WFU Joint Physics and Chemistry Colloquium

TITLE: Capturing pH mediated physics and chemistry in biological physics

SPEAKER: Professor Charles L. Brooks III,

TIME: Wednesday January 30, 2013 at 4:00 PM

PLACE: Room 101 Olin Physical Laboratory

During the past several years we have established novel methods of molecular dynamics that permit the direct coupling between conformational fluctuations and ionization equilibria in proteins and nucleic acids. These methods, called Constant pH Molecular Dynamics, CpHMD, provide a means of exploring the vast number of pH-mediated processes occurring in biology. In this talk we will focus on recent calculations that explore the role of pH and protein environment in modulating protein function and ionization state of key residues. We will discuss studies that provide basic benchmarks for the approach and compare with experimental pKa values in both "normal" protein systems as well as those from buried charge groups, as studied experimentally by Garcia-Moreno and co-workers recently. We will illustrate the application of CpHMD to elucidate the pH sensing mechanisms in the small bacterial chaperone protein HdeA, where drops in pH trigger protein dissociation and chaperone activity, while relaxation of the pH toward normal cellular levels facilitates substrate release. Extensions of these methods to address pH mediated processes in nucleic acids will be described with exemplary applications to RNA and DNA systems.