TY - JOUR
T1 - Constrained search of conformational hyperspace
AU - Dammkoehler, Richard A.
AU - Karasek, Steven F.
AU - Shands, E. F.Berkley
AU - Marshall, Garland R.
PY - 1989/3
Y1 - 1989/3
N2 - We introduce a new method for determining pharmacophore or active site geometries by analysis of the structures of a series of active compounds. The method, constrained search, and the key concepts on which it is based, is described and illustrated by its application to 28 potent inhibitors of angiotensin-converting enzyme (ACE). The data set is one utilized by Mayer et al. [J. Comput.-Aided Mol. Design, 1 (1987) 3-16] to determine a unique geometry for the active site. Our experiment validated the previously reported results, obtained by a systematic search, while reducing the computer time requirement by more than two orders of magnitude. The experiment also identified a previously unrecognized alternative active site geometry for the ACE series.
AB - We introduce a new method for determining pharmacophore or active site geometries by analysis of the structures of a series of active compounds. The method, constrained search, and the key concepts on which it is based, is described and illustrated by its application to 28 potent inhibitors of angiotensin-converting enzyme (ACE). The data set is one utilized by Mayer et al. [J. Comput.-Aided Mol. Design, 1 (1987) 3-16] to determine a unique geometry for the active site. Our experiment validated the previously reported results, obtained by a systematic search, while reducing the computer time requirement by more than two orders of magnitude. The experiment also identified a previously unrecognized alternative active site geometry for the ACE series.
KW - Active analog approach
KW - Active site geometry
KW - Angiotensin converting enzyme
KW - Pharmacophore
KW - Systematic search
UR - http://www.scopus.com/inward/record.url?scp=0024635625&partnerID=8YFLogxK
U2 - 10.1007/BF01590992
DO - 10.1007/BF01590992
M3 - Article
C2 - 2715794
AN - SCOPUS:0024635625
VL - 3
SP - 3
EP - 21
JO - Journal of Computer-Aided Molecular Design
JF - Journal of Computer-Aided Molecular Design
SN - 0920-654X
IS - 1
ER -