Protein-ligand scoring functions

Wang B, Westerhoff LM, Merz KM Jr (2007) A critical assessment of the performance of protein-ligand scoring functions based on NMR chemical shift perturbations. J Med Chem 50(21) 5128-5134... 

Bdhm H-J 1994 The development of a simple empirical scoring function to estimate the binding constant for a protein-ligand complex of known three-dimensional structure J. Comp.-Aided Mol. Design 8 243-56... 

Ferrara P, Gohlke H, Price DJ, Klebe G, Brooks CL. Assessing scoring functions for protein-ligand interactions. J Med Chem 2004 47 3032-47. 

Raha K, Merz KM. Large-scale validation of a quantum mechanics based scoring function predicting the binding affinity and the binding mode of a diverse set of protein-ligand complexes. J Med Chem 2005 48 4558-75. 

CombiSMoG potential function, which was derived from 1000 protein-ligand complex 3D structures. After inspection of 100,000 candidates, the hve best hits were ranked by a force field calculation. The (i )-isomer of the indole compound 59 (K = 30 pM Fig. 16.8) is the highest-scoring compound and has the highest affinity of all synthesized molecules, whereas the (S) -isomer has only K = 230 pM [131,132]. 

As discussed in the introduction, scoring functions still pose problems (see also Chapter 14). Some of these problems arise from insufficient consideration of details of favorable and unfavorable protein-ligand interactions. 

Muegge I, Martin YC. A general and fast scoring function for protein-ligand interactions a simplified potential approach. J Med Chem 1999 42 791-804. 

Gohlke H, Hendlich M, Klebe G. Knowledge-based scoring function to predict protein-ligand interactions. J Mol Biol 2000 295 337-56. 

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