We introduce a variational approximation to the microscopic dynamics of rare conformational transitions of macromolecules. We show that within this framework it is possible to simulate on a small computer cluster conformational reactions as complex as protein folding, using state-of-the-art all-atom force fields in explicit solvent. The same approach also yields the potential of mean-force for reaction coordinates, the reaction rate and transition path time. For illustration and validation purposes, we test this method against the results of protein folding MDsimulations which were obtained on the Anton supercomputer, using the same all-atom force field  . We find that our approach yields consistent results at a computational cost which is many orders of magnitude smaller than that required by standard MD simulations .
We introduce a variational approximation to the microscopic dynamics of rare conformational transitions of macromolecules. Within this framework it is possible to simulate on a small computer cluster reactions as complex as protein folding, using state of the art all-atom force fields in explicit solvent. We test this method against molecular dynamics (MD) simulations of the folding of an alpha- and a beta-protein performed with the same all-atom force field on the Anton supercomputer . We find that our approach yields results consistent with those of MD simulations, at a computational cost orders of magnitude smaller .
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conformational
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state-of-the-art
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The same approach also yields the potential of mean-force for reaction coordinates, the reaction rate and transition path time. For illustration and validation purposes, we
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the results of protein folding MDsimulations which were obtained on the Anton supercomputer, using
molecular dynamics (MD) simulations of the folding of an alpha- and a beta-protein performed with
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on the Anton supercomputer
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consistent results
results consistent with those of MD simulations,
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which is many
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than that required by standard MD simulations