@article {393, title = {Long-Range Conductivity in Proteins Mediated by Aromatic Residues}, journal = {ACS Physical Chemistry Au}, volume = {3}, year = {2023}, month = {09}, pages = {444{\textendash}455}, abstract = {

Single-molecule measurements show that many proteins, lacking any redox cofactors, nonetheless exhibit electrical conductance on the order of a nanosiemen over 10 nm distances, implying that electrons can transit an entire protein in less than a nanosecond when subject to a potential difference of less than 1 V. This is puzzling because, for fast transport (i.e., a free energy barrier of zero), the hopping rate is determined by the reorganization energy of approximately 0.8 eV, and this sets the time scale of a single hop to at least 1 μs. Furthermore, the Fermi energies of typical metal electrodes are far removed from the energies required for sequential oxidation and reduction of the aromatic residues of the protein, which should further reduce the hopping current. Here, we combine all-atom molecular dynamics (MD) simulations of non-redox-active proteins (consensus tetratricopeptide repeats) with an electron transfer theory to demonstrate a molecular mechanism that can account for the unexpectedly fast electron transport. According to our MD simulations, the reorganization energy produced by the energy shift on charging (the Stokes shift) is close to the conventional value of 0.8 eV. However, the non-ergodic sampling of molecular configurations by the protein results in reaction-reorganization energies, extracted directly from the distribution of the electrostatic energy fluctuations, that are only \~{}0.2 eV, which is small enough to enable long-range conductivity, without invoking quantum coherent transport. Using the MD values of the reorganization energies, we calculate a current decay with distance that is in agreement with experiment.

}, doi = {10.1021/acsphyschemau.3c00017}, url = {https://doi.org/10.1021/acsphyschemau.3c00017}, author = {Krishnan, Siddharth and Aksimentiev, Aleksei and Lindsay, Stuart and Matyushov, Dmitry} } @article {380, title = {Leakless end-to-end transport of small molecules through micron-length DNA nanochannels}, journal = {Science Advances}, volume = {8}, year = {2022}, month = {09/09/2022}, abstract = {
Designed and engineered protein and DNA nanopores can be used to sense and characterize single molecules and control transmembrane transport of molecular species. However, designed biomolecular pores are less than 100 nm in length and are used primarily for transport across lipid membranes. Nanochannels that span longer distances could be used as conduits for molecules between nonadjacent compartments or cells. Here, we design micrometer-long, 7-nm-diameter DNA nanochannels that small molecules can traverse according to the laws of continuum diffusion. Binding DNA origami caps to channel ends eliminates transport and demonstrates that molecules diffuse from one channel end to the other rather than permeating through channel walls. These micrometer-length nanochannels can also grow, form interconnects, and interface with living cells. This work thus shows how to construct multifunctional, dynamic agents that control molecular transport, opening ways of studying intercellular signaling and modulating molecular transport between synthetic and living cells.
}, doi = {10.1126/sciadv.abq4834}, url = {https://www.science.org/doi/10.1126/sciadv.abq4834}, author = {Li, Yi and Maffeo, Christopher and Joshi, Himanshu and Aleksei Aksimentiev and M{\'e}nard, Brice and Schulman, Rebecca} } @article {237, title = {Large-Conductance Transmembrane Porin Made from DNA Origami}, journal = {ACS Nano}, volume = {10}, year = {2016}, month = {08/2016}, pages = {8207--8214}, abstract = {

DNA nanotechnology allows for the creation of three-dimensional structures at nanometer scale. Here, we use DNA to build the largest synthetic pore in a lipid membrane to date, approaching the dimensions of the nuclear pore complex and increasing the pore-area and the conductance tenfold compared to previous man-made channels. In our design, nineteen cholesterol-tags anchor a megadalton funnel-shaped DNA origami porin in a lipid bilayer membrane (see equilibration trajectory, require login to nanoHUB). Confocal imaging and ionic current recordings reveal spontaneous insertion of the DNA porin into the lipid membrane, creating a transmembrane pore of tens of nanosiemens conductance (see ionic current trajectory). All-atom molecular dynamics simulations characterize the conductance mechanism at the atomic level and independently confirm the DNA porins{\textquoteright} large ionic conductance.

}, doi = {10.1021/acsnano.6b03759}, author = {Kerstin G{\"o}pfrich* and Chen-Yu Li* and Maria Ricci and Satya Prathyusha Bhamidimarri and Jejoong Yoo and Bertalan Gyenes and Alexander Ohmann and Mathias Winterhalter and Aleksei Aksimentiev and Ulrich F Keyser} } @article {37, title = {Lipid bilayer coated Al(2)O(3) nanopore sensors: towards a hybrid biological solid-state nanopore}, journal = {Biomed Microdevices}, volume = {13}, year = {2011}, month = {2011 Aug}, pages = {671-82}, abstract = {

Solid-state nanopore sensors are highly versatile platforms for the rapid, label-free electrical detection and analysis of single molecules, applicable to next generation DNA sequencing. The versatility of this technology allows for both large scale device integration and interfacing with biological systems. Here we report on the development of a hybrid biological solid-state nanopore platform that incorporates a highly mobile lipid bilayer on a single solid-state Al(2)O(3) nanopore sensor, for the potential reconstitution of ion channels and biological nanopores. Such a system seeks to combine the superior electrical, thermal, and mechanical stability of Al(2)O(3) solid-state nanopores with the chemical specificity of biological nanopores. Bilayers on Al(2)O(3) exhibit higher diffusivity than those formed on TiO(2) and SiO(2) substrates, attributed to the presence of a thick hydration layer on Al(2)O(3), a key requirement to preserving the biological functionality of reconstituted membrane proteins. Molecular dynamics simulations demonstrate that the electrostatic repulsion between the dipole of the DOPC headgroup and the positively charged Al(2)O(3) surface may be responsible for the enhanced thickness of this hydration layer. Lipid bilayer coated Al(2)O(3) nanopore sensors exhibit excellent electrical properties and enhanced mechanical stability (GΩ seals for over 50 h), making this technology ideal for use in ion channel electrophysiology, the screening of ion channel active drugs and future integration with biological nanopores such as α-hemolysin and MspA for rapid single molecule DNA sequencing. This technology can find broad application in bio-nanotechnology.

}, keywords = {Aluminum Oxide, Biosensing Techniques, DNA, Fluorescence Recovery After Photobleaching, Ion Channels, Lipid Bilayers, Models, Biological, Molecular Dynamics Simulation, Nanopores, Nanotechnology, Phosphatidylcholines, Sequence Analysis, DNA, Silicon Dioxide, Staining and Labeling, Titanium}, issn = {1572-8781}, doi = {10.1007/s10544-011-9537-3}, author = {Venkatesan, Bala Murali and Polans, James and Jeffrey Comer and Sridhar, Supriya and Wendell, David and Aleksei Aksimentiev and Rashid Bashir} } @article {77, title = {Large scale simulation of protein mechanics and function}, journal = {Adv Protein Chem}, volume = {66}, year = {2003}, month = {2003}, pages = {195-247}, keywords = {Amino Acid Motifs, Aquaporins, Catalysis, Cell Membrane, Computer Simulation, Fibronectins, Hydrogen Bonding, Models, Molecular, Protein Conformation, Protein Denaturation, Protein Folding, Protein Structure, Secondary, Proteins, Proton-Translocating ATPases, Substrate Specificity, Time Factors, Water}, issn = {0065-3233}, author = {Tajkhorshid, Emad and Aleksei Aksimentiev and Ilya A Balabin and Gao, Mu and Isralewitz, Barry and Phillips, James C and Zhu, Fangqiang and Klaus Schulten} }