Automated site-directed drug design: a general algorithm for knowledge acquisition about hydrogen-bonding regions at protein surfaces
- 22 March 1989
- journal article
- research article
- Published by The Royal Society in Proceedings of the Royal Society of London. B. Biological Sciences
- Vol. 236 (1283) , 101-113
- https://doi.org/10.1098/rspb.1989.0015
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.This publication has 11 references indexed in Scilit:
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