Monte Carlo computer simulation of water-amino acid interactions

The sensitivity of computer simulated solvent structures to changes in both non-bonded (Lennard-Jones) coefficients and partial atomic charges has been investigated with use of amino acid hydrate crystals in which the water structure is well defined experimentally. The polarizable electropole (p.e.) model of water has been extended to describe water-protein interactions; thus, the cooperative nature of the hydrogen bond (i.e. non-pair additive effects) is allowed for through a polarizable dipole. By means of Monte Carlo calculations, the predicted water positions were found to be very sensitive to the input parameters used to define both the non-bonded and electrostatic interactions. Root mean square deviations between simulated and X-ray structures were not always adequate to describe these differences and so more detailed comparisons were made. Non-pair additive effects were shown to lead to large changes in water dipoles, the values of which depended specifically on the system under consideration.