDB ID: 1L2Y). The computation time for calculating the response contribution is comparable to or less than that of the FMO self-consistent charge calculation. It is also shown that the energy gradients for the electrostatic dimer approximation are fully analytic, which significantly reduces the computational costs. The fully analytic FMO gradient is parallelized with an efficiency of about 98% on 32 nodes.

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Section: Computational Detailsmentioning

confidence: 99%

Section: Computational Detailsmentioning

confidence: 99%

Section: Computational Detailsmentioning

confidence: 99%

Section: Computational Detailsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Fully analytic energy gradient in the fragment molecular orbital method

Brorsen¹,

Fedorov²

2011

The Journal of Chemical Physics

100

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Quantum Mechanics in Structure‐Based Ligand Design

Söderhjelm¹,

Genheden²,

Ryde³

2012

Protein‐Ligand Interactions

141

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Catalytic Oxidative Carbonylation of Amino Moieties to Ureas, Oxamides, 2‐Oxazolidinones, and Benzoxazolones

et al. 2015

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The direct syntheses of ureas, oxamides, 2-oxazolidinones, and benzoxazolones by the oxidative carbonylation of amines, β-amino alcohols, and 2-aminophenols allows us to obtain high value added molecules, which have a large number of important applications in several fields, from very simple building blocks. We have found that it is possible to perform these transformations using the PdI2 /KI catalytic system in an ionic liquid, such as 1-butyl-3-methylimidazolium tetrafluoroborate, as the solvent, the solvent/catalyst system can be recycled several times with only a slight loss of activity, and the product can be recovered easily by crystallization.

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Novel Quantitative Structure-Activity Studies of HIV-1 Protease Inhibitors of the Cyclic Urea Type Using Descriptors Derived from Molecular Dynamics and Molecular Orbital Calculations

Cited by 36 publications

References 0 publications

Fully analytic energy gradient in the fragment molecular orbital method

Fully analytic energy gradient in the fragment molecular orbital method

Quantum Mechanics in Structure‐Based Ligand Design

Catalytic Oxidative Carbonylation of Amino Moieties to Ureas, Oxamides, 2‐Oxazolidinones, and Benzoxazolones

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