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Simulations reveal structural mechanism of molecular switch in DNA repair protein

10/4/2018 10:29:45 AM CPLC Staff

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Molecular machines play many essential roles in the cell, such asmaintaining the genome. Characterizing the atomistic-level mechanism for thesecomplex machines, though challenging, is crucial to link protein structure withRPPR function. Previously, single-molecule experiments by the Ha and Chemla groups demonstrated that the DNA repair helicase UvrD can switch its activity dramaticallyby changing the conformation of its regulatory 2B subdomain (Comstock et al., Science, 2015). However, the structural basis and driver for this functional switchremained unclear. CPLC postdoc Wen Ma from the Schulten group, in collaboration with Luthey-Schulten and Chemla, employed a novel computational approach to study the molecular mechanism of this functional switch, integrating enhanced sampling MD simulations with bioinformatics tools that survey structural information from homologs. The simulations predicted a new molecular structure responsible for one of UvrD’s functions, as well as an important metastable state that plays a crucialrole in switching the helicase’s function. In addition, simulation results were validated by comparing simulated FRET efficiency distributions for the predicted structures withthe experimental measurements, showing excellent agreement. Finally, a physical model combining the free-energy simulation results and the measured equilibrium constant from experiments explains how UvrD-like helicases switch function. Referto: Ma et al. eLife (2018).


The College of Engineering at the University of Illinois at Urbana-Champaign received a record 10,686 applications for the fall 2014 freshmen class—a 19 percent increase from last year’s applicant pool of 8,954 students. The number of applicants has doubled since 2010, when 5,330 students applied.

At the same time, the quality of the applicant pool has never been higher. The average composite ACT score for entering classes rose from 31.2 in 2010 to 32.1 in 2013. The average composite ACT score for applicants has risen from 30.4 in 2010 to 30.9 for this year’s applicants.

Illinois’ engineering program is consistently ranked in the Top 5 nationally and internationally, and it is among the country’s Top 3 schools in terms of the number of undergraduate degrees awarded each year.

“This major expansion in the number of applicants is a great vote of confidence,” said Andreas Cangellaris, dean of the College of Engineering. “It tells us that people recognize the value of an engineering degree from Illinois. And it tells us that students appreciate that Illinois’ comprehensive range of majors and innovative ways of teaching allow them to specialize while developing into a well-rounded engineer.”

To keep pace with this growing demand, the College of Engineering at Illinois has expanded its faculty, with a net increase of 23 new faculty members since 2010, with plans to add another 40 to 50 faculty over the next five years.