The utilization of multiple post translational modifications (PTMs) in regulating a biological response is ubiquitous in cell signaling. If each PTM contributes an additional, equivalent binding site, then one consequence of an increase in the number of PTMs may be to increase the probability that, upon disassociation, a ligand immediately rebinds to its receptor. How such effects may influence cell signaling systems has been less studied. Here, a self-consistent integral equation formalism for ligand rebinding in conjunction with Monte Carlo simulations are employed to further investigate the effects of multiple, equivalent binding sites on shaping biological responses. Multiple regimes that characterize qualitatively different physics due to the differential prevalence of rebinding effects and their relation to systems-level properties are predicted and studied. Calculations suggest that when ligand rebinding contributes significantly to the dose response, a purely allovalent model can influence the binding curves nonlinearly but other mechanistic ingredients are required to achieve high degrees of biochemical cooperativity. It is our hope that these calculations motivate experiments that can further unravel the many functional consequences of multi-site phosphorylation.
the paper is withdrawn for the moment
R
The utilization of multiple post translational modifications (PTMs) in regulating a biological response is ubiquitous in cell signaling. If each PTM contributes an additional, equivalent binding site, then one consequence of an increase in the number of PTMs may be to increase the probability that, upon disassociation, a ligand immediately rebinds to its receptor. How such effects may influence cell signaling systems has been less studied. Here, a self-consistent integral equation formalism for ligand rebinding in conjunction with Monte Carlo simulations are employed to further investigate the effects of multiple, equivalent binding sites on shaping biological responses. Multiple regimes that characterize qualitatively different physics due to the differential prevalence of rebinding effects and their relation to systems-level properties are predicted and studied. Calculations suggest that when ligand rebinding contributes significantly to the dose response, a purely allovalent model can influence the binding curves nonlinearly but other mechanistic ingredients are required to achieve high degrees of biochemical cooperativity. It is our hope that these calculations motivate experiments that can further unravel the many functional consequences of multi-site phosphorylation.
the paper is withdrawn for the moment