Docking validation

Jones G, P Willett, R C Glen, A R Leach and R Taylor 1997. Development and Validation of a Geneti Algorithm for Flexible Docking. Journal of Molecular Biology 267 727-748. 

Inosine 5 -Monophosphate Dehydrogenase. A series of 21 known inosine 5 -monophosphate dehydrogenase (IMPDH) inhibitors was used to validate a virtual screening protocol. By application of a molecular weight filter (80 < MW < 400), 3425 compounds were extracted from an in-house reagent inventory system. Docking of these compounds into a substrate-IMPDH complex 3D structure was performed with the program FlexX three... 

Figure 23.2 The SmartPen system is a pen with an optical sensor that records each keystroke on a special form. The pen is docked at a computer or data can be wirelessly transmitted, and data from anywhere in the world are immediately sent for validation. Queries are generated within minutes, closing the feedback loop and markedly rednc-ing query rates as compared to conventional systems.

Alcaro, S. et al., A quasi-flexible automatic docking processing for studying stereoselective recognition mechanisms. Part 1. Protocol validation, J. Comp. Chem., 21,515, 2000. 

Jones G, Willett P, Glen AR, Taylor R. 1997. Development and validation of a genetic algorithm for flexible docking. J Mol Biol 267(3) 727-748. 

X-ray crystallography, docking modes can be validated by various NMR techniques NOEs may be observed between the ligand and the receptor protein by heteronuclear-filtered NOE spectroscopy [51], chemical shift changes of protein resonances upon binding can be analyzed by simulation of shifts caused by ring currents and electrostatic effects [52], and saturation transfer difference measurements indicate which part of the ligand is in direct contact with the protein [52]. 

There has been considerable discussion on the validity of docking and scoring functions in structure-based design because of the complex issues involved such as ligand orientation, water participation, or flexibility of the target protein itself [186-190]. 

Another retrospective analysis of already known H DAC inhibitors was carried out by You et al. [68]. They generated a 3D chemical-feature-based pharmacophore model and compared the ligand-based model with the structural-functional requirements for the binding of the HDAC inhibitors. Using this model, the interactions between the benzamide MS-275 and HDAC were explored. The result showed that the type and spatial location of chemical features encoded in the pharmacophore are in full agreement with the enzyme-inhibitor interaction pattern identified from molecular docking. However, also in this study no experimental validation of the modeling results was provided. 

Moustakas, D.T., Lang, P.T., Pegg, S., Pettersen, E., Kuntz, l.D. et al. (2006) Development and validation of a modular, extensible docking program DOCK 5. Journal of Computer-Aided Molecular Design, 20, 601-619. 

Tietze, S., Apostolakis, J. (2007) GlamDock development and validation of a new docking tool on several thousand protein-ligand complexes. J Chem Inf Model 47, 1657-1672. 

In the validation study by Hawkins et al. (60), the shapematching method ROCS was compared to 7 well-known docking tools, in terms of their abilities to recover known ligands for 21 different protein targets. The comparative study showed that the 3D shape method (ROCS) performed at least the same as, and often better than, the docking tools studied. Their work indicated that shape-based virtual screening method could be both efficient (in terms of the computational speed) and effective (in terms of hit enrichment) in virtual screening projects. 

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