Implicit Solvation Using the Superposition Approximation (IS-SPA): Extension to Peptides in a Polar Solvent

Efficient, accurate, and adaptable implicit solvent models remain a significant challenge in the field of molecular simulation. A recent model, IS-SPA, based on approximating mean force using superposition approximation, provides platform to achieve these goals. IS-SPA was originally developed handle non-polar solutes TIP3P water model but can be extended accurately treat polar other solvents. In this manuscript, we demonstrate how adapt include treatment orientation long ranged electrostatics chloroform. The chloroform is approximated as that an ideal dipole aligned electrostatic field. solvent--solute then considered averaged radially symmetric Lennard-Jones component multipole expansion through octupole term. Parameters for atom-based density electric functions are fit from explicit simulations independent atoms or molecules. Using parameters, accounts asymmetry charge solvation reproduces potential dimerization two oppositely charged spheres with high fidelity. Additionally, more captures effect monomer dimer configurations alanine dipeptide than generalized Born constant dielectric model. current version algorithm expected outperform aggregation small peptides at concentrations below 150 mM, well above typical experimental materials.