Inhibitors computer-aided design

Chung F. Wong (University of Houston) and J. A. McCammon Enzymes and Inhibitors Computer-Aided Design. ... 

Computer-aided inhibitor design is a relatively new and powerful approach for the development of novel, potentially potent, nonsubstrate-analogue enzyme inhibitors. Computer-aided methods and biological screening can each lead to new classes of novel inhibitors. However, computer-aided design methods can focus the search for inhibitors, thereby circumventing much of the time-consuming synthetic and natural product purification procedures for those compounds they find unlikely to function as inhibitors. 

Jorgensen, W. L. Ruiz-Caro, J. Tirado-Rives, J. Basavapathruni, A. Anderson, K. S. Hamilton, A. D. Computer-aided design of non-nucleoside inhibitors of HIV-1 reverse transcriptase. Bioorg. Med. Chem. Lett. 2006,16, 663-667... 

Bohm, H.-J. The computer program LUDl a new method for the de novo design of enzyme inhibitors. /. Comput.-Aided Mol. Des. 1992, 6, 61-78. 

Tan JJ, Zhang B, Cong XJ et al (2011) Computer-aided design, synthesis, and biological activity evaluation of potent fusion inhibitors targeting HIV-1 gp41. Med Chem 7 309-316... 

Grembecka J, Sokalski WA, Kedzierski P (2000) Computer-aided design and activity prediction of leucitine aminopeptidase inhibitors. J Comput Aided Mol Des 14 531-544... 

In the next step, phosphinothricin was chosen as a lead compound for designing novel inhibitors.96 This structure has some advantages as a lead. It is the compound of a high potency combined with a relatively simple structure, which could be easily modified in several ways. Moreover, crystal structure of PPT-GS complex was solved,94 and thus it could be used as a template for rational, computer-aided design of novel inhibitors. 

A, Anderson KS, Hamilton AD. Computer-aided design of non-nucleoside inhibitors of HIV-1 reverse transcriptase. Bioorg. 

Desiraju GR, Gopalakrishnan B, Jetti RKR, Nagaraju A, Raveendra D, Sarma JARP, et al. Computer-aided design of selective COX-2 inhibitors Comparative molecular field analysis, comparative molecular similarity indices analyses, and docking studies of some 1,2-diarylimidazole derivatives. J Med Chem 2002 45 4847-57. 

The computer-aided design of potent inhibitors of influenza virus sialidase based on a crystal structure of the enzyme has been described. A combination of manual molecular graphics analysis and the de novo ligand design tool GRID was used to identify modifications to the... 

Park, H. and Lee, S. 2004. Homology modeling, force field design, and free energy simulation studies to optimize the activities of histone deacetylase inhibitors. /. Comput. Aid. Mol. Des., 18,375-388. 

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J1992. LUDI - Rule-Based Automatic Design of New Substituents for Enzyme Inhibitor Leads. mal of Computer-Aided Molecular Design 6 593-606. 

Bohm HJ, Banner DW, Weber L. Combinatorial docking and combinatorial chemistry design of potent non-peptide thrombin inhibitors. J Comput Aided Mol Design 1999 13 51-6. 

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A recent report from the U. K. deals with 1,4-bis(oxodihydropyridazin-yl)benzenes and congeners which are also potent phosphodiesterase inhibitors and inodilators [159], This investigation, together with computer-aided modelling studies on various phosphodiesterase III inhibitors [160], may well stimulate the rational design of additional pyridazine-derived inodilators. 

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