Protein translocation in narrow pores: influence of the pore dynamical fluctuations

We study the phenomena of translocation of a globular protein through a fluctuating cylindrical nanopore under the action of a driving force using the method of Langevin dynamics simulation (Go-like protein model). The work is motivated by recent experiments on voltage driven transport of protein across nano-channel. In the first part of the thesis we describe a numerical analysis on the driven transport of Maltose binding protein (MBP) across a nano-pore in the framework of coarse-grained modeling. The protein is described by a native centric model on a C carbon backbone to study the influence of protein-like structural properties on the translocation process. In this transport mechanism of protein across a channel, the force-fields consists of stretching energy, bending energy and torsion energy. The non-bonded interaction energy is modeled by Lennard-Jones potential. We model the fluctuating nanopore through which the protein is confined by a step-like soft-core repulsive potential with cylindrical symmetry which is set parallel the x -axis of the frame of reference to used for translocation simulations In chapter 3 we investigate the translocation of MBP through a static pore. We characterized the translocation mechanism by studying the thermodynamical and kinetic properties of the process. In particular, we study the average of translocation time, the mobility, and the translocation probability as a function of pulling force F acting in the channel. The translocation process depend on the free-energy barrier that protein has to overcome in order to move along the channel. Such a free-energy barrier occurs due to the conflict of the unfolding energy and the entropy connected with the confinement effects of the pore. Umbrella sampling simulation is implemented to compute the free-energy landscape as a function of reaction coordinate. To compute the translocation free-energy profile from the umbrella sampling simulation, we introduce an artificial harmonic biasing potential, forcing the system dynamics to explore the set of unstable conformations. The effect of the umbrella potential is than deweighted from the Boltzmann weight by processing the data through appropriate debiasing algorithms. We used the free-energy profile to built up a phenomenological one - dimensional drift - diffusion model in the reaction coordinate based on the Smoluchowski stochastic differential equation. The results obtained from the mathematical model are then used in comparison with molecular dynamics simulation to explains and reproduces the behavior of the translocation observables. In chapter 4 and 5, we study the effect of fluctuating environment in protein transport dynamics. In particular, we investigate the translocation of a protein across a temporally modulated nano-pore. We allow the radius of the cylindrical pore to oscillate harmonically with certain frequency and amplitude about an average radius. The protein is imported inside the pore whose dynamics is influences by the fluctuating nature of the pore. We investigate the dynamic and thermodynamical properties of the translocation process by revealing the statistics of translocation time as a function of the pulling inward force acting along the axis of the pore, and the frequency of the time dependent radius of the channel. We also examine the distribution of translocation time in the intermediate frequency regime. We observe that the shaking mechanism of pore leads to accelerate the translocation process as compared to the static channel that has a radius equal to the mean radius of oscillating pore. Moreover, the translocation time shows a global maximum as a function of frequency of the oscillating radius, hence revealing a resonant activation phenomenon in the dynamics of protein translocation