Abstract
Mechanosensitive channel of large conductance (MscL) detects and responds to changes in the pressure profile of cellular membranes and transduces the mechanical energy into electrical and/or chemical signals. MscL can be activated using ultrasonic or chemical activation methods to improve the absorption of medicines and bioactive compounds into cells. However, re-engineering chemical signals such as pH change can trigger channel activation in MscL. This study elucidates the activation mechanism of an engineered MscL at an atomic level through a combination of equilibrium and non-equilibrium (NE) molecular dynamics (MD) simulations. Comparing the wild-type (WT) and engineered MscLactivation processes suggests that the two systems are likely associated with different active states and different transition pathways. These findings indicate that (1) periplasmic loops play a key role in the activation process of MscL, (2) the loss of various backbone-backbone hydrogen bonds and salt bridge interactions in the engineered MscLchannel causes the spontaneous opening of the channel, and (3) the most significant interactions lost during the activation process are between the transmembrane helices 1 and 2 in engineered MscLchannel. The orientation-based biasing approach for producing and optimizing an open MscL model used in this work is a promising way to characterize unknown protein functional states and investigate the activation processes in ion channels and transmembrane proteins in general. This work paves the way for a computational framework for engineering more efficient pH-sensing mechanosensitive channels.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
More From: Computational and Structural Biotechnology Journal
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.