Chemodiversity and molecular plasticity: recognition processes as explored by property spaces.

Details

Serval ID
serval:BIB_C75E133F4199
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Chemodiversity and molecular plasticity: recognition processes as explored by property spaces.
Journal
Future Medicinal Chemistry
Author(s)
Vistoli G., Pedretti A., Testa B.
ISSN
1756-8927 (Electronic)
ISSN-L
1756-8919
Publication state
Published
Issued date
2011
Volume
3
Number
8
Pages
995-1010
Language
english
Abstract
In the last few years, a need to account for molecular flexibility in drug-design methodologies has emerged, even if the dynamic behavior of molecular properties is seldom made explicit. For a flexible molecule, it is indeed possible to compute different values for a given conformation-dependent property and the ensemble of such values defines a property space that can be used to describe its molecular variability; a most representative case is the lipophilicity space. In this review, a number of applications of lipophilicity space and other property spaces are presented, showing that this concept can be fruitfully exploited: to investigate the constraints exerted by media of different levels of structural organization, to examine processes of molecular recognition and binding at an atomic level, to derive informative descriptors to be included in quantitative structure--activity relationships and to analyze protein simulations extracting the relevant information. Much molecular information is neglected in the descriptors used by medicinal chemists, while the concept of property space can fill this gap by accounting for the often-disregarded dynamic behavior of both small ligands and biomacromolecules. Property space also introduces some innovative concepts such as molecular sensitivity and plasticity, which appear best suited to explore the ability of a molecule to adapt itself to the environment variously modulating its property and conformational profiles. Globally, such concepts can enhance our understanding of biological phenomena providing fruitful descriptors in drug-design and pharmaceutical sciences.
Keywords
, FREE AMINO-ACIDS, SOLVENT CONSTRAINTS, MUSCARINIC RECEPTORS, PROTEIN FLEXIBILITY, INFORMATION-CONTENT, SIDE-CHAINS, DRUG DESIGN, LIPOPHILICITY, DYNAMICS, ACETYLCHOLINE
Pubmed
Web of science
Create date
23/09/2011 16:04
Last modification date
20/08/2019 16:42
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