Ligand-based virtual screening applications

There is no standard procedure for structure- or ligand-based virtual screening. Every prospective application requires understanding and tuning of key parameters. AH... 

Geppert H, Vogt M, Bajorath J (2010) Current trends in ligand-based virtual screening molecular representations, data mining methods, new application areas, and performance evaluation. J Chem Inf Model 50(2) 205-216... 

The first section provides an overview of successful structure-based virtual screening applications, followed by some comments on structure-based library design. This is followed by a summary of recent ligand-based virtual screening examples. Within each section, examples are organized by target families to focus on successes and challenges in different areas relevant to medicinal chemistry. 

Tresadern, G., Bemporad, D., and Howe, T. (2009) A Comparison of ligand based virtual screening methods and application to corticotropin releasing factor 1 receptor. Journal of Molecular Graphics and Modelling, 27, 860-870. 

Hessler G, Zimmermann M, Matter H, et al. Multiple-ligand-based virtual screening Methods and applications of the MTree approach. J Med Chem 2005 48 6575-6584. 

Virtual screening applications based on superposition or docking usually contain difficult-to-solve optimization problems with a mixed combinatorial and numerical flavor. The combinatorial aspect results from discrete models of conformational flexibility and molecular interactions. The numerical aspect results from describing the relative orientation of two objects, either two superimposed molecules or a ligand with respect to a protein in docking calculations. Problems of this kind are in most cases hard to solve optimally with reasonable compute resources. Sometimes, the combinatorial and the numerical part of such a problem can be separated and independently solved. For example, several virtual screening tools enumerate the conformational space of a molecule in order to address a major combinatorial part of the problem independently (see for example [199]). Alternatively, heuristic search techniques are used to tackle the problem as a whole. Some of them will be covered in this section. 

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