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Titolo:
MOLECULAR-DYNAMICS SIMULATIONS OF ADIPOCYTE LIPID-BINDING PROTEIN - EFFECT OF ELECTROSTATICS AND ACYL-CHAIN UNSATURATION
Autore:
RICH MR; EVANS JS;
Indirizzi:
NYU,DEPT BIOL,WASHINGTON SQ NEW YORK NY 10003 NYU,DEPT CHEM NEW YORK NY 10003
Titolo Testata:
Biochemistry
fascicolo: 5, volume: 35, anno: 1996,
pagine: 1506 - 1515
SICI:
0006-2960(1996)35:5<1506:MSOALP>2.0.ZU;2-7
Fonte:
ISI
Lingua:
ENG
Soggetto:
HYDROGEN-BONDED CRYSTALS; NEUTRON-DIFFRACTION DATA; CONSISTENT FORCE-FIELD; FATTY-ACIDS; CONFORMATIONAL DISORDER; JOINT REFINEMENT; 2ND MESSENGER; X-RAY; BILAYER; SPECTROSCOPY;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
44
Recensione:
Indirizzi per estratti:
Citazione:
M.R. Rich e J.S. Evans, "MOLECULAR-DYNAMICS SIMULATIONS OF ADIPOCYTE LIPID-BINDING PROTEIN - EFFECT OF ELECTROSTATICS AND ACYL-CHAIN UNSATURATION", Biochemistry, 35(5), 1996, pp. 1506-1515

Abstract

Molecular dynamics (MD) simulations have been performed on adipocyte lipid-binding protein, using the apo and hole forms, bound with stearic and oleic acid. The contribution of electrostatics to protein dynamics and ligand stabilization was assayed by perturbing the electrostatic charge of Argl06 and Arg126 (positive --> neutral) and the fatty acid (132H) headgroup (negative --> neutral), MD simulations for charged hole forms demonstrated significantly greater electrostatic binding energy and a more stabilized hydrogen bond network than simulations performed using neutral forms. Electrostatics, however, appeared to have little effect on fatty acid behavior, e.g., fluctuation of the dihedralhead group; number of dihedral transitions within the acyl chain; andchange in the end-to-end distance for fatty acid. Instead, fatty acidbehavior appeared to be dictated by the presence or absence of an unsaturated bond within the acyl chain, A significantly greater number oftransitions were observed during MD simulations in oleic than stearicacid, In addition, significantly greater fluctuation was observed foroleic acid, within the C2 headgroup and C9 and C11 dihedrals (which lie adjacent to the olefin bond of oleic acid). The dynamic behavior ofthe acyl chain may thereby be more a property of van der Waals contact, and the degree of acyl chain unsaturation, than a function of electrostatics. In the absence of fatty acid, an increase in distance between guanidino carbon centered atoms of Arg126 and Argl06 was observed during MD simulations of the charged apo form. This effect not observedwith the neutral apo form or in any of the hole complexes and, presumbably, was a result of repulsion between the negatively charged arginine sidechains, Conserved waters reflected substantially lower mean-square displacement (msd) in all simulations, except the neutral apo form. This suggests that the presence of either charged amino acids or lipid provides increased order for water within the binding pocket. Theseresults provide a dynamic perspective of the interactive nature within the FABP binding pocket regulated in a complex manner by the electrostatics within the binding cavity, acyl chain structure and behavior, and water energetics.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 24/09/20 alle ore 05:21:33