HIV‐1 Integrase–DNA Models

Liao, Chenzhong; Nicklaus, Marc C.

doi:10.1002/9781118015377.ch28

Cited by 2 publications

(1 citation statement)

References 109 publications

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“…Model 10 was obtained after MD simulation of the tetramer and subsequent addition of the viral DNA models by means of a docking approach [105]. More information about models 1 – 10 is about to be published elsewhere [111]. …”

Section: Hiv-i In–dna Modelsmentioning

confidence: 99%

Computer Tools in the Discovery of HIV-1 Integrase Inhibitors

Liao

Nicklaus²

2010

Future Med. Chem.

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Computer-aided drug design (CADD) methodologies have made great advances and contributed significantly to the discovery and/or optimization of many clinically used drugs in recent years. CADD tools have likewise been applied to the discovery of inhibitors of HIV-I integrase, a difficult and worthwhile target for the development of efficient anti-HIV drugs. This article reviews the application of CADD tools, including pharmacophore search, quantitative structureactivity relationships, model building of integrase complexed with viral DNA and quantumchemical studies in the discovery of HIV-I integrase inhibitors. Different structurally diverse integrase inhibitors have been identified by, or with significant help from, various CADD tools.

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Section: Hiv-i In–dna Modelsmentioning

confidence: 99%

Computer Tools in the Discovery of HIV-1 Integrase Inhibitors

Liao

Nicklaus²

2010

Future Med. Chem.

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Computational design of a full-length model of HIV-1 integrase: modeling of new inhibitors and comparison of their calculated binding energies with those previously studied

Ercan

Pirinccioglu

2013

J Mol Model

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A full-length model of integrase (IN) of the human immunodeficiency virus type 1 (HIV-1) was constructed based on the distinctly resolved X-ray crystal structures of its three domains, named N-terminal, catalytic core and C-terminal. Thirty-one already known inhibitors with varieties of structural differences as well as nine newly tested ones were docked into the catalytic core. The molecular dynamic (MD) and binding properties of these complexes were obtained by MD calculations. The binding energies calculated by molecular mechanic/Poisson Boltzmann solvation area were significantly correlationed with available IC50. Four inhibitors including two newly designed were also docked into the full-length model and their MD behaviors and binding properties were calculated. It was found that one of the newly designed compounds forms a better complex with HIV-1 IN compared to the rest including raltegravir. MD calculations were performed with AMBER suite of programs using ff99SB force field for the proteins and the general Amber force field for the ligands. In conclusion, the results have produced a promising standpoint not only in the construction of the full-length model but also in development of new drugs against it. However, the role of multimer formation and the involvement of DNAs, and their subsequent effect on the complexation and inhibition, are required to arrive at a conclusive decision.

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HIV‐1 Integrase–DNA Models

Cited by 2 publications

References 109 publications

Computer Tools in the Discovery of HIV-1 Integrase Inhibitors

Computer Tools in the Discovery of HIV-1 Integrase Inhibitors

Computational design of a full-length model of HIV-1 integrase: modeling of new inhibitors and comparison of their calculated binding energies with those previously studied

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