Empirical force fields for peptides and water molecules

Proteins and water molecules are major concerns in biological systems, and an accurate description of these systems has been a great challenge in computational chemistry. The development of an accurate and reliable force field for proteins and water molecules is a central objective of molecular modeling since the systems of interest are too large to be treated by quantum mechanical methods. Molecular mechanics is thus invariably used to carry out calculations on systems containing a large number of atoms.; Ion pair interactions in aqueous solution and the role of explicit water molecules have been investigated using ab initio self-consistent reaction field (SCRF) calculations with and without some explicit water molecules. The results suggest that the inclusion of explicit water molecules on hydrogen bonding sites on a solute, and the use of a continuum model to complete the hydration environment, is more accurate than a continuum model alone. This work provides useful information for understanding ion pair interactions in aqueous solution for the further development of a water potential energy function.; Two major obstacles in current force field development are inclusion of a polarization effect into a force field and calculation of geometry-dependent net atomic charges. Artificial neural networks were introduced to a water force field to represent the many-body polarization effects. Monte Carlo simulations in the isothermal-isobaric (NPT) ensemble were carried out with the force field and the result shows good agreement with structural and physical properties from experimental data.; The calculation of geometry-dependent net atomic charges was achieved based on a partial equalization of orbital electronegativity (PEOE) method by introducing bond-distance dependent damping factors. The dipole moment calculated with these charges shows good agreement with experimental data.; A new approach to develop a force field for peptides and proteins was suggested. In this approach, the parameters for nonbonded interactions were derived from ab initio calculations of polypeptides rather than from crystal packing studies of small organic molecules. The conformational preferences from the new force field are consistent with the ab initio calculations and better than conventional methods. Analysis of the force fields is made based on conformational propensity rather than on an energy comparison. This analysis provides more useful information for verification and development of a force field.