Many proteins exhibit multiple binding patches. A patch may harbour a key chemical modification site, but may also simply act as a trap for the binding to another site. Here we consider the scenario in which one molecule (enzyme) binds another molecule (substrate) which contains two sites. We present microscopic expressions for the rate at which the enzyme binds to a particular site on the substrate, both for the scenario in which the enzyme directly binds the site without first visiting the other site, and for the case in which it may visit the other site an arbitrary number of times before binding to the site of interest. We also present the expressions for the corresponding dissociation reactions. These expressions can be used to compute in a single rare-event simulation of the dissociation pathway not only both the intrinsic and effective dissociation rate constants but also both association rate constants.

Taylor & Francis
The Netherlands Organisation for Scientific Research (NWO)
Molecular Physics
Biochemical Networks

Vijaykumar, A., ten Wolde, P. R., & Bolhuis, P. (2018). Generalised expressions for the association and dissociation rate constants of molecules with multiple binding sites. Molecular Physics, 116(21-22), 3042–3054. doi:10.1080/00268976.2018.1473653