The conformational ensemble of an intrinsically disordered protein

Abstract

It is becoming increasingly realized that conformational flexibility, manifested as transitions among multiple states accessible to a macromolecular system, is also of critical importance to function. Many examples now exist of functional assemblies where flexibility is of paramount biological importance including intrinsically disordered proteins and multidomain kinases. Understanding this solution conformational flexibility remains a critical challenge in structural biology. We determined the conformational ensemble of the disordered N terminal of the c-Src kinase by combining small-angle X-ray (SAXS) scattering and molecular dynamics (MD) simulation. To interpret the ensemble averaged structural information obtained by SAXS, we conducted Hamiltonian replica exchange MD (HREXM), which enhance considerably the sampling of configurational states. We calculated theoretical SAXS intensities from the atomic coordinates of the simulations and compared to the experiments. We found that HERMD reproduced, without any fitting, the experimental SAXS intensities. The combined experimental and computational approach provides a detailed physical model of the conformational ensemble of c-Src. Simulation structure of the intrinsically disordered c-Src This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.