Evidence for an electrostatic mechanism of force generation by the bacteriophage T4 DNA packaging motor.
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How viral packaging motors generate enormous forces to translocate DNA into viral capsids remains unknown. Recent structural studies of the bacteriophage T4 packaging motor have led to a proposed mechanism wherein the gp17 motor protein translocates DNA by transitioning between extended and compact states, orchestrated by electrostatic interactions between complimentarily charged residues across the interface between the N- and C-terminal subdomains. Here we show that site-directed alterations in these residues cause force dependent impairments of motor function including lower translocation velocity, lower stall force and higher frequency of pauses and slips. We further show that the measured impairments correlate with computed changes in free-energy differences between the two states. These findings support the proposed structural mechanism and further suggest an energy landscape model of motor activity that couples the free-energy profile of motor conformational states with that of the ATP hydrolysis cycle.
Molecular Dynamics Simulation
Molecular Motor Proteins
Published Version (Please cite this version)10.1038/ncomms5173
Publication InfoMigliori, AD; Keller, N; Alam, TI; Mahalingam, M; Rao, VB; Arya, Gaurav; & Smith, DE (2014). Evidence for an electrostatic mechanism of force generation by the bacteriophage T4 DNA packaging motor. Nat Commun, 5. pp. 4173. 10.1038/ncomms5173. Retrieved from https://hdl.handle.net/10161/15624.
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Associate Professor of Mechanical Engineering and Materials Science
My research laboratory uses physics-based computational tools to provide fundamental, molecular-level understanding of a diverse range of biological and soft-material systems, with the aim of discovering new phenomena and developing new technologies. The methods we use or develop are largely based on statistical mechanics, molecular modeling and simulations, stochastic dynamics, coarse-graining, bioinformatics, machine learning, and polymer/colloidal physics. Our current resear