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

Here, we perform structural, thermodynamic, and kinetics tests of the Kirkwood-Buff-derived force field, KBFF20, for peptides and proteins developed in the previous article. The physical/structural tests measure the ability of KBFF20 to capture the experimental -couplings for small peptides, to keep globular monomeric and oligomeric proteins folded, and to produce the experimentally relevant expanded conformational ensembles of intrinsically disordered proteins. The thermodynamic-based tests probe KBFF20's ability to quantify the preferential interactions of sodium chloride around native β-lactoglobulin and urea around native lysozyme, to reproduce the melting curves for small helix- and sheet-based peptides, and to fold the small proteins Trp-cage and Villin.

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.

Experimental triplet and quadruplet fluctuation densities and spatial distribution function integrals for pure liquids.

Fluctuation solution theory has provided an alternative view of many liquid mixture properties in terms of particle number fluctuations. The particle number fluctuations can also be related to integrals of the corresponding two body distribution functions between molecular pairs in order to provide a more physical picture of solution behavior and molecule affinities. Here, we extend this type of approach to provide expressions for higher order triplet and quadruplet fluctuations, and thereby integrals over the corresponding distribution functions, all of which can be obtained from available experimental thermodynamic data.

Theory and Simulation of Multicomponent Osmotic Systems.

Most cellular processes occur in systems containing a variety of components many of which are open to material exchange. However, computer simulations of biological systems are almost exclusively performed in systems closed to material exchange. In principle, the behavior of biomolecules in open and closed systems will be different.