Single-molecule biophysics experiments in silico: Toward a physical model of a replisome

Christopher Maffeo, Han Yi Chou, Aleksei Aksimentiev

Research output: Contribution to journalArticlepeer-review


The 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 studies in silico using 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.

Original languageEnglish (US)
Article number104264
Issue number5
StatePublished - May 20 2022


  • Biophysical Chemistry
  • Biophysical chemistry
  • Biophysics
  • Physical chemistry

ASJC Scopus subject areas

  • General


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