Rebinding in biochemical reactions on membranes

Area of Science:

• Biochemistry
• Chemical Kinetics
• Computational Biology

Background:

• Rebinding of dissociated molecules is critical for biochemical processes, especially multisite protein modification.
• Spatio-temporal correlations necessitate spatial models, but ODE models can incorporate rebinding in 3D by adding reaction network connections.
• The rate constants for these connections depend on the rebinding probability.

Purpose of the Study:

• Derive an explicit formula for rebinding probability in two space dimensions (2D) for biochemical reactions on membranes.
• Enable ordinary differential equation (ODE) models to accurately replicate detailed stochastic spatial simulations for membrane reactions.
• Investigate the role of rebinding in ultrasensitivity for multisite modification of membrane-bound proteins.

Main Methods:

• Derivation of an explicit formula for rebinding probability in 2D.
• Comparison of ODE model predictions using the derived formula against detailed stochastic spatial simulations.
• Computation of a new concentration-dependent rebinding probability for reactions in three space dimensions (3D).

Main Results:

• An explicit formula for rebinding probability in 2D biochemical reactions was derived.
• ODE models utilizing this formula successfully replicated stochastic spatial simulations.
• The formula predicts ultrasensitivity in multisite modification of membrane proteins.
• A new concentration-dependent rebinding probability for 3D reactions was computed.

Conclusions:

• The derived 2D rebinding probability formula enhances ODE models for membrane biochemistry.
• Rebinding plays a significantly larger role in membrane reactions than in cytoplasmic reactions.
• The findings have implications for understanding ultrasensitivity in membrane-bound protein modification.