Large-scale motions and electrostatic properties of furin and HIV-1 protease

V. Carnevale, Simone Raugei, C. Micheletti, P. Carloni

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

We present a comparative study between two members of serine and aspartic proteases complexed with a peptide substrate. The same computational setup is used to characterize the structural, electrostatic, and electronic properties for the Michaelis complex of furin, a serine protease, and of the aspartic protease from HIV-1. In both cases plane-wave density functional theory (PW-DFT) and empirical force-field-based molecular dynamics calculations are used. For furin, calculations are extended to the complex with the intermediate of the first step of the reaction. Comparisons are also made with results from recent PW-DFT investigations on both families of enzymes and with the same chemical groups in an aqueous environment. It is found that the substrate carbonyl group is more polarized in the furin complex than in the HIV-1 protease one. A further difference regards the large-scale motions of the complexes as a whole and local conformational fluctuations at the active site. The global and local fluctuations are well coupled for HIV-1 protease but not for furin. Thus, despite some chemical analogies in the first step of the reaction mechanism, furin and HIV-1 protease complexes appear to be characterized by a different interplay of electrostatics and conformational fluctuations.

Original languageEnglish
Pages (from-to)12327-12332
Number of pages6
JournalJournal of Physical Chemistry A
Volume111
Issue number49
DOIs
Publication statusPublished - Dec 13 2007

Fingerprint

Furin
protease
human immunodeficiency virus
Electrostatics
electrostatics
Density functional theory
plane waves
density functional theory
Serine Proteases
Substrates
Electronic properties
Serine
Molecular dynamics
Peptide Hydrolases
field theory (physics)
peptides
Human immunodeficiency virus 1 p16 protease
enzymes
Peptides
molecular dynamics

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry

Cite this

Large-scale motions and electrostatic properties of furin and HIV-1 protease. / Carnevale, V.; Raugei, Simone; Micheletti, C.; Carloni, P.

In: Journal of Physical Chemistry A, Vol. 111, No. 49, 13.12.2007, p. 12327-12332.

Research output: Contribution to journalArticle

Carnevale, V. ; Raugei, Simone ; Micheletti, C. ; Carloni, P. / Large-scale motions and electrostatic properties of furin and HIV-1 protease. In: Journal of Physical Chemistry A. 2007 ; Vol. 111, No. 49. pp. 12327-12332.
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