The zero-multipole summation method for estimating electrostatic interactions in molecular dynamics : Analysis of the accuracy and application to liquid systems

The following article appeared in J. Chem. Phys. 140, 194307 (2014) and may be found at http://scitation.aip.org/content/aip/journal/jcp/140/19/10.1063/1.487569

Simple and accurate scheme to compute electrostatic interaction : Zero-dipole summation technique for molecular system and application to bulk water

The following article appeared in J. Chem. Phys. 137, 054314 (2012) and may be found at http://scitation.aip.org/content/aip/journal/jcp/137/5/10.1063/1.473978

Exploring ligand binding pathways on proteins using hypersound-accelerated molecular dynamics

生体分子の動きを効率的に捉えるシミュレーション技術を開発 --超高周波超音波照射によってタンパク質と医薬品の結合計算を加速--. 京都大学プレスリリース. 2021-05-28.Capturing the dynamic processes of biomolecular systems in atomistic detail remains difficult despite recent experimental advances. Although molecular dynamics (MD) techniques enable atomic-level observations, simulations of “slow” biomolecular processes (with timescales longer than submilliseconds) are challenging because of current computer speed limitations. Therefore, we developed a method to accelerate MD simulations by high-frequency ultrasound perturbation. The binding events between the protein CDK2 and its small-molecule inhibitors were nearly undetectable in 100-ns conventional MD, but the method successfully accelerated their slow binding rates by up to 10–20 times. Hypersound-accelerated MD simulations revealed a variety of microscopic kinetic features of the inhibitors on the protein surface, such as the existence of different binding pathways to the active site. Moreover, the simulations allowed the estimation of the corresponding kinetic parameters and exploring other druggable pockets. This method can thus provide deeper insight into the microscopic interactions controlling biomolecular processes

NMR Characterization of the Interaction of the Endonuclease Domain of MutL with Divalent Metal Ions and ATP

Mizushima R, Kim JY, Suetake I, Tanaka H, Takai T, et al. (2014) NMR Characterization of the Interaction of the Endonuclease Domain of MutL withDivalent Metal Ions and ATP. PLoS ONE 9(6): e98554. doi:10.1371/journal.pone.009855

NMR Characterization of the Interaction of the Endonuclease Domain of MutL with Divalent Metal Ions and ATP

Mizushima R, Kim JY, Suetake I, Tanaka H, Takai T, et al. (2014) NMR Characterization of the Interaction of the Endonuclease Domain of MutL withDivalent Metal Ions and ATP. PLoS ONE 9(6): e98554. doi:10.1371/journal.pone.009855

Enhanced and effective conformational sampling of protein molecular systems for their free energy landscapes

Protein folding and protein–ligand docking have long persisted as important subjects in biophysics. Using multicanonical molecular dynamics (McMD) simulations with realistic expressions, i.e., all-atom protein models and an explicit solvent, free-energy landscapes have been computed for several systems, such as the folding of peptides/proteins composed of a few amino acids up to nearly 60 amino-acid residues, protein–ligand interactions, and coupled folding and binding of intrinsically disordered proteins. Recent progress in conformational sampling and its applications to biophysical systems are reviewed in this report, including descriptions of several outstanding studies. In addition, an algorithm and detailed procedures used for multicanonical sampling are presented along with the methodology of adaptive umbrella sampling. Both methods control the simulation so that low-probability regions along a reaction coordinate are sampled frequently. The reaction coordinate is the potential energy for multicanonical sampling and is a structural identifier for adaptive umbrella sampling. One might imagine that this probability control invariably enhances conformational transitions among distinct stable states, but this study examines the enhanced conformational sampling of a simple system and shows that reasonably well-controlled sampling slows the transitions. This slowing is induced by a rapid change of entropy along the reaction coordinate. We then provide a recipe to speed up the sampling by loosening the rapid change of entropy. Finally, we report all-atom McMD simulation results of various biophysical systems in an explicit solvent