Protein structural transitions couple with fluctuations of the aqueous environment to enable biological function. Although decades of experiment have investigated protein-motion hydration couplings, atomistic details regarding global hydration structures and their transitions associated with large-scale protein functional motions have remained elusive. Molecular dynamics (MD) simulations are well-suited for studying protein-hydration couplings as they provide excellent spatial and temporal resolution to observe functional dynamics. Unfortunately, sampling long-timescale motions by MD simulation is challenging even when utilizing state-of-the-art computing resources. The Orthogonal Space Tempering (OST) enhanced sampling MD technique was designed to access long timescales by simultaneously accelerating fluctuations of a targeted dynamic and that of its coupled environment. Here, the OST method is utilized to study protein and water conformational transitions of the TEM-1 Beta-lactamase enzyme which harbors several water molecules critical for the cleavage of antibiotic substrates. Conformational transitions of TEM-1 and the aqueous environment are investigated with a novel analysis toolkit designed to reveal couplings among protein and water collective motions.

Protein-motion coupled hydration structure and dynamics

2019 Spring National Meeting

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