We propose a strategy to simulate the dynamics of molecular assemblies over long times, provided they have a hierarchical and modular nature. In the scheme, fast fluctuations are averaged into a set of effective potentials (fluctuation softened potentials or FSPs), and the remaining slower dynamics are propagated in a drastically reduced configuration space (coupled energy landscapes or CEL). As a preliminary validation of the FSPs we compute the free energy of binding of a protein complex (RNase:barstar) for different relative positionings of the proteins. As a demonstration of CEL, we simulate the dynamics of microtubule unraveling upon hydrolysis of bound nucleotides. The method should allow the use of time steps hundreds to thousands of times longer than in conventional molecular dynamics, so that with only atomic structures and interactions as input, motions over human time scales (>ms) could be simulated.
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Su, J.T. A Strategy to Simulate the Dynamics of Molecular Assemblies Over Long Times. MRS Online Proceedings Library 1274, 602 (2010). https://doi.org/10.1557/PROC-1274-QQ06-02