http://www.cnr.it/ontology/cnr/individuo/prodotto/ID1916

HIV-1 protease substrate binding and product release pathways explored with coarse-grained molecular dynamics (Articolo in rivista)

Type

Label

HIV-1 protease substrate binding and product release pathways explored with coarse-grained molecular dynamics (Articolo in rivista) (literal)

Anno

Alternative label

Trylska, J; Tozzini, V; Chang, CA; McCammon, JA (2007)
HIV-1 protease substrate binding and product release pathways explored with coarse-grained molecular dynamics
in Biophysical journal (Print)
(literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori

Pagina inizio

Pagina fine

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume

Rivista

Note

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni

Univ Warsaw, Interdisciplinary Ctr Math & Computat Modeling, Warsaw, Poland; Scuola Normale Super Pisa, CNR, INFM, NEST, Pisa, Italy; Univ Calif San Diego, Dept Chem & Biochem, La Jolla, CA 92093 USA; Univ Calif San Diego, Ctr Theoret Biol Phys, La Jolla, CA 92093 USA; Univ Calif San Diego, Dept Pharmacol, La Jolla, CA 92093 USA; Univ Calif San Diego, Howard Hughes Med Inst, La Jolla, CA 92093 USA (literal)

Titolo

HIV-1 protease substrate binding and product release pathways explored with coarse-grained molecular dynamics (literal)

Abstract

We analyze the encounter of a peptide substrate with the native HIV-1 protease, the mechanism of substrate incorporation in the binding cleft, and the dissociation of products after substrate hydrolysis. To account for the substrate, we extend a coarse-grained model force field, which we previously developed to study the flap opening dynamics of HIV-1 protease on a microsecond timescale. Molecular and Langevin dynamics simulations show that the flaps need to open for the peptide to bind and that the protease interaction with the substrate influences the flap opening frequency and interval. On the other hand, release of the products does not require flap opening because they can slide out from the binding cleft to the sides of the enzyme. Our data show that in the protease-substrate complex the highest fluctuations correspond to the 17- and 39-turns and the substrate motion is anticorrelated with the 39-turn. Moreover, the active site residues and the flap tips move in phase with the peptide. We suggest some mechanistic principles for how the flexibility of the protein may be involved in ligand binding and release. (literal)

Prodotto di