Molecules as complex adaptative systems: constrained molecular properties and their biochemical significance.

Détails

ID Serval
serval:BIB_14799
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Molecules as complex adaptative systems: constrained molecular properties and their biochemical significance.
Périodique
European Journal of Pharmaceutical Sciences
Auteur(s)
Testa B., Bojarski A.J.
ISSN
0928-0987 (Print)
ISSN-L
0928-0987
Statut éditorial
Publié
Date de publication
2000
Volume
11 Suppl 2
Pages
S3-14
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't ; Review
Publication Status: ppublish
Résumé
The first part of the paper describes molecular structure by considering form (geometrical structure), function (observable properties resulting from interaction with a probe) and fluctuation (dynamics). The fluctuation of form and function generates a number of molecular states, whose ensemble delineates a property space. This concept is central when examining the mutual interactions of a chemical compound with its molecular environment. Because of these interactions, a chemical compound and its molecular environment may form a complex system in its own right, which exhibits emergent properties (e.g., solubility and lipophilicity) that are non-existent (and meaningless) at the level of description of isolated molecules, and which are part of the property space of the compound. The emergence of these properties is accompanied by constraints on the property space of the constituents, and especially of the chemical compound. Some of these constraints are well known, e.g., conformational shifts as seen in induced fit and chameleonic behaviour. Such mutual adaptability between a compound and its environment is a fundamental but insufficiently recognized phenomenon in biochemistry, since it amplifies molecular complementarity and hence molecular recognition. In the second part of this paper, the results of an exploratory study are reported which show that contraints on the property space of constituents also occur when molecules are covalently incorporated into larger compounds. Using the GRID/VolSurf softwares, we bring evidence that when some amino acids become residues in peptides, they experience a modest increase in their polarity and a marked increase in their hydrophobicity (as assessed by their polarity field and hydrophobicity field, respectively). The biological and pharmacological implications of constraints on solutes, ligands and monomers could inspire new directions of research.
Mots-clé
Amino Acids/chemistry, Models, Molecular, Molecular Structure, Receptors, Drug/chemistry, Receptors, Drug/metabolism, Structure-Activity Relationship
Pubmed
Création de la notice
19/11/2007 10:35
Dernière modification de la notice
20/08/2019 13:43
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