Theory for polarizable, pH-coupled molecular dynamics for applications to protein mechanisms and design

Carefully crafted computer simulations could measure many experimental products before they are made in the laboratory so that only the most promising trials would need to be conducted physically by researchers. Multitudes of drug formulations, synthetic proteins, or other molecules could have their properties assessed quickly to accelerate research. The difficulty lies in creating a realistic picture of the chemistry in the computer simulation. Previous computational models that have incorporated pH effects have neglected to describe electrostatic past simplistic atomic partial charges. These systems then do not respond to their environment as reality dictates. This work provides the theory to implement pH effects with an advanced description of electrostatics that includes how clouds of electrons spread out and orient themselves in response to electric fields. The theory is then tested against real biological systems and success over the previous models is demonstrated. In sum, this work opens the door for the most advanced computational model for protein design.