Protein functional motions, such as enzyme catalysis and biologically-relevant protein conformational change, largely occur on long timescales (microsecond or greater). All-atom molecular dynamics (MD) simulations are ideal for studying the motions of proteins, as they allow for atomic-level visualization and analysis of their structural and dynamical changes. However, all MD simulations face the “timescale problem,” in which long-timescale dynamics cannot be accessed with commonly tractable computing power. The orthogonal space tempering (OST) method was developed to address the timescale problem by simultaneously accelerating both a chosen target perturbation and that of its strongly and weakly coupled environment. Here, we use the OST method to study the protein and water dynamics of myoglobin and L99A T4 lysozyme, both of which have long-timescale conformational changes that have been well-characterized experimentally. These OST simulations revealed large protein conformational changes for both systems consistent with long-timescale structural changes observed in previous experimental studies. Moreover, this work offers novel, atomic-level insight into long-timescale motions of myoglobin and L99A T4 lysozyme.

Simulation study of long-timescale protein dynamics

255th National Meeting (2018)

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