eprintid: 161
rev_number: 4
eprint_status: archive
userid: 6
dir: disk0/00/00/01/61
datestamp: 2008-10-07
lastmod: 2015-05-29 19:48:26
status_changed: 2009-04-08 16:55:03
type: report
metadata_visibility: show
item_issues_count: 0
creators_name: Bona, Andrej
creators_name: Laflamme, Claude
contributors_name: Batten, Lynn
contributors_name: Bohun, C. Sean
contributors_name: Doman, Tom
contributors_name: Drew, John
contributors_name: Edwards, Rod
contributors_name: Kutay, Susan
contributors_name: McCrea, Devon
contributors_name: Myrvold, Wendy
contributors_name: Ruskey, Frank
contributors_name: Sawada, Joe
contributors_name: van den Driessche, Pauline
contributors_name: Vander Kloet, Jana
contributors_name: Wood, Kathryn L. B.
title: Classification of Chemical Compound Pharmacophore Structures
ispublished: pub
subjects: medicine
studygroups: ipsw3
companyname: Searle Corporation
full_text_status: public
abstract: A pharmacophore is a structural abstraction of the interactions between various functional group types in a compound. They are described by a spatial representation of these groups as centres (or vertices) of geometrical polyhedra, together with pairwise distances between distances.

We provide an analysis that facilitates counting 3 and 4 centre pharmacophores, including a mathematical model for distance interval ratios, triangle and other inequality requirements for feasible triangles and tetrahedra, and symmetries. 

Beside spatial symmetries and and distance similarities for each edge of the polyhedra, there does not appear to be any other relevant structural similarity feature between two pharmacophores that can be used to reduce the classification of a typical compound.
problem_statement: There is a staggeringly large number of "drug-like" chemical compounds that can be made, but to date only a tiny fraction have been made and characterized.

The main hope in a classification is the existence of a similarity pattern in the chemical structures, called "pharmacophore". Compounds matching the same pharmacophore interact with biological molecules (enzymes, receptors, etc) in a similar fashion, and a classification of these pharmacophores would be considered an enormous breakthrough in drug discovery.

An immediate question is to estimate the number of pharmacophores. Mathematically, this is a question about how a an object with a small, fixed number of pharmacophoric features fills a cavity, but also an exploration of the minimum set of objects required to display all pharmacophoric elements in all possible geometric arrangements.
date: 1999
date_type: published
pages: 11
citation:   Bona, Andrej and Laflamme, Claude  (1999) Classification of Chemical Compound Pharmacophore Structures.  [Study Group Report]     
document_url: http://miis.maths.ox.ac.uk/miis/161/1/pharmacophore.pdf