Kirkwood-Buff-Derived Force Field for Peptides and Proteins: Philosophy and Development of KBFF20.

A new classical nonpolarizable force field, KBFF20, for the simulation of peptides and proteins is presented. The force field relies heavily on the use of Kirkwood-Buff theory to provide a comparison of simulated and experimental Kirkwood-Buff integrals for solutes containing the functional groups common in proteins, thus ensuring intermolecular interactions that provide a good balance between the peptide-peptide, peptide-solvent, and solvent-solvent distributions observed in solution mixtures. In this way, it differs significantly from other biomolecular force fields.

A Kirkwood-Buff derived force field for alkaline earth halide salts.

The activity and function of many macromolecules in cellular environments are coupled with the binding of divalent ions such as calcium or magnesium. In principle, computer simulations can be used to understand the molecular level aspects of how many important macromolecules interact with ions. However, most of the force fields currently available often fail to accurately reproduce the properties of divalent ions in aqueous environments.

A Kirkwood-Buff Derived Force Field for Aqueous Alkali Halides.

A classical nonpolarizable force field is presented for the simulation of aqueous alkali halide solutions (MX), where M = Li(+), Na(+), K(+), Rb(+), Cs(+) and X = F(-), Cl(-), Br(-), I(-), and their interactions with biomolecules. The models are specifically designed to reproduce the experimental Kirkwood-Buff integrals, and thereby the solution salt activities, as a function of salt concentration. Additionally, we demonstrate that these models reasonably reproduce other experimental properties including ion diffusion constants, dielectric decrements, and the excess heats of mixing.

Kirkwood-Buff integrals for ideal solutions.

The Kirkwood-Buff (KB) theory of solutions is a rigorous theory of solution mixtures which relates the molecular distributions between the solution components to the thermodynamic properties of the mixture. Ideal solutions represent a useful reference for understanding the properties of real solutions. Here, we derive expressions for the KB integrals, the central components of KB theory, in ideal solutions of any number of components corresponding to the three main concentration scales.

Developing Force Fields from the Microscopic Structure of Solutions.

We have been developing force fields designed for the eventual simulation of peptides and proteins using the Kirkwood-Buff (KB) theory of solutions as a guide. KB theory provides exact information on the relative distributions for each species present in solution. This information can also be obtained from computer simulations.

A Kirkwood-Buff derived force field for thiols, sulfides, and disulfides.

A force field has been developed for molecular simulations of methanethiol, dimethyl sulfide, and dimethyl disulfide mixtures. The force field specifically attempts to balance the solvation and self-association of these solutes in solution mixtures with methanol. The force field is based on the Kirkwood-Buff (KB) theory of solutions and is parametrized using the KB integrals obtained from the experimental activity coefficients for the solution mixtures.

Droplet deformation in dc electric fields: the extended leaky dielectric model.

The leaky dielectric model (LDM) was extended to large droplet distortions in dc electric fields. The resulting extended LDM (ELDM) reduces to the LDM for small droplet aspect ratios and to the pure dielectric model when the ratio of droplet and matrix conductivities equals the inverse ratio of their permittivities. The ELDM distinguishes between two types of phenomena possible at high electric fields: continuous deformation and hysteresis.