PNNL

Abstract

The Molecular Dynamics technique Collective variable hyperdynamics (CVHD) interfaced with density functional tight-binding at the GFN1-xTB and GFN2-xTB levels of electronic structure theory has been applied to the H+GAG positively charged peptide system to explore the fragmentation of this simple tripeptide under relatively low temperature/energy conditions. Unlike conventional chemical dynamics simulations which can only be performed up to hundreds of picoseconds when coupled with semi-empirical Hamiltonians, CVHD is able to capture the long-time dynamics of multiple proton hopping, the formation of reversible ring structures, and ester rearrangement of the H+GAG system prior to fragmentation. The CVHD method applied to H+GAG is also able to uncover alternative fragmentation pathways not considered previously such as glycine fragmentation on the N-terminal side of the charged peptide and new cyclic cationic species. These findings in the H+GAG case have implications for other peptide systems.