An immunophysical study of the complement system: Examples for the pH dependence of protein binding and stability

Abstract

We present an immunophysical study for the binding and stability and related properties for selected proteins of the complement system, which is an innate immune defense against invading pathogens. The physical methods we use are based on electrostatic calculations and molecular dynamic simulations. We present applications for the predictions of (1) the titration of complement protein C3d, complement receptor CR2, C3d:CR2 complex, and viral complement inhibitor VCP; (2) the pH dependence of the binding between C3d and CR2; (3) the pH dependence of stability for VCP using molecular dynamics snapshots and (4) the pH dependence of conformational changes for VCP during molecular dynamics. We present critical discussions on the physical origins of the predicted data.