title: Contribution of translational and rotational motions to molecular association in aqueous solution.
abstract: Much uncertainty and controversy exist regarding the estimation of the enthalpy, entropy, and free energy of overall translational and rotational motions of solute molecules in aqueous solutions, quantities that are crucial to the understanding of molecular association/recognition processes and structure-based drug design. A critique of the literature on this topic is given that leads to a classification of the various views. The major stumbling block to experimentally determining the translational/rotational enthalpy and entropy is the elimination of vibrational perturbations from the measured effects. A solution to this problem, based on a combination of energy equi-partition and enthalpy-entropy compensation, is proposed and subjected to verification. This method is then applied to analyze experimental data on the dissociation/unfolding of dimeric proteins. For one translational/rotational unit at 1 M standard state in aqueous solution, the results for enthalpy (H degrees (tr)), entropy (S degrees (tr)), and free energy (G degrees (tr)) are H (degrees) (tr) = 4.5 +/- 1.5RT, S (degrees) (tr) = 5 +/- 4R, and G (degrees) (tr) = 0 +/- 5RT. Therefore, the overall translational and rotational motions make negligible contribution to binding affinity (free energy) in aqueous solutions at 1 M standard state.
authors.affiliation: Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, Utah 84112, USA. yby1@utah.edu
authors.forename: Y B
authors.initials: YB
authors.lastname: Yu
authors.forename: P L
authors.initials: PL
authors.lastname: Privalov
authors.forename: R S
authors.initials: RS
authors.lastname: Hodges
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism*; D002152:Calorimetry, Differential Scanning; D019281:Dimerization; D004735:Energy Transfer; D019277:Entropy; D006863:Hydrogen-Ion Concentration; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D011489:Protein Denaturation; D017510:Protein Folding; D015203:Reproducibility of Results; D012399:Rotation; D012996:Solutions / Q000737:chemistry* / Q000378:metabolism; D012997:Solvents / Q000737:chemistry / Q000378:metabolism; D013816:Thermodynamics; D014732:Vibration; D014867:Water / Q000737:chemistry / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D010455:Peptides; D012996:Solutions; D012997:Solvents; C018150:subtilisin inhibitor protein, Streptomyces; D014867:Water