Comparative and statistical analysis of nAChR sequences: An <Emphasis Type="Italic">ab initio</Emphasis> approach to the origin of molecular discrimination |
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Authors: | YanLi Wang Zhong Li XuHong Qian |
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Institution: | Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China |
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Abstract: | Compared with traditional structure-based approaches for the identification of species-specific ligands, the ab initio approach, based on large-scale protein sequences from different species, has been used to locate specific sites that may
be important to the molecular selectivity of species. Statistically significant differences in the distribution of residues
in different species and differences in the physicochemical properties of residue-specific sites may largely account for species
selectivity. The nicotinic acetylcholine receptor (nAChR), an important neuro-receptor with significantly different ligand
selectivity in different species, was used to test our method. Because of the lack of nAChR structural information, the mechanism
of ligand discrimination is unclear which hinders attempts at novel molecular design. In this study, the specific site residues
186 and 189 in the principal subunits and residues 34, 55, 56, 57, 106 and 112 in complementary subunits of nAChR were identified
by applying our method with stringent statistical cutoffs. These sites were predicted to contribute to ligand selectivity
and this result coincides well with the known experimental data. |
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Keywords: | bioinformatics molecular discrimination nAChR statistical analysis species selectivity |
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