Document 0514
 DOCN  M9480514
 TI    The effect of physical organic properties on hydrophobic fields.
 DT    9410
 AU    Abraham DJ; Kellogg GE; Department of Medicinal Chemistry, Medical
       College of Virginia,; Virginia Commonwealth University, Richmond
       23298-0540.
 SO    J Comput Aided Mol Des. 1994 Feb;8(1):41-9. Unique Identifier : AIDSLINE
       MED/94308823
 AB    Physical organic structural properties of small molecules and
       macromolecules such as bond count, branching and proximity between
       multiple polar fragments contribute significantly to measured
       hydrophobicity (log P). These structural properties are encoded in the
       Rekker and Leo methods of calculating log P as structural-dependent
       factors. Regardless of the size of the atom primitive set, methods
       predicting log P with only atom primitives can miss subtle structural
       detail within series of related compounds. The HINT (Hydropathic
       INTeractions) model for inter- and intramolecular noncovalent
       interactions calculates atom-based hydrophobic constants, but uses all
       Leo-type factors in the calculation rather than a large set of atom
       primitives. Two types of applications of HINT are discussed: evaluation
       of the binding of an inhibitor (A74704) to HIV-1 protease, where it is
       shown that modeling of the protonation state (i.e., Asp25, Asp125) in
       the protein can strongly influence perceived substrate binding; and the
       use of HINT to calculate a third (hydropathic) field for CoMFA can yield
       a statistically enhanced and predictive model for molecular design.
 DE    *Chemistry, Physical  *Computer Simulation  Hydrogen Bonding  HIV
       Protease/METABOLISM  HIV Protease Inhibitors/METABOLISM  *Models,
       Molecular  *Molecular Structure  Protein Binding  Software  Sugar
       Alcohols/METABOLISM  Valine/ANALOGS & DERIVATIVES/METABOLISM  Water
       JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).