Multiscale Reactive Molecular Dynamics for Absolute pK_a Predictions and Amino Acid Deprotonation.

ABSTRACT: Accurately calculating a weak acid's pK_a from simulations remains a challenging task. We report a multiscale theoretical approach to calculate the free energy profile for acid ionization, resulting in accurate absolute pK_a values in addition to insights into the underlying mechanism. Importantly, our approach minimizes empiricism by mapping electronic structure data (QM/MM forces) into a reactive molecular dynamics model capable of extensive sampling. Consequently, the bulk property of interest (the absolute pK_a) is the natural consequence of the model, not a parameter used to fit it. This approach is applied to create reactive models of aspartic and glutamic acids. We show that these models predict the correct pK_a val

SUBMITTER: Nelson JG 

PROVIDER: S-EPMC4095931 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature