TY - JOUR
T1 - Single-molecule biophysics experiments in silico
T2 - Toward a physical model of a replisome
AU - Maffeo, Christopher
AU - Chou, Han Yi
AU - Aksimentiev, Aleksei
N1 - This work was supported by the grants from the National Science Foundation (PHY-1430124), and the National Institutes of Health (GM137015 and P41-GM104601). The supercomputer time was provided through XSEDE Allocation Grant MCA05S028 and the Leadership Resource Allocation MCB20012 on Frontera of the Texas Advanced Computing Center. A.A. and C.M. thank Taekjip Ha and Yann Chemla for insightful discussions and sharing single molecule data. A.A. and C.M. designed the research. H-Y.C. and C.M. performed the research. C.M. H-Y.C. and A.A. wrote the manuscript. None to declare.
This work was supported by the grants from the National Science Foundation ( PHY-1430124 ), and the National Institutes of Health ( GM137015 and P41-GM104601 ). The supercomputer time was provided through XSEDE Allocation Grant MCA05S028 and the Leadership Resource Allocation MCB20012 on Frontera of the Texas Advanced Computing Center . A.A. and C.M. thank Taekjip Ha and Yann Chemla for insightful discussions and sharing single molecule data.
PY - 2022/5/20
Y1 - 2022/5/20
N2 - 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.
AB - 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.
KW - Biophysical Chemistry
KW - Biophysical chemistry
KW - Biophysics
KW - Physical chemistry
UR - http://www.scopus.com/inward/record.url?scp=85129569194&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85129569194&partnerID=8YFLogxK
U2 - 10.1016/j.isci.2022.104264
DO - 10.1016/j.isci.2022.104264
M3 - Article
C2 - 35521518
AN - SCOPUS:85129569194
SN - 2589-0042
VL - 25
JO - iScience
JF - iScience
IS - 5
M1 - 104264
ER -