Binding Mode Prediction

Virtual screening is a computational method that attempts to determine, for a set of molecules, which molecules are active against the target of interest. Virtual screening is the simplest of activity prediction tasks and asks only if the 

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Padgett, L. W., Howlett, A. C., Shim, J. Y. (2008) Binding mode prediction of con-formationally restricted anandamide analogs within the CB1 receptor. J Mol Signal 3, 5. 

F. R., Astruc-Diaz, F., Thompson, . M., Cavasotto, C. N., Naguib, M. (2009) 2,3-Dihydro-1-benzofuran derivatives as a series of potent selective cannabinoid receptor 2 agonists design, synthesis, and binding mode prediction through ligand-steered modeling. ChemMedChem 4, 1615-1629. 

In silico techniques have gained wide acceptance as a tool to support the drug discovery and optimization process. Binding mode predictions via docking, affinity predictions via QSAR and CoMFA, or the prediction of ADME(T) properties are routinely applied [1-3]. 

Table 2 The success rates for binding mode prediction and the correlation coefficients (R) for binding affinity prediction with seven knowledge-based scoring functions on Wang et al. s test set of 100 diverse protein-ligand complexes...

As mean-force potentials become increasingly accurate, they will serve as a valuable tool for structure-based drug design. Detailed analysis of the mean-force potentials will provide insightful hints on how to improve other physics-based scoring functions. Mean-force potentials that perform well on binding mode predictions may also be implemented for molecular dynamics simulations of protein-ligand interactions. 

Yongye, A. B., Appel, J. R., Giulianotti, M., Dooley, C. T., Medina-Franco, J. L., Nefzi, A., Houghten, R., and Martinez-Mayorga, K. (2009). Identification, binding mode prediction and structure-activity relationships of potent triamine and piperazine opioid ligands. 

Fischer, B., Basili, S., Merlitz, H., and Wenzel, W. (2007) Accuracy of binding mode prediction with a cascadic stochastic tunneling method. Proteins, 68, 195-204. 

G., and Vermeulen, N.P.E. (2005) Binding mode prediction of cytochrome P450 and thymidine kinase protein-ligand complexes by consideration of water and rescoring in automated docking. Journal of Medicinal Chemistry, 48, 2308-2318. 

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