Greg Conradi Smith

Greg Conradi Smith

biology as a mathematical science, science among the liberal arts

Receptor Oligomers

Cell surface receptors detect chemical signals outside a cell and translate them into intracellular responses. Many important receptors are not single independent switches, but multi-subunit molecular machines whose parts interact with one another. Mathematical models are therefore essential for understanding how receptor structure, ligand binding, subunit state, and allosteric coupling shape cell behavior.

Our work develops mathematical and biophysical theory for receptor oligomers, with an emphasis on how receptor function emerges from protein subunits and the energetic interactions between them. This provides a framework for interpreting natural cell signaling and for building quantitative models that may inform pharmacology and drug development.

Cycle Representations

The lab’s work on cycle bases of product graphs gives a systematic way to enumerate conformational coupling in receptor dimers and higher-order oligomers. Starting from a hypothesized monomer state-transition diagram, the product-graph formalism helps identify the thermodynamic constraints that appear in the oligomer and gives each allosteric parameter a physical interpretation.

Current work extends this framework to receptor complexes, including dimeric G-protein-coupled receptors and receptor tyrosine kinases. Software for receptor oligomer analysis is being developed for quantitative pharmacologists and other life scientists, with longer-term interest in non-equilibrium phenomena such as nucleotide exchange.

Publications

  • Conradi Smith GD. Allostery in oligomeric receptor models. Mathematical Medicine and Biology: A Journal of the IMA 37:313-333, 2020. [10.1093/imammb/dqz016] [BioRxiv preprint]
  • Hammack RH and Smith GD. Cycle bases of reduced powers of graphs. ARS Mathematica Contemporanea 12(1):183-203, 2017. [journal] [arXiv preprint]

Funding

National Science Foundation, Division of Mathematical Sciences, Mathematical Biology. Cycle representations of receptor complex signal transduction. PI: Gregory D. Conradi Smith. NSF DMS-1951646, 6/20-5/23.