The long-range correction (LC) scheme for the exchange functional of density-functional theory (DFT) was combined with the coupled-perturbed Kohn-Sham (CPKS) method to calculate nonlinear optical response properties. By using this LC-CPKS method, we calculated the hyperpolarizabilities of typical molecules and the dipole moments, polarizabilities, and hyperpolarizabilities of push-pull pi-conjugated systems: p-nitroaniline, 4-amino-4'-nitrostilbene, and alpha,omega-nitroaminopolyenes. It was found that the LC scheme clearly improved the calculation of these optical properties for all of these systems, which have been significantly overestimated by conventional DFTs. We therefore concluded that the long-range exchange interaction played an important role in calculating the optical properties using the DFT formalism.

The applicability of density functional theory (DFT) to van der Waals (vdW) calculations are investigated by using the long-range exchange correction scheme and the Andersson–Langreth–Lundqvist vdW functional. By calculating bond energy potentials of rare-gas dimers, it was found that the present scheme gives much more accurate potentials for all dimers than conventional sophisticated DFT methods do. We therefore confirmed that vdW bonds are constructed under the balance of long-range exchange and vdW correlation interactions, although neither of these interactions are usually contained in pure exchange–correlation functionals. It was also found that calculated vdW potentials are obviously affected by functional forms for rapidly varying densities. Especially in vdW calculations, we must employ a correlation functional that satisfies the fundamental condition for rapidly varying density.

Two critical extensions to our fast, accurate, and easy-to-implement binary or ternary interaction method for weakly interacting molecular clusters [S. Hirata et al., Mol. Phys. 103, 2255 (2005)] have been proposed, implemented, and applied to water hexamers, hydrogen fluoride chains and rings, and neutral and zwitterionic glycine-water clusters with an excellent initial performance assessment result. Our original method included up to two- or three-body Coulomb, exchange, and correlation energies exactly and higher-order Coulomb energies in the dipole-dipole interaction approximation. In this work, the dipole moments are replaced by atom-centered point charges determined so that they reproduce the electrostatic potentials of the cluster subunits accurately and also self-consistently with one another in the cluster environment. They have been shown to lead to a dramatic improvement in the description of short-range electrostatic potentials not only of large, charge-separated subunits such as zwitterionic glycine but also of small subunits. Furthermore, basis set superposition errors (BSSEs) have been eliminated by combining the Valiron-Mayer function counterpoise (VMFC) correction with our binary or ternary interaction method. A new BSSE-correction scheme has been proposed on this basis, wherein three-body and all higher-order Coulomb effects on BSSE are also estimated. The BSSE-corrected ternary interaction method with atom-centered point charges reproduces the VMFC-corrected results within 0.1 kcal/mol. The proposed method is not only more efficient but also significantly more accurate than conventional correlation methods uncorrected of BSSE.

Polarizabilities and second hyperpolarizabilities of polyacetylene and a hydrogen chain are evaluated by density functional theory (DFT) using a hybrid generalized gradient approximation functional with correct long-range electron-electron interactions. The well known catastrophic overestimate of the hyperpolarizabilities for molecular systems of enhanced length is corrected by the two-electron repulsion operator decomposition technique, integrating the distance-dependent nonlocal exchange effects for long-range interaction, while neither the asymptotically corrected exchange functional for long-range interaction nor ordinary hybrid methods seem to be capable of overcoming the serious drawback of the DFT in polarizability/hyperpolarizability evaluation.

GENeralized-Ensemble SImulation System (GENESIS) is a software package for molecular dynamics (MD) simulation of biological systems. It is designed to extend limitations in system size and accessible time scale by adopting highly parallelized schemes and enhanced conformational sampling algorithms. In this new version, GENESIS 1.1, new functions and advanced algorithms have been added. The all-atom and coarse-grained potential energy functions used in AMBER and GROMACS packages now become available in addition to CHARMM energy functions. The performance of MD simulations has been greatly improved by further optimization, multiple time-step integration, and hybrid (CPU + GPU) computing. The string method and replica-exchange umbrella sampling with flexible collective variable choice are used for finding the minimum free-energy pathway and obtaining free-energy profiles for conformational changes of a macromolecule. These new features increase the usefulness and power of GENESIS for modeling and simulation in biological research. © 2017 Wiley Periodicals, Inc.

Enzymatic hydrolysis of nucleotide triphosphate (NTP) plays a pivotal role in protein functions. In spite of its biological significance, however, the chemistry of the hydrolysis catalysis remains obscure because of the complex nature of the reaction. Here we report a study of the molecular mechanism of hydrolysis of adenosine triphosphate (ATP) in F(1)-ATPase, an ATP-driven rotary motor protein. Molecular simulations predicted and single-molecule observation experiments verified that the rate-determining step (RDS) is proton transfer (PT) from the lytic water molecule, which is strongly activated by a metaphosphate generated by a preceding P(γ)-O(β) bond dissociation (POD). Catalysis of the POD that triggers the chain activation of the PT is fulfilled by hydrogen bonds between Walker motif A and an arginine finger, which commonly exist in many NTPases. The reaction mechanism unveiled here indicates that the protein can regulate the enzymatic activity for the function in both the POD and PT steps despite the fact that the RDS is the PT step.

Microbial opsins with a bound chromophore function as photosensitive ion transporters and have been employed in optogenetics for the optical control of neuronal activity. Molecular engineering has been utilized to create colour variants for the functional augmentation of optogenetics tools, but was limited by the complexity of the protein–chromophore interactions. Here we report the development of blue-shifted colour variants by rational design at atomic resolution, achieved through accurate hybrid molecular simulations, electrophysiology and X-ray crystallography. The molecular simulation models and the crystal structure reveal the precisely designed conformational changes of the chromophore induced by combinatory mutations that shrink its π-conjugated system which, together with electrostatic tuning, produce large blue shifts of the absorption spectra by maximally 100 nm, while maintaining photosensitive ion transport activities. The design principle we elaborate is applicable to other microbial opsins, and clarifies the underlying molecular mechanism of the blue-shifted action spectra of microbial opsins recently isolated from natural sources.

Replica-exchange molecular dynamics (REMD) and their variants have been widely used in simulations of the biomolecular structure and dynamics. Replica exchange with solute tempering (REST) is one of the methods where temperature of a pre-defined solute molecule is exchanged between replicas, while solvent temperatures in all the replicas are kept constant. REST greatly reduces the number of replicas compared to the temperature REMD, while replicas at low temperatures are often trapped under their conditions, interfering with the conformational sampling. Here, we introduce a new scheme of REST, referred to as generalized REST (gREST), where the solute region is defined as a part of a molecule or a part of the potential energy terms, such as the dihedral-angle energy term or Lennard-Jones energy term. We applied this new method to folding simulations of a β-hairpin (16 residues) and a Trp-cage (20 residues) in explicit water. The protein dihedral-angle energy term is chosen as the solute region in the simulations. gREST reduces the number of replicas necessary for good random walks in the solute-temperature space and covers a wider conformational space compared to the conventional REST2. Considering the general applicability, gREST should become a promising tool for the simulations of protein folding, conformational dynamics, and an drug design.