Protein-ligand docking computational

Herein lie two fairly different approaches to this problem. One approach considers the computational tractability to be paramount, and in this case, one is willing to sacrifice accuracy for tractability. Protein-ligand docking is an example of this approach, and due to its tractability, has become a very prevalent means to quickly assay how well a ligand can bind to a protein. 

Verdonk, M. L., Berdini, V, Hartshorn, M. J., Mooij, W. T., Murray, C. W., Taylor, R. D., Watson, P. (2004) Virtual screening using protein-ligand docking avoiding artificial enrichment. T Chem Inf Comput Sci 44, 793-806. 

Control the size of the enumerated library As the name implies, combinatorial libraries can explode in size very quickly. Therefore one must perform reactant-level selections before product enumeration in most design cases. As shown in the example library, molecular weight (MW) is an effective filter to cut down number of reactants, so is reactant availability inside the reactant inventory system. As a matter of principle, more expensive computational approaches (e.g., protein-ligand docking and scoring) should be applied only to smaller subsets of reactants or products. 

M. Rarey, B. Kramer, T. Lengauer, G. Klebe. Multiple automatic base selection Protein-ligand docking based on incremental construction without manual intervention. J. Comput.-Aided Mol. Des.,... 

Computational protein-ligand docking is widely used nowadays to select compounds for biological screening [23], In the field of ADME/Tox, where... 

Zavodszky MI, Sanschagrin PC, Korde RS, Kuhn LA. Distilling the essential features of a protein surface for improving protein-ligand docking, scoring, and virtual screening. J Comput Aided Mol Des 2002 16(12) 883-902. 

Molecular dynamics methods are primarily used for the refinement of structural models (Li et al., 1997) or the analysis of molecular interactions (Cappelli et al., 1996 Kothekar et al., 1998). In both cases the time scales to be simulated are within range of current computing technology. Another application area is the study of allosteric movements of proteins (Tanner et al., 1993). Molecular Dynamics approaches to protein-ligand docking are described in Chapter 7 of Volume I. 

Verdonk ML, Berdini V, Hartshorn MJ et al (2004) Virtual screening using protein-ligand docking avoiding artificial enrichment. J Chem Inf Comput Sci 44 793-806... 

In order to perform computational protein-ligand docking experiments, a 3-D structure of the target protein at atomic resolution must be available. The most reliable sources are crystal and solution structures provided by the Protein Data Bank (PDB) [7] or from in-house efforts. Homology models [27,28] and pseudoreceptor models [29] are an alternative in the absence of experimental structures. It should be cautioned, however, that the quality of the protein structure is crucial for the success of subsequent docking experiments. Even small changes in structure can drastically alter... 

Taufer. M.. Armen, R., Chen, J.,Teller, P., and Brooks, C. (2009) Computational multiscale modeling in protein-ligand docking. IEEE Engineering in Medicine and Biology Magazine, 28, 58—69. 

Taufer M et al (2005) Study of an accurate and fast protein-ligand docking algorithm based on molecular dynamics. Concurr Comput 17(14) 1627-1641... 

Tao P, Lai L (2001) Protein ligand docking based on empirical method for binding affinity estimation. J Comput Aided Mol Des 15(5) 429 146... 

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