How far the in-silico computing meets real experiments? A study on the structure and dynamics of spin labeled vinculin tail protein by MD simulations and EPR spectroscopy

Abstract

Investigation of conformational changes in a protein is a prerequisite to understand its biological function. To explore these conformational changes in proteins we developed a strategy with the combination of molecular dynamics (MD) simulations and electron paramagnetic resonance (EPR) spectroscopy. Vinculin tail protein is chosen as a model system as conformational changes within the vinculin protein are believed to be important for its biological function at the sites of cell adhesion. The calculated EPR spectra from the MD simulations trajectories of selected spin labeled positions are comparable to the experimental EPR spectra. To estimate the magnitude of helix displacements in the vinculin tail domain, direct distance measurements between pairs of spin label side chains were performed. The MD simulations results in combination with EPR data show that the changes in spin label mobility in vinculin tail provide a powerful means of mapping protein folds and their conformational changes.