Akifumi Oda

Here, the comparisons of performance of nine consensus scoring strategies, in which multiple scoring functions were used simultaneously to evaluate candidate structures for a protein-ligand complex, in combination with nine scoring functions (FlexX score, GOLD score, PMF score, DOCK score, ChemScore, DrugScore, PLP, ScreenScore, and X-Score), were carried out. The systematic naming of consensus scoring strategies was also proposed. Our results demonstrate that choosing the most appropriate type

The heme protein, cytochrome P450, is an oxidoreductase that plays an important role in drug metabolism. To model P450s using molecular mechanics methods and classical molecular dynamics simulations, force field parameters and atomic charges are required. Because these parameters are generally obtained by quantum chemical methods, an appropriate simplified model for the iron-porphyrin system was needed. In this study, two models with a five-coordinated Fe(III) mimicking the sextet spin state of

Although various higher-order protein structure prediction methods have been developed, almost all of them were developed based on the three-dimensional (3D) structure information of known proteins. Here we predicted the short protein structures by molecular dynamics (MD) simulations in which only Newton's equations of motion were used and 3D structural information of known proteins was not required. To evaluate the ability of MD simulationto predict protein structures, we calculated seven short

Many natural mutants of the drug metabolizing enzyme cytochrome P450 (CYP) 2D6 have been reported. Because the enzymatic activities of many mutants are different from that of the wild type, the genetic polymorphism of CYP2D6 plays an important role in drug metabolism. In this study, the molecular dynamics simulations of the wild type and mutants of CYP2D6, CYP2D6.1, 2, 10, 14A, 51, and 62 were performed, and the predictions of static and dynamic structures within them were conducted. In the muta

Abstract We evaluated the docking accuracy of ArgusLab, which is a freely available software program for computational docking, using experimentally determined protein–ligand complex structures. Investigations of the roles of parameters used for docking calculations in ArgusLab were carried out in addition to evaluation of the software. The results indicate that one docking engine of ArgusLab, GADock, is superior in terms of accuracy, and that another docking engine, ArgusDock, is advantageous i

In this study, we investigated the influence of single nucleotide polymorphisms on the conformation of mutated cytochrome P450 (CYP) 2B6 proteins using molecular dynamics (MD) simulation. Some of these mutations influence drug metabolism activities, leading to individual variations in drug efficacy and pharmacokinetics. Using computational docking, we predicted the structure of the complex between the antimalarial agent artemether and CYP2B6 whose conformations were obtained by MD simulation. Th

We conducted a docking efficiency validation of ArgusLab, a free docking software program. In this study, the calculated binding free energies of protein-ligand complexes by scoring functions were compared with experimental binding affinities. Correlations between the calculated and experimental data were evaluated for 11 ArgusLab settings and compared. Our results indicate that ArgusLab is useful for virtual screening and the weight of van der Waals interactions are unimportant for binding free

We evaluated the pocket-searching abilities of the computer programs HBOP and HBSITE, in which hydrophobic potentials calculated on grid points generated around a protein function as an indicator of the pocket-like property-using a test set of 458 experimentally observed structures of protein-ligand complexes. The results were compared with those obtained using the alternative algorithms PASS and SiteID, which only consider geometric properties, and Q-SiteFinder, which considers not only geometr

Molecular-dynamics simulations of amyloid-beta(1-42) peptides including D-aspartic acid residues were performed, and their three-dimensional structures were compared. The simulations were performed in an aqueous environment using a continuous solvent model. In the structures obtained from simulations, the occurrence ratio of beta-extended structures for the peptide that included D-Asp23 was larger than that for the wild-type peptide. These beta-extended structures appeared in the C-terminal regi