Understanding Conformational Changes in Periplasmic Binding Proteins

Abstract

Ligand binding is often accompanied by a conformational change in the protein. Whether this ligand binding precedes or succeeds the conformational change determines the mechanism of ligand recognition (conformational selection (CS) or induced fit (IF)). Despite having similar structures the histidine binding protein (HisJ) binds its ligand through CS while the maltose binding protein (MBP) binds its ligand through the IF mechanism. We simulate and compare the conformational transitions of HisJ and MBP using dual structure-based models and molecular dynamics simulations in order to understand the structural features that enable the different ligand binding mechanisms. Periplasmic binding proteins such as MBP and HisJ have been used in biotechnological applications as ligand sensors and understanding the role of individual structural features in conformational transitions could be used to tune the binding rates of such sensors.