title: A multidisciplinary approach to probing enthalpy-entropy compensation and the interfacial mobility model.
abstract: In recent years, interfacial mobility has gained popularity as a model with which to rationalize both affinity in ligand binding and the often observed phenomenon of enthalpy-entropy compensation. While protein contraction and reduced mobility, as demonstrated by computational and NMR techniques respectively, have been correlated to entropies of binding for a variety of systems, to our knowledge, Raman difference spectroscopy has never been included in these analyses. Here, nonresonance Raman difference spectroscopy, isothermal titration calorimetry, and X-ray crystallography were utilized to correlate protein contraction, as demonstrated by an increase in protein interior packing and decreased residual protein movement, with trends of enthalpy-entropy compensation. These results are in accord with the interfacial mobility model and lend additional credence to this view of protein activity.
authors.affiliation: Department of Chemistry, Duke University, Durham, North Carolina 27708, USA.
authors.forename: Erin M
authors.initials: EM
authors.lastname: Wilfong
authors.forename: Yuri
authors.initials: Y
authors.lastname: Kogiso
authors.forename: Sivaramakrishnan
authors.initials: S
authors.lastname: Muthukrishnan
authors.forename: Thomas
authors.initials: T
authors.lastname: Kowatz
authors.forename: Yu
authors.initials: Y
authors.lastname: Du
authors.forename: Amber
authors.initials: A
authors.lastname: Bowie
authors.forename: James H
authors.initials: JH
authors.lastname: Naismith
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Hadad
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Toone
authors.forename: Terry L
authors.initials: TL
authors.lastname: Gustafson
mesh_terms: D001665:Binding Sites; D019295:Computational Biology; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D006877:Hydroxamic Acids / Q000737:chemistry*; D008024:Ligands; D019278:Matrix Metalloproteinase 3 / Q000737:chemistry* / Q000302:isolation & purification; D008958:Models, Molecular; D015394:Molecular Structure; D013059:Spectrum Analysis, Raman; D013237:Stereoisomerism; D013816:Thermodynamics
chemical_list: D006877:Hydroxamic Acids; D008024:Ligands; C115088:CGS 27023; D019278:Matrix Metalloproteinase 3