Abstract
This is the first of four papers that begin to explore the possibility of automated site-directed drug design. A general outline is given of the logical steps involved in approaching the problem. The starting point is the process of knowledge acquisition about the site. An algorithm is described here for the construction of a map of hydrogen-bonding regions at protein surfaces directly from the Brookhaven Protein Data Bank coordinates. Hydrogen-bonding atoms are located, intramolecular bonds are searched for, hydrogen-bonding atoms at the surface are found and hydrogen-bonding regions are computed at the accessible surface. A grid is placed within each region discovered and the probability of hydrogen bonding at each grid point is computed. The output of the program is a map of hydrogen-bonding regions displayed within a user-defined window. This information can be used as part of a knowledge base for the automatic construction of novel ligands to fit specified binding sites.
Reference19 articles.
1. Barr A. & Feigenbaum E. A. 1982 The handbook of artificial intelligence vols 1and 2. London : Pitman.
2. The protein data bank: a computerbased archival technique for macromolecular structures. J. molec;Bernstein F. C.;Biol.,1977
3. AsurveyofO-H --0 hydrogen bond geometries determined by neutron diffraction. J. molec;Ceccarelli C..;Struct.,1981
4. Automated site-directed drug design : the prediction and observation of ligand point positions at hydrogen-bonding regions on protein surfaces
5. Dean P. M. 1987 Molecular foundations of drug-receptor interaction. Cambridge University Press.
Cited by
101 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献