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Conformational motions of HIV-1 protease identified using reversible digitally filtered molecular dynamics

Conformational motions of HIV-1 protease identified using reversible digitally filtered molecular dynamics
Conformational motions of HIV-1 protease identified using reversible digitally filtered molecular dynamics
HIV-1 protease performs a vital step in the propagation of the HIV virus and is therefore an important drug target in the treatment of AIDS. It consists of a homodimer, with access to the active site limited by two protein flaps. NMR studies have identified two time scales of motions that occur in these flaps, and it is thought that the slower of these is responsible for a conformational change that makes the protein ligand-accessible.

This motion occurs on a time scale outside that achievable using traditional molecular dynamics simulations. Reversible Digitally Filtered Molecular Dynamics (RDFMD) is a method that amplifies low frequency motions associated with conformational change and has recently been applied to, among others, E. coli dihydrofolate reductase, inducing a conformational change between known crystal structures.

In this paper, the conformational motions of HIV-1 protease produced during MD and RDFMD simulations are presented, including movement between the known semiopen and closed conformations, and the opening and closing of the protein flaps.
1549-9618
1117-1128
Wiley, Adrian P.
f35459c6-40b2-4572-acb6-669fca3b13f7
Williams, Sarah L.
2ca47995-0368-4353-86b1-9d5946f83c34
Essex, Jonathan W.
1f409cfe-6ba4-42e2-a0ab-a931826314b5
Wiley, Adrian P.
f35459c6-40b2-4572-acb6-669fca3b13f7
Williams, Sarah L.
2ca47995-0368-4353-86b1-9d5946f83c34
Essex, Jonathan W.
1f409cfe-6ba4-42e2-a0ab-a931826314b5

Wiley, Adrian P., Williams, Sarah L. and Essex, Jonathan W. (2009) Conformational motions of HIV-1 protease identified using reversible digitally filtered molecular dynamics. Journal of Chemical Theory and Computation, 5 (4), 1117-1128. (doi:10.1021/ct800152d).

Record type: Article

Abstract

HIV-1 protease performs a vital step in the propagation of the HIV virus and is therefore an important drug target in the treatment of AIDS. It consists of a homodimer, with access to the active site limited by two protein flaps. NMR studies have identified two time scales of motions that occur in these flaps, and it is thought that the slower of these is responsible for a conformational change that makes the protein ligand-accessible.

This motion occurs on a time scale outside that achievable using traditional molecular dynamics simulations. Reversible Digitally Filtered Molecular Dynamics (RDFMD) is a method that amplifies low frequency motions associated with conformational change and has recently been applied to, among others, E. coli dihydrofolate reductase, inducing a conformational change between known crystal structures.

In this paper, the conformational motions of HIV-1 protease produced during MD and RDFMD simulations are presented, including movement between the known semiopen and closed conformations, and the opening and closing of the protein flaps.

Full text not available from this repository.

More information

Published date: 2009

Identifiers

Local EPrints ID: 149183
URI: http://eprints.soton.ac.uk/id/eprint/149183
ISSN: 1549-9618
PURE UUID: d211ff5b-0bd3-4632-a034-d9d51a24098b
ORCID for Jonathan W. Essex: ORCID iD orcid.org/0000-0003-2639-2746

Catalogue record

Date deposited: 30 Apr 2010 09:14
Last modified: 20 Jul 2019 01:20

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