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arXiv · 2201.09471

Derangement model of ligand-receptor binding

Mobolaji Williams
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Abstract

We introduce a derangement model of ligand-receptor binding that allows us to quantitatively frame the question "How can ligands seek out and bind to their optimal receptor sites in a sea of other competing ligands and suboptimal receptor sites?" To answer the question, we first derive a formula to count the number of partial generalized derangements in a list, thus extending the derangement result of Gillis and Even. We then compute the general partition function for the ligand-receptor system and derive the equilibrium expressions for the average number of bound ligands and the average number of optimally bound ligands. A visual model of squares assembling onto a grid allows us to easily identify fully optimal bound states. Equilibrium simulations of the system reveal its extremes to be one of two types, qualitatively distinguished by whether optimal ligand-receptor binding is the dominant form of binding at all temperatures and quantitatively distinguished by the relative values of two critical temperatures. One of those system types (termed "search-limited," as it was in previous work) does not exhibit kinetic traps and we thus infer that biomolecular systems where optimal ligand-receptor binding is functionally important are likely to be search-limited.

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Mobolaji Williams. 2022-08-23. Derangement model of ligand-receptor binding. https://doi.org/10.1515/cmb-2022-0137

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