Docking molecular

The automated molecular docking calculations were carried out using AutoDock 

Operator weights for crossover, mutation, and elitism were 0.80, 0.02, and 1, respectively. The docked complexes of the inhibitor-enzyme were selected according to the criterion of interaction energy combined with geometrical and electronic matching quality. 

Fig 12 22 The DOCK algorithm [Kmtz et al. 1982], Atoms are matched to sphere centres and then the molecule is positioned within the binding site 

Genetic algorithms can also be used to perform molecular docking [Judson et al. 1994 Jones et al. 1995b Oshiro et al. 1995]. Each chromosome codes not only for the internal conformation of the ligand as described in Section 9.9.1 but also for the orientation of the ligand within the receptor site. Both the orientation and the internal corrformation will thus vary as the populations evolve. The score of each docked structure within the site acts as the fitness function used to select the individuals for the next iteration. 

The weighting factors can then be fitted to actual binding data for specific protein-ligand systems. 

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Strynadka et al., 1996] Strynadka, N., Eisenstein, M., Katchalski-Katzir, E., Shoichet, B., Kuntz, I., Abagyan, R., Totrov, M., Janin, J., Cherflls, J., Zimmerman, F., Olson, A., Duncan, B., Rao, M., Jackson, R., Sternberg, M., and James, M. Molecular docking programs successfully predict the binding of a /3-lactamase inhibitory protein to TEM-1 /3-lactamase. Nature Struct. Biol. 3 (1996) 233-239... 

TJA Ewing, ID Kuntz. Critical evaluation of search algorithms for automated molecular docking and database screening. J Comput Chem 18 1175-1189, 1997. 

DA Gschwend, AC Good, ID Kuntz. Molecular docking towards drug discovery. I Mol Re-cogn 9(2) 175-186, 1996. 

Erickson JA, Jalaie M, Robertson DH, Lewis RA, Vieth M. Lessons in molecn-lar recognition the effects of ligand and protein flexibility on molecular docking accuracy. J Med Chem 2004 47 45-55. 

Wang R, Lu Y, Wang S. Comparative evaluation of 11 scoring functions for molecular docking. J Med Chem 2003 46 2287-303. 

Doman TN, McGovern SL, Witherbee BJ, Kasten TP, Kurumbail R, Stallings WC, Connolly DT, Shoichet BK. Molecular docking and high throughput screening for novel inhibitors of protein tyrosine phosphatase IB. J Med Chem 2002 45 2213-21. 

Rastelli G, Ferrari AM, Constantino L, Gamberini MC. Discovery of new inhibitors of aldose reductase from molecular docking and database screening. Bioorg Med Chem 2002 10 1437-50. 

Burkhard P, Hommell U, Sanner M, Walkinshaw MD. The discovery of steroids and other novel FKBP inhibitors using a molecular docking program. J Mol Biol 1999 287 853-8. 

Ewing TJ, Makino S, Skillman AG, Kuntz ID. DOCK 4.0 search strategies for automated molecular docking of flexible molecule databases. J Comput Aided Mol Dei 2001 15 411-28. 

Frederick, R. Robert, S. Charlier, C. de Ruyck, J. Wouters, J. Masereel, B. Pochet, L. Mechanism-based thrombin inhibitors design, synthesis, and molecular docking of a new selective 2-OXO-2/7- l-benzopyxan derivative. J. Med. Chem. 2007, 50, 3645-3650. 

Shoichet, B., Bodian, D., Kuntz, I., Molecular docking using shape descriptors, J. Corn-put. Chem. 1992,13, 380-397... 

Claussen, H., Buning, C., Rarey, M., Lengauer, T., FlexE efficient molecular docking considering protein structure variations, J. Mol. Biol. 2001, 308, 377-395... 

Keywords Alzheimer s disease, AD therapeutics, Molecular dynamics, Molecular docking References ... 

Figure 3.6 Docking simulations. (Source Liu H, Huang X, Shen J, et al. Inhibitory mode of 1,5-diarylpyrazole derivatives against cyclooxygenase-2 and cyclooxygenase-1 molecular docking and 3D QSAR analyses, Journal of Medicinal Chemistry 45 4816-4827 (2002). Used with permission.)...

Molecular Docking of Ligands Against Target Receptors... 

Table 3.2 Most commonly used molecular docking programs [22]...

Oshiro C, Bradley EK, Eksterowicz J, Evensen E, Lamb ML, et al. 2004. Performance of 3D-database molecular docking studies into homology models. J Med Chem 47(3) 764-767. 

Shoichet BK, McGovern SL, Wei B, Irwin JJ. 2002. Lead discovery using molecular docking. Curr Opin Chem Biol 6(4) 439-446. 

Molecular docking (structure-based virtual screening) on the basis of a target protein structure, ligand molecules that bind to the active site of the target are searched for. 

For most of the classes, recent review articles can easily be found Molecular docking [6-10], Structural alignments [11, 12], Molecular similarity [13-15], Pharmacophore mapping [16-18]. 

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