Unsolved problem of long-range interactions: dipolar spin-ice study.

Long-range interactions derive various strange phenomena. As illustrated by cutoff simulations of water, increasing cutoff length does not improve the simulation result necessarily; on the contrary, it makes the result worse. In the extreme situation, the structure of water transforms into a layer structure.

Dielectric continuum model examination of real-space electrostatic treatments.

Electrostatic interaction is long ranged; thus, the accurate calculation is not an easy task in molecular dynamics or Monte Carlo simulations. Though the rigorous Ewald method based on the reciprocal space has been established, real-space treatments have recently become an attractive alternative because of the efficient calculation. However, the construction is not yet completed and is now a challenging subject.

Water access and ligand dissociation at the binding site of proteins.

Although water is undoubtedly an essential mediator of protein-ligand interactions, whether or not such water molecules are critical for the progress of ligand dissociation remains unclear. To gain a more complete understanding, molecular dynamics simulations are performed with two molecular systems, rigid model binding sites and trypsin-benzamidine. Free-energy landscapes are calculated with a suitably chosen solvent coordinate, which well describes water access to the ligand binding site.

On the ion-pair dissociation mechanisms in the small NaCl·(H O) cluster: A perspective from reaction path search calculations.

We performed reaction path search calculations for the NaCl·(H O) cluster using the global reaction route mapping (GRRM) code to understand the atomic-level mechanisms of the NaCl → Na  + Cl ionic dissociation induced by water solvents. Low-lying minima, transition states connecting two local minima and corresponding intrinsic reaction coordinates on the potential energy surface are explored. We found that the NaCl distances at the transitions states for the dissociation pathways were distributed in a relatively wide range of 2.

Distinct dissociation kinetics between ion pairs: Solvent-coordinate free-energy landscape analysis.

Different ion pairs exhibit different dissociation kinetics; however, while the nature of this process is vital for understanding various molecular systems, the underlying mechanism remains unclear. In this study, to examine the origin of different kinetic rate constants for this process, molecular dynamics simulations were conducted for LiCl, NaCl, KCl, and CsCl in water. The results showed substantial differences in dissociation rate constant, following the trend kLiCl < kNaCl < kKCl < kCsCl.

Dissociation free-energy profiles of specific and nonspecific DNA-protein complexes.

DNA-binding proteins recognize DNA sequences with at least two different binding modes: specific and nonspecific. Experimental structures of such complexes provide us a static view of the bindings. However, it is difficult to reveal further mechanisms of their target-site search and recognition only from static information because the transition process between the bound and unbound states is not clarified by static information.

What determines water-bridge lifetimes at the surface of DNA? Insight from systematic molecular dynamics analysis of water kinetics for various DNA sequences.

The lifetime during which a water molecule resides at the surface of a biomolecule varies according to the hydration site. What determines this variety of lifetimes? Despite many previous studies, there is still no uniform picture quantitatively explaining this phenomenon. Here we calculate the lifetime for a particular hydration pattern in the DNA minor groove, the water bridge, for various DNA sequences to show that the water-bridge lifetime varies from 1 to ~300ps in a sequence-dependent manner.

Enhanced resolution of molecular recognition to distinguish structurally similar molecules by different conformational responses of a protein upon ligand binding.

MutT distinguishes substrate 8-oxo-dGTP from dGTP and also 8-oxo-dGMP from dGMP despite small differences of chemical structures between them. In this paper we show by the method of molecular dynamics simulation that the transition between conformational substates of MutT is a key mechanism for a high-resolution molecular recognition of the differences between the very similar chemical compounds. (1) The native state MutT has two conformational substates with similar free energies, each characterized by either open or closed of two loops surrounding the substrate binding active site.

Molecular dynamics free energy calculations to assess the possibility of water existence in protein nonpolar cavities.

Are protein nonpolar cavities filled with water molecules? Although many experimental and theoretical investigations have been done, particularly for the nonpolar cavity of IL-1 beta, the results are still conflicting. To study this problem from the thermodynamic point of view, we calculated hydration free energies of four protein nonpolar cavities by means of the molecular dynamics thermodynamic integration method. In addition to the IL-1 beta cavity (69 A(3)), we selected the three largest nonpolar cavities of AvrPphB (81 A(3)), Trp repressor (87 A(3)), and hemoglobin (108 A(3)) from the structural database, in view of the simulation result from another study that showed larger nonpolar cavities are more likely to be hydrated.

Sequence dependencies of DNA deformability and hydration in the minor groove.

DNA deformability and hydration are both sequence-dependent and are essential in specific DNA sequence recognition by proteins. However, the relationship between the two is not well understood. Here, systematic molecular dynamics simulations of 136 DNA sequences that differ from each other in their central tetramer revealed that sequence dependence of hydration is clearly correlated with that of deformability.

Comparison of DNA hydration patterns obtained using two distinct computational methods, molecular dynamics simulation and three-dimensional reference interaction site model theory.

Because proteins and DNA interact with each other and with various small molecules in the presence of water molecules, we cannot ignore their hydration when discussing their structural and energetic properties. Although high-resolution crystal structure analyses have given us a view of tightly bound water molecules on their surface, the structural data are still insufficient to capture the detailed configurations of water molecules around the surface of these biomolecules. Thanks to the invention of various computational algorithms, computer simulations can now provide an atomic view of hydration.

Liquid water simulation: a critical examination of cutoff length.

Cutoff treatment is the simplest approach for evaluating intermolecular interactions in molecular dynamics simulations. It has been believed that increasing cutoff length makes simulation results better. On the contrary, our results of the bulk water simulations studied within the range of cutoff lengths, 9-18 A, showed an opposite tendency: the artifact was enhanced by increasing the cutoff length.

Centroid molecular dynamics approach to the transport properties of liquid para-hydrogen over the wide temperature range.

Fundamental transport properties of liquid para-hydrogen (p-H(2)), i.e., diffusion coefficients, thermal conductivity, shear viscosity, and bulk viscosity, have been evaluated by means of the path integral centroid molecular dynamics (CMD) calculations.