title: Multiscale Reactive Molecular Dynamics for Absolute pKaPredictions and Amino Acid Deprotonation.
abstract: Accurately calculating a weak acid's pKafrom simulations remains a challenging task. We report a multiscale theoretical approach to calculate the free energy profile for acid ionization, resulting in accurate absolute pKavalues 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 pKa) 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 pKavalues and provide ample statistics to probe the molecular mechanism of dissociation. This analysis shows changes in the solvation structure and Zundel-dominated transitions between the protonated acid, contact ion pair, and bulk solvated excess proton.
authors: Department of Chemistry, Institute for Biophysical Dynamics, and Computation Institute, University of Chicago , 5735 S. Ellis Ave., Chicago, Illinois 60637, United States.
authors: J Gard
authors: JG
authors: Nelson
authors: Department of Chemistry, Institute for Biophysical Dynamics, and Computation Institute, University of Chicago , 5735 S. Ellis Ave., Chicago, Illinois 60637, United States.
authors: Yuxing
authors: Y
authors: Peng
authors: Department of Chemistry, Institute for Biophysical Dynamics, and Computation Institute, University of Chicago , 5735 S. Ellis Ave., Chicago, Illinois 60637, United States.
authors: Daniel W
authors: DW
authors: Silverstein
authors: Department of Chemistry, Institute for Biophysical Dynamics, and Computation Institute, University of Chicago , 5735 S. Ellis Ave., Chicago, Illinois 60637, United States.
authors: Jessica M J
authors: JM
authors: Swanson