Coarse-grained simulations have emerged as invaluable tools for studying conformational changes in biomolecules. To evaluate the effectiveness of computationally inexpensive coarse-grained models in studying global and local dynamics of large protein systems like aminoacyl-tRNA synthetases, we have performed coarse-grained normal mode analysis, as well as principle component analysis on trajectories of all-atom and coarse-grained molecular dynamics simulations for three aminoacyl-tRNA synthetases—Escherichia coli methionyl-tRNA synthetase, Thermus thermophilus leucyl-tRNA synthetase, and Enterococcus faecium prolyl-tRNA synthetase. In the present study, comparison of predicted dynamics based on B-factor and overlap calculations revealed that coarse-grained methods are comparable to the all-atom simulations in depicting the intrinsic global dynamics of the three enzymes. However, the principal component analyses of the motions obtained from the all-atom molecular dynamics simulations provide a superior description of the local fluctuations of these enzymes. In particular, the all-atom model was able to capture the functionally relevant substrate-induced dynamical changes in prolyl-tRNA synthetase. The alteration in the coupled dynamics between the catalytically important proline-binding loop and its neighboring structural elements due to substrate binding has been characterized and reported for the first time. Taken together, the study portrays comparable and contrasting situations in studying the functional dynamics of large multi-domain aminoacyl-tRNA synthetases using coarse-grained and all-atom simulation methods.
Written by Sudeep Bhattacharyay and Sanchita Hati
In This Story
- Alexander Strom
- Samuel Fehling
Departments + Programs
You may also like:
Faculty mentors change lives
Amelia Montie credits a team of faculty mentors for helping her thrive at UW-Eau Claire, including during her final semester of college as she is managing a new diagnosis of Type 1 diabetes as well as a global pandemic that moved all classes online.
Building connections, embracing opportunities
As Monica Dickson prepares to graduate this spring with a major in biology and a minor in chemistry, she says UW-Eau Claire’s supportive campus community is a big part of the reason she can pursue her dream of becoming a veterinarian.
Capturing COVID-19 stories, artifacts
Students in Dr. Cheryl Jiménez Frei’s public history class are helping to shape how future generations will understand COVID-19 and its impact on the region by capturing oral histories and artifacts from people in the Chippewa Valley.