Article

Determining the structural basis for specificity of ligands using crystallographic screening.

Faculdade de Biociências-PUCRS, Porto Alegre-RS, 90619-900, Brazil.
Cell Biochemistry and Biophysics (impact factor: 3.74). 02/2006; 44(3):405-11. DOI:10.1385/CBB:44:3:405 pp.405-11
Source: PubMed

ABSTRACT Crystallographic screening has been used to identify new inhibitors for potential target for drug development. Here, we describe the application of the crystallographic screening to assess the structural basis of specificity of ligands against a protein target. The method is efficient and results in detailed crystallographic information. The utility of the method is demonstrated in the study of the structural basis for specificity of ligands for human purine nucleoside phosphorylase (PNP). Purine nucleoside phosphorylase catalyzes the phosphorolysis of the N-ribosidic bonds of purine nucleosides and deoxynucleosides. This enzyme is a target for inhibitor development aiming at T-cell immune response modulation and has been submitted to extensive structure- based drug design. This methodology may help in the future development of a new generation of PNP inhibitors.

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    Article: MolDock applied to structure-based virtual screening.
    Walter Filgueira De Azevedo
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    ABSTRACT: Molecular docking is a simulation process where the binding of a small molecule is identified in the structure of a protein target. There are several different computational approaches to solve this problem. Here it will be described recent developments in application of evolutionary algorithms to molecular docking simulations. Evolutionary algorithms are classified as a group of computational techniques based on the concepts of Darwin's theory of evolution that are designed to the best possible find solution to optimisation problems. A successfully implementation of this algorithm can be found in the program MolDock. The main features of MolDock are reviewed here we also describe application of MolDock to purine nucleoside phosphorylase, shikimate kinase and cyclin-dependent kinase 2.
    Current drug targets 03/2010; 11(3):327-34. · 3.93 Impact Factor
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Keywords

crystallographic information
 
crystallographic screening
 
deoxynucleosides
 
drug design
 
extensive structure-
 
human purine nucleoside phosphorylase
 
inhibitor development
 
ligands
 
N-ribosidic bonds
 
new generation
 
new inhibitors
 
PNP
 
PNP inhibitors
 
potential target
 
protein target
 
purine nucleosides
 
specificity
 
structural basis
 
T-cell immune response modulation