Linked Life Data

9154975

Source:http://linkedlifedata.com/resource/pubmed/id/9154975

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
1997-6-6
pubmed:abstractText
The binding of sulfonamide inhibitors to human thrombin is examined to evaluate the viability of calculating free energies of binding, deltaGb, utilizing Monte Carlo (MC) statistical mechanics with a linear response approach. Coulombic and van der Waals energy components determined from MC simulations of the bound and unbound inhibitors solvated in water plus a solvent-accessible surface area term, as an index for cavity formation, were correlated with the free energies of binding for the inhibitor MD-805 and six derivatives. The best correlations yield an average error of 0.8 kcal/mol for the seven binding affinities, which cover an observed range of 6.0 kcal/mol. The MC simulations also provided insights into the interactions occurring in the active site and the origins of variations in deltaGb. Equatorial placement of the carboxylate group at C2 in the piperidine ring of the inhibitors causes electrostatic destabilization with the side chain of Glu-H192, while axial disposition of the C4-methyl group reduces favorable hydrophobic interactions in the P-pocket of the enzyme.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:day
9
pubmed:volume
40
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1539-49
pubmed:dateRevised
2004-12-8
pubmed:meshHeading
pubmed:year
1997
pubmed:articleTitle
Binding affinities for sulfonamide inhibitors with human thrombin using Monte Carlo simulations with a linear response method.
pubmed:affiliation
Department of Chemistry, Yale University, New Haven, Connecticut 06520-8107, USA.
pubmed:publicationType
Journal Article