Arising through multiple binding elements, multivalency can specify the avidity, duration,
cooperativity, and selectivity of biomolecular interactions, but quantitative prediction
and design of these properties has remained challenging. Here we present MVsim , an
application suite built around a configurational network model of multivalency to
facilitate the quantification, design, and mechanistic evaluation of multivalent binding
phenomena through a simple graphical user interface. To demonstrate the utility and
versatility of MVsim , we first show that both monospecific and multispecific multivalent
ligand-receptor interactions, with their noncanonical binding kinetics, can be accurately
simulated. Further, to illustrate the conceptual insights into multivalent systems
that MVsim can provide, we apply it to quantitatively predict the ultrasensitivity
and performance of multivalent-encoded protein logic gates, evaluate the inherent
programmability of multispecificity for selective receptor targeting, and extract
rate constants of conformational switching for the SARS-CoV-2 spike protein and model
its binding to ACE2 as well as multivalent inhibitors of this interaction. MVsim and
instructional tutorials are freely available at https://sarkarlab.github.io/MVsim/
.