Development of Molecular Dynamics Techniques for the Study of Water and Biochemical Systems

This dissertation comprises a body of research in the field of classical molecular simulations, with particular emphasis placed on the proper depiction of water. It is arranged such that the techniques and models are first developed and tested before being applied and compared with experimental results. Accordingly, the first chapter starts by introducing the technique of molecular dynamics and discussing technical considerations needed to correctly perform molecular simulations. The second chapter builds on these consideration aspects by discussing correction techniques for handling long-ranged electrostatic interactions. Particular focus is placed on the damped shifted force (SF) technique, and it is shown to be nearly equivalent to the Ewald summation in simulations of condensed phases. Since the SF technique is pairwise, it scales as O(N) and lacks periodicity artifacts. This technique is extended to include point-multipoles, and optimal damping parameters are determined to ensure proper depiction of the dielectric behavior of molecular systems. The third chapter applies the above techniques and focuses on water model development, specifically the single-point soft sticky dipole (SSD) model. In order to better depict water with SSD in computer simulations, it needed to be reparametrized, resulting in SSD/RF and SSD/E, new variants optimized for simulations with and without a reaction field correction. These new single-point models are more efficient than the more common multi-point models and better capture the dynamic properties of water. SSD/RF can be used with damped SF through the multipolar extension described in the previous chapter. The final chapter deals with a unique polymorph of ice that was discovered while performing simulations with the SSD models. This form of ice, called imaginary ice (Ice-i), has a low-density structure which is different from any previously known ice polymorph. The free energy analysis discussed here shows that it is the thermodynamically preferred form of ice for both the single-point and commonly used multi-point water models. Including electrostatic corrections is necessary to obtain more realistic results; however, the free energies of the studied polymorphs are typically so similar that system properties, like the volume in NVT simulations, can directly influence the ice polymorph expressed.