|Physical-Organic Approaches to Studying Protein Chemistry|
: 64 : 2017.09.20 12:56
|일시 : 2017.09.20 17:00|
|소속 : 경희대학교 응용화학과|
|발표자 : 강경태|
|장소 : RA204|
Biomolecular recognition is governed as much by rearrangements of the water that hydrates the interacting molecules as it is governed by their direct interactions. A detailed understanding of the mechanisms by which these rearrangements contribute to the thermodynamics of recognition processes is, thus, essential for better understanding—and predicting—the energetics of important biomolecular recognitions.
In this respect, the hydrophobic effect—the tendency of nonpolar surfaces to associate in aqueous solution—is one of the major driving forces of many biomolecular recognition events. The hydrophobic effect arises from free energetically favorable rearrangements of water, whose thermodynamic consequences are fairly well understood for flat, nonpolar entities in aqueous solution (where the intermolecular association of such entities gives rise to the entropically favorable, enthalpically unfavorable release of ordered waters from their surfaces), but incompletely understood—and difficult to predict—for interactions between ligands and the morphologically complex and chemically heterogeneous binding pockets of proteins.
In this talk, I will introduce our efforts to examine the role of water filling the binding pocket of human carbonic anhydrase II (HCAII, EC 4.2.11) in its bindings with structurally varied sulfonamide ligands, by combining isothermal titration calorimetry, X-ray crystallography, site-directed mutagenesis, and molecular dynamics simulations. By this set of methods, we showed that (i) the hydrophobic surface area of a ligand does not improve DGºb, unless that increased non-polar area is buried in the binding process, and values of DHºb and -TDSºb depend on the structure (or morphology) of a ligand; (ii) reorganizing networks of water inside the binding pocket by mutating amino acids thereof brings about huge and compensating changes in values of DHºband -TDSºb.