A microscopic model of signal transduction mechanisms: olfaction

This thesis recognizes that: in many systems the initial small molecule - receptor recognition processes, and thus signal transduction, is not fully understood to the highest level of scientifc explanation and prediction. One such example of this is olfaction. Molecules cannot necessarily be predicted from a smell, and similarly a smell from molecules. Better understanding of these initial steps, would have important repercussions, especially in the field of rational drug design. So in general the thesis proves the physical feasibility and potential of a novel and generic signaling model, and in particular looks at those processes in olfaction. The conjecture 'Could humans recognize odours through phonon assisted tunneling?' is tested. This is based on the idea (Turin, 1996) that the nose recognizes an odorant's vibrations (phonons) via inelastic electron tunneling (IETS). The nose thus acts as a 'meat spectroscope'. First the background biology of the olfactory system is evaluated, then the conjecture is posed as a soluble problem. Traditional physics ideas are reconciled with the biological environment. It is proven that no physics based objections hold against the working of this new mechanism, thus a predictive and explanatory theory is now introduced to the field. The parameters of odorant discrimination are explored. In particular the 'Huang-Rhys factor' is modeled as a measure of the electron-phonon coupling integral to signal transduction. Several approaches are considered, 'odorant spectra' is created. Objections to the conjecture are considered, in particular the apparent paradox of enantiomer discrimination. The apparent paradox is shown to be obsolete. A correlation between a certain type of flexibility and whether enantiomer pairs smell the same is found. A rule is established: The members of an enantiomer pair will smell alike (type 1) when the molecules are rigid, and will smell different (type 2) when they are flexible. This flexibility refers to a particular property of six-membered rings. A consequence of this finding leads to the investigation of certain steroids in correlation to their bio-effects, and it is found that similar features are apparent, thus the mechanism of biological IETS is applied to other systems.

Level dc:type.qualificationlevel

Doctoral

Grantor dc:publisher.institution

UCL (University College London)

Year dc:date.issued

2009

Author dc:creator

• Brookes, J.C.

• Department of Physics and Astronomy

Language dc:language

en, eng