Theoretical Insights into Mechanisms of Stochastic Gating in Channel-Facilitated Molecular Transport

Abstract: Molecular motion through pores plays a crucial role in various natural and industrial processes. One of the most fascinating features of biological channel-facilitated transport is a stochastic gating process, when the channels dynamically fluctuate between several conformations during the translocation. Although this phenomenon has been intensively investigated, many properties of translocation in dynamically changing environment remain not well understood microscopically. We developed a discrete-state stochastic framework to analyze the molecular mechanisms of transport processes with stochastic gating by explicitly calculating molecular fluxes through the pores. Two scenarios are specifically investigated: 1) symmetry preserving stochastic gating with free-energy changes, and 2) stochastic gating with symmetry changes but without modifications in the overall particle-pore interactions. It is found that stochastic gating can both accelerate or slow down the molecular translocation depending on the specific parameters of the system. We argue that biological systems might optimize their performance by utilizing conformational fluctuations of channels. Our theoretical analysis clarifies physical-chemical aspects of the molecular mechanisms of transport with stochastic gating.