       Document 0356
 DOCN  M9610356
 TI    PRO_LIGAND: an approach to de novo molecular design. 4. Application to
       the design of peptides.
 DT    9601
 AU    Frenkel D; Clark DE; Li J; Murray CW; RObson B; Waszkowycz B; Westhead
       DR; Proteus Molecular Design Ltd., Macclesfield, Cheshire, U.K.
 SO    J Comput Aided Mol Des. 1995 Jun;9(3):213-25. Unique Identifier :
       AIDSLINE MED/96044957
 AB    In some instances, peptides can play an important role in the discovery
       of lead compounds. This paper describes the peptide design facility of
       the de novo drug design package, PRO_LIGAND. The package provides a
       unified framework for the design of peptides that are similar or
       complementary to a specified target. The approach uses single amino acid
       residues, selected from preconstructed libraries of different residues
       and conformations, and places them on top of predefined target
       interaction sites. This approach is a well-tested methodology for the
       design of organics but has not been used for peptides before. Peptides
       represent a difficulty because of their great conformational flexibility
       and a study of the advantages and disadvantages of this simple approach
       is an important step in the development of design tools. After a
       description of our general approach, a more detailed discussion of its
       adaptation to peptides is given. The method is then applied to the
       design of peptide-based inhibitors to HIV-1 protease and the design of
       structural mimics of the surface region of lysozyme. The results are
       encouraging and point the way towards further development of interaction
       site-based approaches for peptide design.
 DE    Amino Acid Sequence  Binding Sites  *Drug Design
       Epitopes/CHEMISTRY/GENETICS  HIV Protease/CHEMISTRY  HIV Protease
       Inhibitors/CHEMISTRY  HIV-1/DRUG EFFECTS/ENZYMOLOGY  Models, Molecular
       Molecular Sequence Data  Muramidase/CHEMISTRY/GENETICS/IMMUNOLOGY
       Peptides/*CHEMISTRY  Protein Conformation  *Software  JOURNAL ARTICLE

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

