Modeling of Biomolecular Systems Interactions, Dynamics, and Allostery: Bridging Experiments and Computations - September 10-14, 2014, Istanbul, Turkey

Modeling of Biomolecular Systems Interactions, Dynamics, and Allostery Poster Session I

43-POS Board 43 Electrostatic Denaturation of Proteins during Solid-State Nanopore Translocation Mohammad R. Hasan 1,2 , Mohammed Arif I. Mahmood 1,2 , Adnan Ashfaq 4 , Samir M. Iqbal 1,2,3 . 2 Electrical Engineering, University of Texas at Arlington, Arlington, TX, USA, 3 Bioengineering, University of Texas at Arlington, Arlington, TX, USA, 4 Mechanical and Aerospace Engineering, University of Texas at Arlington, Arlington, TX, USA. 1 Nano-Bio Lab, University of Texas at Arlington, Arlington, TX, USA, Protein translocation through solid-sate nanopores is promising emerging technique for identification of specific molecules at low concentrations. In the experiments, a voltage bias is applied across the nanopore and the ionic current is measured through the nanopore. As soon as a molecule travels through the nanopore, a dip in current is registered, called a pulse. The interactions in the confinements of a nanopore and biological molecules are still less understood. Experimental work at such scales is extremely difficult and the results are statistical in nature. Molecular dynamics simulations can predict important parameters to achieve required sensitivity and selectivity in detecting proteins. We report Nanoscale Molecular Dynamics simulations performing all-atom physical interactions between the nanopore walls and the proteins along with externally applied forces. The potential across the 6 nm thick nanopore was varied gradually from 50 to 500 mV and the conformational changes were investigated temporally for 10 ns of simulation time. The deviation of the protein structure from its initial form was quantified with root mean square deviations and also from changes in the energy states of the system. The otherwise stable protein structures were seen to be enormously disrupted, probably loosing functionalities also. The gradual unfolding of the protein molecules was observed both at the nanopore opening and inside the pore. The protein size, molecular weight and amino acid chain length also affected the conformational variation. Such changes can affect the outputs in proteomic studies at hand, by large margin, as any elongation or unfolding in the structure can change the supposedly “signature pulses” of the molecules. These results add towards better understanding of the protein behavior when passing through the nanopore and thus assisting its detection. Theoretical assessment of these phenomena is crucial before drawing experimental conclusions.

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