Uncovering the Classification Characteristics of Olfactory G Protein-Coupled Receptors

The human sense of smell is made possible through the use of the so-called olfactory receptors. These receptors are proteins which are embedded into the cellular membranes located in the nose. The olfactory receptors are members of the G protein-coupled receptors (GPCRs) class. The function of a GPCR is to transmit a signal into the cell structure when a molecule binds to the GPCR on the outside of the cellular membrane. The olfactory receptors are mostly found inside the nose. However a number of these receptors are also found on other locations. For this reason the olfactory receptors may also be involved in functions other than making the sense of smell possible. Generally speaking, GPCRs are already essential in drug discovery. Because of this the pharmacological importance to map the hidden function of the olfactory receptors may introduce new drug targets. The paper by Samsonova et al. proposed a rule-based characterisation method for classifying olfactory receptors using multiple sequence alignment (MSA). In a MSA the olfactory receptor sequences can be compared with each other. This thesis continues the effort of finding characteristic amino acid combinations in olfactory GPCRs. Two existing rule discovery algorithms, PRISM and Tertius, are used in combination with two optimisation methods, rule set optimisation and rule subset generation. The combined methods found highly supported rule sets which classify the olfactory receptor class very successfully. Moreover these rule sets cover multiple highly characteristic features in a non-sequential manner throughout the transmembrane (TM) domains of the olfactory receptors. In contrast with the well known motifs, which uses sequences of conserved amino acids in chronological order to classify a receptor class. The used characterisation methods in this thesis could be used to examine the characteristics of other GPCRs. Furthermore these method could use other alignment methods such as a structural alignment. This could uncover important characterisations within the 3D structure which may lead to a better understanding of the functions of the olfactory receptor.