CINF 14 [ 499453 ] : Prospective Evaluation of Structure-based ADME Predictions : Knowing When the Experiment is the Prudent Course of Action
3D-pharmacophores have become popular in the last decade as descriptors for chemical similarity searching and combinatorial library design. These pharmacophores are typically encoded in large bitstrings, up to hundreds of millions of bits long. Research on other classes of chemical descriptors suggests that "chemical space" requires on the order of 10-20 dimensions. Many of the millions of dimensions are correlated or irrelevant and their large size makes them a less efficient representation for computation. We have developed an approach based on classical multidimensional scaling to determine the inherent dimensionality of these large chemical bitstrings (pharmacophore or otherwise), resulting in real-valued cartesian coordinates. We have also developed a novel approach to calculate much smaller bitstrings (hundreds of bits) that preserve the original pairwise similarity of the original large bitstrings. The new smaller space is general enough that it can be used for many common descriptor-based library design approaches: coverage, diversity, D-optimal, or informative design. CINF 2 [522224]: A hierarchy of structure representation Johann Gasteiger, Thomas Kleinöder, Jens Sadowski, Markus Wagener, and Markus C. Hemmer, ComputerChemie-Centrum and Institute of Organic Chemistry, University of Erlangen-Nuremberg, Naegelsbachstr. 25, Erlangen 91052, Germany, Fax: +49-9131-85 26566, Gasteiger@chemie.uni-erlangen.de ACCEPTED Topic Selection: Chemical Descriptors: I Invited: Y Preferred Presentation Format: OralOnly Consider for Sci-Mix: N Conforms to Bylaw 6: Y Last Modified: 2001-12-13 Abstract Modern drug design generates massive amounts of data that have to be related to chemical structures. Therefore, methods are needed that encode the physicochemical effects of chemical structures responsible for Abstract Listing Page 1 of 47 CINFAbstract ListingModern drug design generates massive amounts of data that have to be related to chemical structures. Therefore, methods are needed that encode the physicochemical effects of chemical structures responsible for Abstract Listing Page 1 of 47 CINFAbstract Listing