Ligand binding predicting energies

Mobley, D.L., Graves, A.P., Chodera, J.D., McReynolds, A.C., Shoichet, B.K., Ml, K.A. Predicting absolute ligand binding free energies to a simple model site, J. Mol. Biol. 2007, in press. 

Ajay and Murcko, 1995] Ajay, ajid Murcko, M. Computational methods to predict binding free energy in ligand-receptor complexes. J. Med. Chem. 38 (1995) 4953-4967... 

Hansson T, J Mturelius and J Aqvist 1998. Ligand Binding Affinity Prediction by Linear InteracHor Energy Methods. Journal of Computer-Aided Molecular Design 12 27-35. 

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. 

Errors of this magnitude make the useful prediction of free energies a difficult task, when differences of only one to three kcal/mol are involved. Nevertheless, within the error limits of the computed free energy differences, the trend is that relative to 8-methyl-N5-deazapterin or 8-methyl-pterin, the compounds methyl substituted in the 5, 6 or 7 positions are thermodynamically more stable when bound to DHFR largely by virtue of a hydrophobic effect, i.e. methyl substitution reduces the affinity of the ligand for the solvent more than it reduces affinity for the DHFR active-site. The stability of ligand binding to DHFR appears to be optimal with a 6-methyl substituent additional 5-methyl and/or 7-methyl substitution has little effect... 

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