A knowledge-based scoring function for protein-ligand interactions: Probing the reference state
- 165 Downloads
Knowledge-based scoring functions have recently emerged as an alternative and very promising way of ranking protein-ligand complexes with known 3D structure according to their binding affinities. Theses implified potential-based approaches use the structural information stored in databases of protein-ligand complexes to derive atom pair interaction potentials also known as potentials of mean force (PMF). The derived PMF depend on the definition of a suitable reference state. The reference states vary among suggested knowledge-based scoring functions. Therefore, we attempt here to shed some light on the influence of different reference state definitions on the predictive power of a knowledge-based scoring function that has been introduced by us very recently [J. Med. Chem., 42 (1999) 791]. It is shown that a reference state that implicitly and more comprehensively accounts for protein and ligand solvation gives the most consistent scoring results for four test sets of diverse protein-ligand complexes taken from the Brookhaven Protein Data Bank. It is also shown that a reference sphere radius of at least 7–8 Å is needed to effectively capture solvation effects that are treated implicitly in the scoring function.
Unable to display preview. Download preview PDF.
- 1.Dixon, J.S. and Blaney, J.M., Designing Bioactive Molecules. In: Three-dimensional techniques and applications, Martin, Y. C. and Willett, P., (Eds.) American Chemical Society, Washington, DC, 1998, pp. 175–197.Google Scholar
- 19.Zou, X., personal communication.Google Scholar
- 31.Muegge, I., Med. Chem. Res., 7-8 (1999) 490.Google Scholar
- 42.Press, W.H., Teukolsky, S.A., Vetterling, W.T. and Flannery, B.R., Numerical Recipes, University Press, Cambridge, 1986.Google Scholar