Document 0598
 DOCN  M9650598
 TI    Empirical free energy calculations of ligand-protein crystallographic
       complexes. I. Knowledge-based ligand-protein interaction potentials
       applied to the prediction of human immunodeficiency virus 1 protease
       binding affinity.
 DT    9605
 AU    Verkhivker G; Appelt K; Freer ST; Villafranca JE; Agouron
       Pharmaceuticals Inc., San Diego, CA 92121-1121, USA.
 SO    Protein Eng. 1995 Jul;8(7):677-91. Unique Identifier : AIDSLINE
       MED/96156574
 AB    The steadily increasing number of high-resolution human immunodeficiency
       virus (HIV) 1 protease complexes has been the impetus for the
       elaboration of knowledge-based mean field ligand-protein interaction
       potentials. These potentials have been linked with the hydrophobicity
       and conformational entropy scales developed originally to explain
       protein folding and stability. Empirical free energy calculations of a
       diverse set of HIV-1 protease crystallographic complexes have enabled a
       detailed analysis of binding thermodynamics. The thermodynamic
       consequences of conformational changes that HIV-1 protease undergoes
       upon binding to all inhibitors, and a substantial concomitant loss of
       conformational entropy by the part of HIV-1 protease that forms the
       ligand-protein interface, have been examined. The quantitative breakdown
       of the entropy-driven changes occurring during ligand-protein
       association, such as the hydrophobic contribution, the conformational
       entropy term and the entropy loss due to a reduction of rotational and
       translational degrees of freedom, of a system composed to ligand,
       protein and crystallographic water molecules at the ligand-protein
       interface has been carried out. The proposed approach provides
       reasonable estimates of distinctions in binding affinity and gives an
       insight into the nature of enthalpyentropy compensation factors detected
       in the binding process.
 DE    Crystallization  Human  HIV Protease/CHEMISTRY/*METABOLISM  HIV Protease
       Inhibitors/CHEMISTRY  Ligands  Models, Chemical  Oligopeptides/CHEMISTRY
       Protein Binding  Substrate Specificity  Thermodynamics  Water/CHEMISTRY
       JOURNAL ARTICLE

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