DBP4: Biosensors. DNA passing through a nanopore (all-atom MD simulation) Diamond thin films as tethering surfaces for bacterial capture

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1 8 DBP4: Biosensors Biomedical relevance Significance and challenges Biosensors provide unique ways to investigate and monitor the health of a living body. Computational microscope can image nanodevices in watery environments. Biosensors are integral elements to the development of systems for personalized genomics (Oxford Nanopore systems, Illumina). Nanopores are a versatile research tool for detecting and manipulating single molecules. Modeling biosensors requires an ability to simulate mixtures of inorganic and organic materials, e.g. Si DNA H2O for DNA translocation through a solid-state nanopore. DNA passing through a nanopore (all-atom MD simulation) Diamond thin films as tethering surfaces for bacterial capture R. Bashir et al., Adv. Funct. Mater, 2011, 21 BTRC has over 40 publications with 700 citations in the area.

2 9 Collaborators Sequencing DNA using the biological nanopore MspA. Jens Gundlach Professor of Physics, U. of Washington Increasing fidelity of solid-state nanopore sensors Rashid Bashir Professor of ECE, UIUC (3 joint publications) Greg Timp Professor of ECE, Notre Dame (13 joint publications) Meni Wanunu Asst. Professor of Physics, Northeastern U. (1 joint publication) Nanodevice for kinase detection New! Logan Liu Asst. Professor of ECE, UIUC (1 joint publication submitted) BTRC for MacromolecularOxford Modeling and Bioinformatics Systems Technological application: Nanopore

3 Oxford Nanopore Technologies 10 BTRC project to be funded by Oxford Nanopore MinION MinION: a disposable DNA sequencing device the size of a USB memory stick whose low cost, portability and ease of use are designed to make DNA sequencing universally accessible. A single MinION is expected to retail at less than $900. A typical setup to sequence DNA using α- hemolysin MinION will allow Novel method of DNA 'strand sequencing' that uses an array of proprietary protein nanopores. A complete human genome can be deciphered using 8,000 nanopores in 15 minutes.

4 Recent progress: solid-state nanopores 11 Slowing DNA translocation in LiCl Kowalczyk et al., Nano Lett., 2012, 12 (2), pp Collaboration with Dekker (TU Delft) Nanopore Analysis of RNA/Antibiotic Complexes Wanunu et al., ACS Nano., 2011, 5 (12), pp Collaboration with Meni Wanunu (Northeastern U.) = q Replacing KCl LiCl gives 10x slowdown in DNA translocation without sacrificing ionic current signal! q MD simulations revealed that strong Li H 2 0 DNA bonds were the microscopic mechanism responsible q Required re-parametrization of ion-dna interactions* * J. Yoo and A. Aksimentiev, JPCL, 2012, 3 (1), pp A-site construct Paromomycin MD simulations revealed a relationship between the ionic current and complexation of paromomycin with A-site construct. I (na) M KCl 500 pa Added RNA constructs 1 ms 1 +1 µm A-site 2 Time (s) Permeation of RNA molecules indicated by current blockade spikes 3 4

5 TR&D Connections and Challenges 14 TR&D1 NAMD Free energy support Brownian Dynamics support User defined forces performance Fluctuating charge polarizability TR&D2 VMD Improved coarse grained modeling Multi-scale surface representation Support for opensystem simulations Collective variables tool TR&D3 Brownian Mover BDGRATOR DIFFUMAP HYDROBD OSVIEW Legend: Completed Under development Nanochannel Microchannel Atoms-to-microns model for small solute transport through sticky nanochannels, R. Carr, J. Comer, M. Ginsberg, A. Aksimentiev, Lab on a Chip, 2011, 11,