We explore the means by which immobilization of a substrate on a surface can increase the rate of a diffusion-controlled enzymatic reaction. A quasichemical approach is developed and compared with Brownian dynamics simulations. We use these methods to show that restricting only the orientation of the enzyme by long-range interactions with the surface is sufficient for enhancing catalysis.

Recently, we described a pathway analysis technique (paper 1) for analyzing generic schemes for single-molecule kinetics based upon the first-passage time distribution. Here, we employ this method to derive expressions for the Poisson indicator, a normalized measure of stochastic variation (essentially equivalent to the Fano factor and Mandel's Q parameter), for various renewal (i.e., memoryles...

We review recent evidence illustrating the fundamental difference between cytoplasmic and test tube biochemical kinetics and thermodynamics, and showing the breakdown of the law of mass action and power-law approximation in in vivo conditions. Simulations of biochemical reactions in non-homogeneous media show that as a result of anomalous diffusion and mixing of the biochemical species, reactio...

Dynamical system models of complex biochemical reaction networks are usually high-dimensional, non-linear, and contain many unknown parameters. In some cases the reaction network structure dictates that positive equilibria must be unique for all values of the parameters in the model. In other cases multiple equilibria exist if and only if special relationships between these parameters are satis...

Biochemical processes typically involve huge numbers of individual reversible steps, each with its own dynamical rate constants. For example, kinetic proofreading processes rely upon numerous sequential reactions in order to guarantee the precise construction of specific macromolecules. In this work, we study the transient properties of such systems and fully characterize their first passage (c...

The multi-level method for discrete-state systems, first introduced by Anderson and Higham (SIAM Multiscale Model Simul 10(1):146-179, 2012), is a highly efficient simulation technique that can be used to elucidate statistical characteristics of biochemical reaction networks. A single point estimator is produced in a cost-effective manner by combining a number of estimators of differing accurac...

In biochemical networks, reactions often occur on disparate timescales and can be characterized as either fast or slow. The quasi-steady-state approximation (QSSA) utilizes timescale separation to project models of biochemical networks onto lower-dimensional slow manifolds. As a result, fast elementary reactions are not modeled explicitly, and their effect is captured by nonelementary reaction-...

Introduction Conclusions References

In many biochemical processes, proteins bound to DNA at distant sites are brought into close proximity by loops in the underlying DNA. For example, the function of some gene-regulatory proteins depends on such 'DNA looping' interactions. We present a new technique for characterizing the kinetics of loop formation in vitro, as observed using the tethered particle method, and apply it to experime...

Switch like responses appear as common strategies in the regulation of cellular systems. Here we present a method to characterize bistable regimes in biochemical reaction networks that can be of use to both direct and reverse engineering of biological switches. In the design of a synthetic biological switch, it is important to study the capability for bistability of the underlying biochemical n...