Mechanical forces are prevalent in diverse cellular processes, such as cell division, motility, and adhesion. “Mechanoresponsive” proteins and peptides are present which respond to applied forces and change in structure and function to facilitate these cellular processes. Experimental techniques such as single-force spectroscopy have been invaluable in studying protein mechanics, including force-extension curves. Scientists have also developed Tension Sensor Modules which have been used to determine the magnitude and location of forces inside cells. However, these methods are not sufficient to reveal structural changes of peptides under small forces, which is a key detail in studying processes involving mechanosensation. It is also not fully understood why certain amino acid sequences are better suited to sensing tension and what those specific force regimes are and why. Therefore, it becomes imperative to implement computational tools such as Molecular Dynamics (MD) and Enhanced Sampling to better understand force response in peptide tension sensors at the molecular level. We present a novel approach that our group has developed called the Infinite Switch Simulated Tempering in Force (FISST) method, which allows us to determine the effect of a particular force on an MD simulation and uses that force to overcome energetic barriers, within a specified force range. We present scenarios in which the method produces agreeable results and also instances where the method begins to fail and ways to improve the method. Optimizing the method for simpler systems will help us apply the technique to more complicated molecular machines.

Enhanced sampling molecular dynamics to understand for response in peptide tension sensors

ACS Spring 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.