A recent breakthrough in the Roitberg group is the development of methods that allow the theoretical study of electrochemical processes, even when pH effects also take place. These are the first implementations of constant redox potential methods in a common software package for molecular simulations. These simulations have high-performance because they can be done using AMBER’s GPU-accelerated code; GPU-accelerated calculations for our test system are 243 times faster than using a single CPU core and 24 times faster than using 16 CPU cores [1]. Our initial publication about these methods was published on a special edition of the J. Chem. Phys. [1], and made it onto the cover of the journal, which highlights the importance of these methodologies. Replica Exchange Molecular Dynamics (REMD) is a state-of-the-art technique that gives faster statistical ensemble convergence while taking advantage of computational parallelism. Our work with AMBER brings the first implementation of redox potential Replica Exchange MD (E-REMD) and it is the first work to present pH and E as options for multidimensional REMD. REMD allows converged results to be achieved with significantly fewer MD steps. In a follow-up publication, we have shown that multidimensional REMD using pH and E dimensions further enhance the convergence of one-dimensional REMD [2]; we reported a E,pH,T-REMD simulation in which 576 GPUs were used simultaneously. One of the systems we studied here is the Desulfovibrio vulgaris Hildenborough cytochrome c3, a relatively small protein that contains four heme groups. Each heme is uniquely associated to a different Eo value using a model and experimental data, thus our simulations can aid validating the assignment of the order in which the hemes are reduced. This ordering is of significant biological importance. In here we also report recent implementations that allowed extending our methodologies to the study of Proton-Coupled Electron Transfer (PCET) processes. These processes are important in many biological problems such as respiration, nitrogen fixation, and photosynthesis. These implementations will be part of the future AMBER 20 release. In here we explored PCET processes happening in Tyrosine residues on different systems. We obtain good agreement between our predictions and experimental results.

GPU-accelerated constant pH and redox potential molecular dynamics: Exploring electrochemistry in AMBER

2019 Fall National Meeting

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