Linked Life Data

10450088

Source:http://linkedlifedata.com/resource/pubmed/id/10450088

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
1999-9-23
pubmed:abstractText
A structure-based ligand design method is proposed and tested. The method is based on stochastic dynamics simulation of multiple copies of molecular building blocks in the presence of a receptor molecule. The molecular building blocks are assembled into candidate compounds "on the fly" at given intervals during the simulation. In the algorithm, a special effort is made to explore different possible combinations of building blocks and to select an optimum combination. By repeating the cycle of deconstruction and reconstruction in a single simulation, a set of candidate compounds that can be built from the building blocks evolves and is dynamically optimized. The method was tested by breaking two known flexible human immunodeficiency virus type 1 protease inhibitors into building blocks and reassembling them in the active site of the enzyme. For the inhibitor L700417, a set of conformations was generated by the calculation. Among these, the original compound was recovered with the lowest energy at the experimentally observed binding site and in the correct conformation. For pepstatin, the experimentally observed binding mode of the backbone of the inhibitor was reproduced by a calculation in which the building blocks corresponding to the side-chain groups were omitted. Proteins 1999;36:462-470.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0887-3585
pubmed:author
pubmed:copyrightInfo
Copyright 1999 Wiley-Liss, Inc.
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
36
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
462-70
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
Structure-based ligand design by dynamically assembling molecular building blocks at binding site.
pubmed:affiliation
Laboratory of Structural Biology, University of Science and Technology of China (USTC), Chinese Academy of Science, and School of Life Science, USTC, Hefei, Anhui, China. haiyan@chem.duke.edu
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't