Molecules and Meaning:
How Do Molecules Become Biochemical Signals?

Bernard Testa1, Lemont B. Kier2 and Andrzej J. Bojarski3


1) Institute of Medicinal Chemistry, School of Pharmacy, University of Lausanne, CH-1015 Lausanne, Switzerland, <Bernard.Testa @ ICT.UNIL.CH>

2) Center for the Study of Biological Complexity, Virginia Commonwealth University¸ Richmond, VA 23298, USA, <>

3) Department of Medicinal Chemistry, Institute of Pharmacology of the Polish Academy of Sciences, 12 Smetna St., PL-31343 Krakow, Poland,


ŠThis paper is not for reproduction, even partial, without the express permission of the first author.


The objective of this paper is to reflect on how molecules can acquire macroscopic meaning (i.e., carry a message to macroscopic levels) in a context of biological evolution. First, the structure of molecules is explained in terms of form (molecular geometry), function (measurable or computable molecular properties), and fluctuation. Fluctuations in form and function create distinct molecular states, and the ensemble of all molecular states defines a molecular space (also known as a property space).

The second part examines molecules in a chemical context. The interplay between a chemical compound and its environment creates a complex system in its own right, as exemplified by solutions. A solute influences the solvent by affecting its organization and some colligative properties, while the solvent often has a marked influence on the solute by constraining its property space and so selecting some of its molecular states. Solutions may display emergent properties not existing in the separate components, e.g. chemical reactivity, implying that information has been created upon formation of the complex system.

The third part of the paper discusses the interaction of chemical compounds with biological media. In contrast to abiotic environments such as solvents whose degree of organization is comparatively low, biological media are characterized by a high degree of organization. Examples at the macromolecular level include functional proteins (receptors, enzymes, transporters, ...) or nucleic acids. When a molecule is recognized by such a macromolecule and interacts (binds) productively with it, a complex system is produced whose emergent property is the functional response, and which strongly constrains both of its components. The chemical is frozen into a single or a very limited number of molecular states (induced fit), whereas the macromolecule is activated by a conformational change (e.g. an allosteric effect). Here again, emergent information appears in the complex. However, there is an essential difference with abiotic systems since the emergent information can now be translated into a functional biochemical reaction that in turn will be amplified into a macroscopic biological response. In other words, information emerging in the molecule-macromolecule complex is a signal that becomes meaning as it is recognized in the higher hierarchy of nested biological contexts.

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