ERA-Chemistry: Design and synthesis of biologically inspired ion-conducting nanopores

• Applicant: Professor Dr. Paolo Carloni
• Subject Area: Theoretical Chemistry: Electronic Structure, Dynamics, Simulation ; Biological and Biomimetic Chemistry
• Term: from 2014 to 2016
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 252093367

Artificial nanopores are crucial components for emerging nanodevices such as high-throughput DNA sequencers. They function under concentration and voltage gradients, but generic issues such as selectivity and rectification under these conditions are poorly understood. Computational means to simulate these non-equilibrium conditions are still limited. Here we will carry out novel steady-state non-equilibrium simulations (including diverse techniques such as Langevin Dynamics, Dynamic Monte Carlo, and Local Equilibrium Monte Carlo) of Na+ channel-inspired nanopores under the same conditions as experiment. These conditions include electrodes at fixed voltages and baths of fixed electrolyte concentrations. These boundary conditions provide the driving force for the steady state transport. First, we will focus on the bacterial NavMs channel in the open state, for which experimental structural information is available. Simulations of the wild-type protein and of mutants will be complemented by all-atom Molecular Dynamics calculations. The findings of the simulations will be tested against experiments performed by our collaborator Prof. C. Fahlke (Forschungszentrum Jülich, Germany). This proposal extends a toolkit previously developed by us and others to construct coarse-grained (CG) models of channels and membranes. A CG model of the wild-type and mutant NavMs channel will be designed and simulated.The most promising mutants in terms of selectivity of potassium against sodium (and also of monovalent against divalent) and voltage response will be used to propose artificial nanopore designs. Voltage response includes rectification and control of current between two electrodes by the voltage applied at a third electrode. Nanopores designs will be tested by simulations of CG models and will be constructed and tested by our experimental collaborator Z. Siwy (U. of California at Irvine, US).

• DFG Programme: Research Grants
• International Connection: Hungary, USA
• Partner Organisation: OTKA Hungarian Scientific Research Fund
• Participating Persons: Professor Dr. Dezso Boda; Professor Dr. Christoph Fahlke; Professorin Dr. Zuzanna Siwy