96
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.
