Conformational drug design

Subject Drugs--Design. Drugs--Structure-activity relationships. Drugs—Conformation. Drug Design. Structure-Activity Relationship. 

Since the summation in Eq. (12) may be on any subset of atoms, it can be fine-tuned to best suit the problem at hand. The summation may be over the whole molecule, but it is very common to calculate conformational distances based only on non-hydrogen heavy atoms or, in the case of proteins, even based on only the backbone Ca atoms. Alternatively, in a study related to drug design one may consider, for example, focusing only on atoms that make up the pharmacophore region or that are otherwise known to be functionally important. 

GR Marshall, CD Barry, HE Bosshard, RA Dammkoehler, DA Dunn. The conformational parameter m drug design The active analog approach. ACS Symp Ser 112 205-226, 1979. YC Martin. Overview of concepts and methods in computer-assisted rational drug design. Methods Enzymol 203 587-613, 1991. 

Marshall GR, Barry CD, Bosshard HE, Dammkoehler RA, Dunn DA. The conformational parameter in drug design The active analog approach. Computer-assisted drug design. ACS Symposium Series 112. Washington DC American Chemical Society, 1979. p. 205-26. 

Very often, it is unknown which conformahon of a flexible molecule is needed. For example, in drug design, we hunt often for the so-called bioachve conformation, which is the molecule in its receptor-bound state. In this case, any other experimental structure of the isolated molecule - in vacuum, in soluhon or in crystal - can be the wrong choice. 

Woody, R.W. (1985) Conformation in Biology and Drug Design, Academic Press, Orlando, pp. 15-114. 

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