Linked Life Data

15789428

Source:http://linkedlifedata.com/resource/pubmed/id/15789428

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2005-4-25
pubmed:abstractText
Full quantum mechanical computational study has been carried out to study binding of efavirenz (EFZ), a second generation FDA approved nonnucleoside inhibitor, to HIV-1 reverse transcriptase (RT) and its K103N and Y181C mutants using the MFCC (molecular fractionation with conjugate caps) method. The binding interaction energies between EFZ and each protein fragment are calculated using a combination of HF/3-21G, B3LYP/6-31G* and MP2/6-31G* ab initio levels. The present computation shows that Efavirenz binds to HIV-1 RT predominantly through strong electrostatic interaction with the Lys101 residue. The small loss of binding to K103N mutant by Efavirenz can be attributed to a slightly weakened attractive interaction between the drug and Lys101 due to a conformational change of mutation. The small loss of binding to Y181C mutant by efavirenz can be attributed to the Glu698 residue moving closer to EFZ due to conformational change, which results in an increase of repulsive energy relative to the wild type (WT). The binding of efavirenz-derived DPC961 to HIV-1 RT is enhanced by an additional attractive interaction to residue Hid235 and reduced repulsion to Glu698, resulting in an increase of binding energy by about 4 kcal/mol.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1097-0134
pubmed:author
pubmed:copyrightInfo
Copyright 2005 Wiley-Liss, Inc.
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
59
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
489-95
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Quantum study of mutational effect in binding of efavirenz to HIV-1 RT.
pubmed:affiliation
Institute of Theoretical and Computational Chemistry, Key Laboratory of Mesoscopic Chemistry, College of Chemistry and Chemical Engineering, Nanjing University, Nanjing, China.
pubmed:publicationType
Journal Article