Abstract
Vinculin family (VF) proteins are involved in cell adhesion protein complex. In addition, it is supposed that forces exerted on the adhesion complex are sensed and converted into chemical signals by VF proteins. This mechanosening function can be based on force-induced conformational changes of VF proteins, especially, conformational changes of alpha-helix bundles, the common motif of VF proteins, play an important role on the mechanosensing function. To investigate force-induced conformational changes of proteins in an atomistic scale, steered molecular dynamics (SMD) simulations have been performed as a computational microscope. However, SMD is limited to obtain submicron second time-scale dynamics because of calculating very massive degrees of freedoms of atoms. Therefore, to complete the protein conformational change within a certain time scale, applying forces employed in SMD simulations are usually much higher than those in vivo. This overlarge force often induces unnatural conformational changes. Although these limitations would be resolved by future high-performance computers, biological scientific demands in seeing how proteins are deformed by forces are increased rapidly and become an urgent issue in mechanobiology. Thus, in this study, we investigate conditions of SMD simulations for alpha-helix bundles to avoid unnatural conformational changes as much as possible even in a short time scale. Examining several conditions about locations of points of application of forces, we found that one condition reproduces a desirable conformational change of the helix bundles, while the steric structure of each helix was maintained to be the alpha helix.
