AMOEBA 2.0: A physics-first approach to biomolecular simulations

The goal of the AMOEBA force field project is to use classical physics to understand and predict the nature of interactions between biological molecules.~ While making significant advances over the past decade, the ultimate goal of predicting binding energies with ``chemical accuracy'' remains elusive.~ The primary source of this inaccuracy comes from the physics of how molecules interact at short range.~ For example, despite AMOEBA's advanced treatment of electrostatics, the force field dramatically overpredicts the electrostatic energy of DNA stacking interactions.~ AMOEBA 2.0 works to correct these errors by including simple, first principles physics-based terms to account for the quantum mechanical nature of these short-range molecular interactions.~ We have added a charge penetration term that considerably improves the description of electrostatic interactions at short range.~ We are reformulating the polarization term of AMOEBA in terms of basic physics assertions.~ And we are reevaluating the van der Waals term to match \textit{ab initio} energy decompositions.~ These additions and changes promise to make AMOEBA more predictive.~ By including more physical detail of the important short-range interactions of biological molecules, we hope to move closer to the ultimate goal of true predictive power.