Journal
PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
Volume 87, Issue 10, Pages 805-814Publisher
WILEY
DOI: 10.1002/prot.25707
Keywords
actin; binding free energy; conformational selection; electrostatic interaction; flexibility; molecular dynamics; myosin; principal component analysis; root mean squared fluctuation; tropomyosin; van der Waals interaction
Categories
Funding
- American Heart Association [14GRNT18980033]
Ask authors/readers for more resources
Tropomyosin (Tpm) is a dimeric coiled-coil protein that binds to filamentous actin, and regulates actin-myosin interaction by moving between three positions corresponding to the blocked, closed, and open states. To elucidate how Tpm undergoes transitions between these functional states, we have built structural models and conducted extensive molecular dynamics simulations of the Tpm-actins/myosin complex in the closed and open states (total simulation time >1.4 mu s). Based on the simulation trajectories, we have analyzed the dynamics and energetics of a truncated Tpm interacting with actins/myosin under the physiological conditions. Our simulations have shown distinct dynamics of four Tpm periods (P3-P6), featuring pronounced biased fluctuations of P4 and P5 toward the open position in the closed state, which is consistent with a conformational selection mechanism for Tpm-regulated myosin binding. Additionally, we have identified key residues of Tpm specifically binding to actins/myosin in the closed and open state. Some of them were validated as functionally important in comparison with past functional/clinical studies, and the rest will make promising targets for future mutational experiments.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available