A general model of multivalent binding with ligands of heterotypic subunits and multiple surface receptors

Tan, Z. C.; Meyer, A. S.

doi:10.1101/2021.03.10.434776

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bioRxiv · 10.1101/2021.03.10.434776

A general model of multivalent binding with ligands of heterotypic subunits and multiple surface receptors

Tan, Z. C.·Meyer, A. S.

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Abstract

Multivalent cell surface receptor binding is a ubiquitous biological phenomenon with functional and therapeutic significance. Predicting the amount of ligand binding for a cell remains an important question in computational biology as it can provide great insight into cell-to-cell communication and rational drug design toward specific targets. In this study, we extend a mechanistic, two-step multivalent binding model. This model predicts the behavior of a mixture of different multivalent ligand complexes binding to cells expressing various types of receptors. It accounts for the combinatorially large number of interactions between multiple ligands and receptors, optionally allowing a mixture of complexes with different valencies and complexes that contain heterogeneous ligand units. We derive the macroscopic predictions and demonstrate how this model enables large-scale predictions on mixture binding and the binding space of a ligand. This model thus provides an elegant and computationally efficient framework for analyzing multivalent binding.

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Tan, Z. C., Meyer, A. S.. 2021-03-11. A general model of multivalent binding with ligands of heterotypic subunits and multiple surface receptors. https://doi.org/10.1101/2021.03.10.434776

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