Over the past several years we have developed a novel approach to including pH in molecular dynamics simulations called CpHMD (Constant pH Molecular Dynamics). We have developed a hierarchy of models that include both implicit and explicit solvent frameworks to carry out molecular dynamics under conditions of constant pH and salt concentrations. In this talk I will focus on applications of these approaches to the de novo engineering of the protein-protein interface in the small dimeric protein HdeA, which is a significant protein in enteric bacteria such as E. Coli and operates through a pH sensing function as a pH stress induced chaperone. In this system we identified the key pH sensing residues and through site directed mutagenesis studies, in collaboration with the James Bardwell and Linda Foit, we developed a constitutively active chaperone function into this system. An overview of our developments in this problem as well as exploration of other pH-mediated processes in biology will be described.

Engineering electrostatic control of protein-protein interfaces and chaperone activity

246th National Meeting (2013)

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