Hybrid method for representing ions in implicit solvation calculations

Abstract

Fast and accurate calculations of the electrostatic features of highly charged biomolecules such as DNA, RNA, and highly charged proteins are crucial and challenging tasks. Traditional implicit solvent methods calculate the electrostatic features quickly, but these methods are not able to balance the high net biomolecular charges effectively. Explicit solvent methods add unbalanced ions to neutralize the highly charged biomolecules in molecular dynamic simulations, which require more expensive computing resources. Here we report developing a novel method, Hybridizing Ions Treatment (HIT), which hybridizes the implicit solvent method with an explicit method to realistically calculate the electrostatic potential for highly charged biomolecules. HIT utilizes the ionic distribution from an explicit method to predict the bound ions. The bound ions are then added in the implicit solvent method to perform the electrostatic potential calculations. In this study, two training sets were developed to optimize parameters for HIT. The performance on the testing set demonstrates that HIT significantly improves the electrostatic calculations. Results on molecular motors myosin and kinesin reveal some mechanisms and explain some previous experimental findings. HIT can be widely used to study highly charged biomolecules, including DNA, RNA, molecular motors, and other highly charged biomolecules. The HIT package is available at http://compbio.utep.edu/static/downloads/download_hit.zip.