ArticleProceedings of the National Academy of Sciences of the United States of America1993
Probability model for molecular recognition in biological receptor repertoires: significance to the olfactory system.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1993. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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42 citing papers in PubMed, 164 citations in OpenAlex.
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- Twenty Years of "Lipid World": A Fertile Partnership with David Deamer.Life (Basel, Switzerland) · 2019Review
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- Structured Odorant Response Patterns across a Complete Olfactory Receptor Neuron Population.Neuron · 2019Article
- Systems protobiology: origin of life in lipid catalytic networks.Journal of the Royal Society, Interface · 2018Review
- Intrinsic limits to gene regulation by global crosstalk.Nature communications · 2016Article
- Receptor arrays optimized for natural odor statistics.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Hierarchy and extremes in selections from pools of randomized proteins.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- The universal statistical distributions of the affinity, equilibrium constants, kinetics and specificity in biomolecular recognition.PLoS computational biology · 2015Article
- Prospective identification of parasitic sequences in phage display screens.Nucleic acids research · 2014Article
- In vitro selection of proteins with desired characteristics using mRNA-display.Methods (San Diego, Calif.) · 2013Article
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- Degeneracy allows for both apparent homogeneity and diversification in populations.Bio Systems · 2012Article
- Personal receptor repertoires: olfaction as a model.BMC genomics · 2012Article
- A model of non-elemental olfactory learning in Drosophila.Journal of computational neuroscience · 2012Article
- Article
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3 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
A generalized phenomenological model is presented for stereospecific recognition between biological receptors and their ligands. We ask what is the distribution of binding constants psi(K) between an arbitrary ligand and members of a large receptor repertoire, such as immunoglobulins or olfactory receptors. For binding surfaces with B potential subsite and S different types of subsite configurations, the number of successful elementary interactions obeys a binomial distribution. The discrete probability function psi(K) is then derived with assumptions on alpha, the free energy contribution per elementary interaction. The functional form of psi(K) may be universal, although the parameter values could vary for different ligand types. An estimate of the parameter values of psi(K) for iodovanillin, an analog of odorants and immunological haptens, is obtained by equilibrium dialysis experiments with nonimmune antibodies. Based on a simple relationship, predicted by the model, between the size of a receptor repertoire and its average maximal affinity toward an arbitrary ligand, the size of the olfactory receptor repertoire (Nolf) is calculated as 300-1000, in very good agreement with recent molecular biological studies. A very similar estimate, Nolf = 500, is independently derived by relating a theoretical distribution of maxima for psi(K) with published human olfactory threshold variations. The present model also has implications to the question of olfactory coding and to the analysis of specific anosmias, genetic deficits in perceiving particular odorants. More generally, the proposed model provides a better understanding of ligand specificity in biological receptors and could help in understanding their evolution.
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