PMFF: Development of a Physics-Based Molecular Force Field for Protein Simulation and Ligand Docking.

The physics-based molecular force field (PMFF) was developed by integrating a set of potential energy functions in which each term in an intermolecular potential energy function is derived based on experimental values, such as the dipole moments, lattice energy, proton transfer energy, and X-ray crystal structures. The term "physics-based" is used to emphasize the idea that the experimental observables that are considered to be the most relevant to each term are used for the parameterization rather than parameterizing all observables together against the target value. PMFF uses MM3 intramolecular potential energy terms to describe intramolecular interactions and includes an implicit solvation model specifically developed for the PMFF. We evaluated the PMFF in three ways. We concluded that the PMFF provides reliable information based on the structure in a biological system and interprets the biological phenomena accurately by providing more accurate evidence of the biological phenomena.

Common features of orientational order at the temperature of maximum density for various water models: molecular dynamics study.

Canonical ensembles for liquid water were obtained from molecular dynamics simulations at various temperatures using the TIP5P, TIP4P-FQ, TIP4P, and SPC/E water models at a fixed density of 1 g/cm3. From these ensembles, it was found that the distributions of the orientational order parameter q of these models showed similar patterns as temperature changed except that the distributions were shifted relative to each other by the difference of their temperature of maximum density (TMD). The four models exhibited similar distributions and average values of orientational order around their respective TMDs, and these common features were investigated in detail especially. The current study suggests that the unique microscopic configuration of water molecules cause TMD phenomenon in any reasonable water model. This finding provides a useful tool in the development of new water potentials by offering guidelines to predict the TMD, avoiding troublesome isothermal-isobaric ensemble simulations.

Conformational study of the trinucleotide CpGpCp-pentapeptide Gly5 complex: The important role of bridging water in the complex formation.

Conformational changes in the RNA-protein interaction were studied by calculating the intramolecular interaction energy of a model complex with the use of potential functions. The model complex has hydrogen-bonded water molecules bridging polypeptide NH groups to 2'-hydroxyl groups and sugar ring oxygen atoms. Since the sugar ring is constrained by the bridging water, preliminary calculations with the model compounds, the sugar ring, mononucleoside diphosphates, pCp and pGp, were carried out, and the flexibility and energetics of the sugar ring were compared with the previous results of DNA. The shift of the phase angle of the sugar ring occurred in the complex formation because of the hydrogen bond through the bridging water and the flexibility of the sugar ring. The free energy difference at 298 K is about -74.0 kcal/mol which was obtained from the intramolecular interaction energy difference of -67.5 kcal/mol by adding the conformational entropy change of 21.9 e.u., which in turn was calculated from the evaluation of the determinant of the matrix containing variances and covariances of the internal coordinates.

The structure of water near platinum and its significance in water-adsorbent system: molecular dynamics study.

Water structure around hydrophilic adsorbents is expected to differ from normal water structure. In some cases, a change of water structure seems to significantly affect phenomena involved in water-adsorbent systems. To investigate this, we have performed molecular dynamic simulations of three systems, water between (111) surfaces of Pt, water between (100) surfaces of Pt, and pure water at 298 K. For the analysis of water structure, we concentrated on the five-membered ring (R5) structure and six-membered ring (R6) structure, which are the most probable in nature. For both (111) and (100) of Pt, the ratio of hexameric ring/pentameric ring (R6/R5) in semibound regions was higher than that of bulk water, as expected. The function of adsorbent ceramics was explained in terms of the change of water structure when they are used as biomaterials, support materials, etc. The obscure mechanisms for the effects of medicine stones, antioxidants, etc., were also discussed from this point of view.