Conformationally gated rate processes in biological macromolecules

The concept of gating has been applied to the theoretical description of rate processes coupled to conformational rearrangements of biological macromolecules both out of equilibrium and near equilibrium. The out-of-equilibrium rearrangements are discussed in terms of requirements imposed by the complexity of biomolecules. These include (i) a variety of relaxation time scales for different degrees of freedom, (ii) constraints arising from their interactions, and (iii) the hierarchy of conformational substates. The simplest possible model that satisfies the requirements i-iii is developed. The model suggests that the motion along the reaction coordinate is gated by slower degrees of freedom. We show that under this assumption dynamics of the reaction coordinate resembles anomalous (non-Gaussian) diffusion. Expressions for observables derived within our model predict (i) a suppression of reaction coordinate dynamics in biomolecules imbedded in rigid matrixes, (ii) a transition from the familiar Debye exponential relaxation to the Kohlrausch-Williams-Watts relaxation described by a stretched exponential, and (iii) distinct temperature dependencies of relaxation rates for these relaxation processes. The experimental data on ligand binding to myoglobin support predictions i and ii. Coupling of rate processes to local conformational rearrangements near equilibrium has also been studied. As a particular example of such processes, we consider hole injection and transport in DNA molecular wires. Our treatment suggests that fluctuations in the mutual arrangement of base pairs in the stack can serves as a gate for both processes. This explains the unusual temperature dependence of the voltage gap found experimentally for poly(guanine)-poly(cytosine) molecular wires. The diffusion coefficient of holes and their mobility as a function of temperature are estimated for base pair stacks of varying structure.