Paper Info
Title
The computer program LUDI: A new method for the de novo design of enzyme inhibitors
Abstract
A new computer program is described, which positions small molecules into clefts of protein structures (e.g. an active site of an enzyme) in such a way that hydrogen bonds can be formed with the enzyme and hydrophobic pockets are filled with hydrophobic groups. The program works in three steps. First it calculates interaction sites, which are discrete positions in space suitable to form hydrogen bonds or to fill a hydrophobic pocket. The interaction sites are derived from distributions of nonbonded contacts generated by a search through the Cambridge Structural Database. An alternative route to generate the interaction sites is the use of rules. The second step is the fit of molecular fragments onto the interaction sites. Currently we use a library of 600 fragments for the fitting. The final step in the present program is the connection of some or all of the fitted fragments to a single molecule. This is done by bridge fragments. Applications are presented for the crystal packing of benzoic acid and the enzymes dihydrofolate reductase and trypsin.
Year
DOI
Venue
1992
10.1007/BF00124387
Journal of computer-aided molecular design
Keywords
Field
DocType
Enzymes,Enzyme inhibitors,Molecular modeling,Drug design,De novo design
Dihydrofolate reductase,Crystallography,Binding site,Molecule,Chemistry,Small molecule,Stereochemistry,Active site,Hydrogen bond,Molecular model,Protein structure
Journal
Volume
Issue
ISSN
6
1
0920-654X
Citations 
PageRank 
References 
74
18.98
2
Authors
1
Name
Order
Citations
PageRank
Hans-joachim Böhm126754.47