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Titolo:
Conformational analysis of the HIV-1 virus reverse transcriptase nonnucleoside inhibitors: TIBO and nevirapine
Autore:
Abrahao, O; Nascimento, PBD; Galembeck, SE;
Indirizzi:
Univ Sao Paulo, Fac Filosofia Ciencias & Letras Ribeirao Preto, Dept Quim,Lab Modelagem Mol, BR-14040901 Ribeirao Preto, SP, Brazil Univ Sao Paulo Ribeirao Preto SP Brazil BR-14040901 BCo Preto, SP, Brazil
Titolo Testata:
JOURNAL OF COMPUTATIONAL CHEMISTRY
fascicolo: 15, volume: 22, anno: 2001,
pagine: 1817 - 1829
SICI:
0192-8651(20011130)22:15<1817:CAOTHV>2.0.ZU;2-C
Fonte:
ISI
Lingua:
ENG
Soggetto:
FORCE-FIELD PARAMETRIZATION; MOLECULAR-ORBITAL METHODS; GAUSSIAN-TYPE BASIS; ORGANIC-MOLECULES; CRYSTAL-STRUCTURE; DRUG-RESISTANCE; PARAMETERS; NNRTIS; IDENTIFICATION; SIMULATIONS;
Keywords:
molecular mechanics parameterization; AMBER; puckering parameters; clustering; Cremer-Pople parameters;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Physical, Chemical & Earth Sciences
Citazioni:
55
Recensione:
Indirizzi per estratti:
Indirizzo: Galembeck, SE Univ Sao Paulo, Fac Filosofia Ciencias & Letras Ribeirao Preto, Dept Quim,Lab Modelagem Mol, Ave Bandeirantes 3900, BR-14040901 Ribeirao Preto, SP, Brazil Univ Sao Paulo Ave Bandeirantes 3900 Ribeirao Preto SP Brazil BR-14040901 BC
Citazione:
O. Abrahao et al., "Conformational analysis of the HIV-1 virus reverse transcriptase nonnucleoside inhibitors: TIBO and nevirapine", J COMPUT CH, 22(15), 2001, pp. 1817-1829

Abstract

TIBO (Tetrahydro-imidazo[4,5,1-jk][1,4]-benzodiazepin-2-one) and nevirapine (11-cyclopropyl-5,11-dihydro-4-methyl-6H-dipyrido[3,2-b:2,3'-e] [1,4]diazepin-6-one) are models for two classes of nonnucleoside inhibitors of the HIV-1 virus reverse transcriptase (NNRTI). This work presents the parameterization of compounds belonging to these two classes in the Cornell et al. force field through ab initio and semiempirical methods. The new parameters were used in the conformational analysis for TIBO R82913, TIBO R79882, and nevirapine. Various conformational search protocols were tested and the pseudosystematic method SUMM led to the best results. A better understanding ofthe distribution of conformers was obtained through clustering techniques in the data reduction stages. It was possible to reproduce various experimental data such as the crystallographic structures of the isolated or reverse transcriptase-complexed (RT) molecules. The proton-proton coupling constants (J(HH)(3)) obtained for TIBO through NMR were also reproduced. Cremer and Pople puckering parameters enabled a precise description of both the conformation of the seven-membered rings and the relative position of the substituents on them. These parameters also demonstrated the efficiency and precision of the two-stage clustering method. (C) 2001 John Wiley & Sons, Inc.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 30/09/20 alle ore 09:18:32