Predicting Ligand Affinity

Because of the R variability and the high root mean square error (RMSE) values, we believe that MM-PBSA and MM-GBSA methods are generally not accurate enough to predict ligand affinity. 

So why, after 30 years of structure-based drug design method development, is predicting ligand affinity such a difficult and yet to be solved problem We would like to leave you with one last thought. Almost all of the protein receptor structural data used for ligand affinity prediction methods come from X-ray crystal structures. As every medicinal chemist knows, the conformation of a... 

Reddy MR, Erion MD, Agarwal A. Free energy calculations Use and limitations in predicting ligand binding affinities. In Lipkowitz KB, Boyd DB, editors. Reviews in Computational Chemistry, Vol. 16. New York Wiley-VCH, 2000. p. 217-304. 

Several different types of approaches for predicting ligand-binding affinities have been developed and a number of useful reviews of the field... 

M. Rami Reddy, Mark D. Erion, and Atul Agarwal, Free Energy Calculations Use and Limitations in Predicting Ligand Binding Affinities. 

Zamora, I., Oprea, T., Cruciani, G., Pastor, M., and Ungell, A.-L. Surface descriptors for protein-ligand affinity prediction. /. Med. Chem. 2003, 46, 25-33. 

Predicting ligand binding to proteins by affinity fingerprinting. Chem. Biol. 1995,... 

Predicting binding affinities of protein ligands from three-dimensional models application to peptide binding to Class I major histocompatibility proteins. 

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