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Title: Computationally exploring the mechanism of bacteriophage T7 gp4 helicase translocating along ssDNA
Bacteriophage T7 gp4 helicase has served as a model system for understanding mechanisms of hexameric replicative helicase translocation. The mechanistic basis of how nucleoside 5′-triphosphate hydrolysis and translocation of gp4 helicase are coupled is not fully resolved. Here, we used a thermodynamically benchmarked coarse-grained protein force field, Associative memory, Water mediated, Structure and Energy Model (AWSEM), with the single-stranded DNA (ssDNA) force field 3SPN.2C to investigate gp4 translocation. We found that the adenosine 5′-triphosphate (ATP) at the subunit interface stabilizes the subunit–subunit interaction and inhibits subunit translocation. Hydrolysis of ATP to adenosine 5′-diphosphate enables the translocation of one subunit, and new ATP binding at the new subunit interface finalizes the subunit translocation. The LoopD2 and the N-terminal primase domain provide transient protein–protein and protein–DNA interactions that facilitate the large-scale subunit movement. The simulations of gp4 helicase both validate our coarse-grained protein–ssDNA force field and elucidate the molecular basis of replicative helicase translocation.  more » « less
Award ID(s):
2019745
NSF-PAR ID:
10416850
Author(s) / Creator(s):
; ; ; ; ; ; ;
Date Published:
Journal Name:
Proceedings of the National Academy of Sciences
Volume:
119
Issue:
32
ISSN:
0027-8424
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
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