Cardiomyopathy Mutations in Actomyosin: A Tertiary Structure Dynamics Approach within an in Silico Optical Trap Experiment

Abstract

We present a new approach to computer modeling of solvation free energies of oil in water. Informed by the behavior of TIP3P waters around simple Lennard-Jones spheres, Semi-Explicit assembly is a fast implicit approach for computing the nonpolar solvation properties of arbitrary solutes. By summing interactions from whole regions of the solute molecule, this method solves problems that appear as nonadditivities in traditional g A approaches. Semi-Explicit assembly involves little parameter fitting because the solute and water properties come from existing force fields. We test the predictions on alkanes, alkynes, linear and planar polyaromatic hydrocarbons, and on a general set of 504 molecules previously explored by explicit solvent simulations. We find that not all hydrocarbons are the same. Hydrocarbons have 'hot spots', places where firstshell waters interact more strongly with the molecule than at other locations. By accounting for these 'hot spots', Semi-Explicit assembly attains the physical accuracies of explicit solvent models, but because of the pre-computations and the regional additivities, it is nearly as fast to compute as g A methods.