摘要：SummaryThe interpretation of single-molecule experiments is frequently aided by computational modeling of biomolecular dynamics. The growth of computing power and ongoing validation of computational models suggest that it soon may be possible to replace some experiments outright with computational mimics. Here, we offer a blueprint for performing single-molecule studiesin silicousing a DNA-binding protein as a test bed. We demonstrate how atomistic simulations, typically limited to sub-millisecond durations and zeptoliter volumes, can guide development of a coarse-grained model for use in simulations that mimic single-molecule experiments. We apply the model to recapitulate,in silico, force-extension characterization of protein binding to single-stranded DNA and protein and DNA replacement assays, providing a detailed portrait of the underlying mechanics. Finally, we use the model to simulate the trombone loop of a replication fork, a large complex of proteins and DNA.Graphical abstractDisplay OmittedHighlights•Coarse-grained model derived from all-atom simulation recapitulates experiments•Model reproduces the elastic response to force and exchange dynamics•Model reveals structure of intermediate states usually inaccessible to experiment•Model applied to viral replisome with trombone loop containing tens of SSB proteinsPhysical chemistry; Biophysical chemistry; Biophysics; Biophysical Chemistry
