Hideaki Fujitani

Direct calculation of the binding free energies of FKBP ligands

Direct calculations of the absolute free energies of binding for eight ligands to FKBP protein were performed using the Fujitsu BioServer massively parallel computer. Using the latest version of the general assisted model building with energy refinement (AMBER) force field for ligand model parameters and the Bennett acceptance ratio for computing free-energy differences, we obtained an excellent linear fit between the calculated and experimental binding free energies. The rms error from a linear fit is 0.4 kcal/mol for eight ligand complexes. In comparison with a previous study of the binding energies of these same eight ligand complexes, these results suggest that the use of improved model parameters can lead to more predictive binding estimates, and that these estimates can be obtained with significantly less computer time than previously thought. These findings make such direct methods more attractive for use in rational drug design.

High-Level ab Initio Calculations To Improve Protein Backbone Dihedral Parameters.

We present new molecular mechanical dihedral parameters for the Ramachandran angles ϕ and ψ of a protein backbone based on high-level ab initio molecular orbital calculations for hydrogen-blocked or methyl-blocked glycine and alanine dipeptides. Fully relaxed 15° (ϕ, ψ) contour maps were calculated at the MP2/6-31G(d) level of theory. Finding out the lowest energy path for ϕ (or ψ) to change from -180° to 180° in the contour map, we performed a DF-LCCSD(T0)/Aug-cc-pVTZ//DF-LMP2/Aug-cc-pVTZ level calculation to get the torsional energy profiles of ϕ (or ψ). Molecular mechanical torsion profiles with AMBER force field variants significantly differed from the ab initio profiles, so we derived new molecular mechanical dihedral parameters of a protein backbone to fit the ab initio profiles.

LMTO-ASA Calculations on Si/NiSi2 Interfaces

LMTO-ASA (linear muffin-tin orbital atomic-sphere approximation) calculations were performed for Si(111)/NiSi 2 (111) interfaces. The perfect epitaxial structure (type A) has lower Schottky barrier heights and higher total energy than the 180° rotated structure (type B).

Electronic structure of Si/disilicide interfaces

Abstract Using supercells, the electronic structures of Si(111)/CoSi 2 and Si(111)/NiSi 2 interfaces are studied by the linear muffin-tin orbital atomic sphere approximation method (LMTO-ASA). Schottky barrier heights (SBHs) are strongly correlated with the interface atomic structures and are determined mainly by interface bonding states and the screening effect of the semiconductor. Metal-induced gap states (MIGS) are metal wave function tails caused by the Schottky barriers.

Docking study and binding free energy calculation of poly (ADP-ribose) polymerase inhibitors.

Recently, the massively parallel computation of absolute binding free energy with a well-equilibrated system (MP-CAFEE) has been developed. The present study aimed to determine whether the MP-CAFEE method is useful for drug discovery research. In the drug discovery process, it is important for computational chemists to predict the binding affinity accurately without detailed structural information for protein / ligand complex. We investigated the absolute binding free energies for Poly (ADP-ribose) polymerase-1 (PARP-1) / inhibitor complexes, using the MP-CAFEE method. Although each docking model was used as an input structure, it was found that the absolute binding free energies calculated by MP-CAFEE are well consistent with the experimental ones. The accuracy of this method is much higher than that using molecular mechanics Poisson-Boltzmann / surface area (MM / PBSA). Although the simulation time is quite extensive, the reliable predictor of binding free energies would be a useful tool for drug discovery projects.

Calculated electronic structure at the CaF2/Si(111) interface

The electronic structure of the CaF2/Si(111) interface is studied using the linear muffin-tin orbitals in the atomic sphere approximation within the local density approximation. This involves three structural models of the interface: For the model with sevenfold coordinated Ca atoms at the interface, the Fermi level is pinned by interface states originating in dangling bond from the interfacial Si atom. For models with a CaF layer at the interface, interface states in the Si band gap separate into occupied and unoccupied states. The energy dispersion calculated for the occupied interface states of the model with the interfacial Ca atom at the T4 site agrees better with angle-resolved photoelectron spectroscopy data than that of the model with the Ca atom at the H3 site.

Schottky barriers at epitaxial silicide/Si interfaces

Abstract We studied the electronic structure of the YSi2/Si(111) and NiSi2/Si(001) interfaces using the linear muffin in orbitals in the atomic sphere approximation (LMTO-ASA) based on the local density approximation (LDA). Together with the previous results on the CoSi2/Si(111) and NiSi2/Si(111) interfaces, we showed that LMTO-ASA calculations with a large supercell give an adequate Schottky barrier height (SBH: EF −: EV) for real silicide/Si interfaces although the LDA depresses the band gap of bulk Si to almost half of the experimental value. An eightfold NiSi2/Si(001) interface showed almost the same SBH as the type A NiSi2/Si(111) interface. From the relation between the interface structure and the calculated SBH, we speculate that the bond angle at the interface affects the SBH

LMTO-ASA Calculations on NiSi2/Si(001) Interface

The electronic structure of the NiSi 2 /Si(001) interface was studied using LMTO-ASA (linear muffin-tin orbitals in the atomic sphere approximation) based on the density functional formalism. We examined two interface structures in which the Ni atoms at the interface are sixfold-coordinated or eightfold-coordinated. The sixfold structure had a negative Schottky barrier height ( E f - E υ ). The eightfold NiSi 2 /Si(001) structure showed almost the same Schottky barrier height as the Type-A NiSi 2 /Si(111) interface despite the difference in the interface atomic structure.

Self-consistent kinetic lattice Monte Carlo

The authors present a brief description of a formalism for modeling point defect diffusion in crystalline systems using a Monte Carlo technique. The main approximations required to construct a practical scheme are briefly discussed, with special emphasis on the proper treatment of charged dopants and defects. This is followed by tight binding calculations of the diffusion barrier heights for charged vacancies. Finally, an application of the kinetic lattice Monte Carlo method to vacancy diffusion is presented.