Cooperations: Prof. Mathias Winterhalter, Prof. Roland Benz and their groups
Funding: Deutsche Forschungsgemeinschaft
Nanopores and channels are ubiquitous in biological systems. They are responsible for the transport of various ions and substrates between the different compartments of biological systems separated by membranes. As an experimental method, electrophysiology has proven to be an important nano-analytical tool for the study of substrate transport through nanopores utilizing ion current measurements as a probe for the detection. An important example is the study of antibiotics translocation through porins such as the outer membrane protein F (OmpF) and C (OmpC). By now, numerical simulations have established themselves as an indispensable tool to decipher ion transport processes through biological as well as artificial nanopores.
Temperature dependent ion conductance in nanopores are being measured in a wide range of electrolyte concentrations in the Winterhalter and the Benz groups and compared to molecular dynamics simulations performed in our group. It is not only the aim to understand the electrostatic and steric effects playing the major role in the channel, but also to modify the channel by mutating certain amino acids in order to fulfill some predefined properties. This way, the conductance and the selectivity for certain ion types can be engineered and one can design, for example, a molecular sieve.
 J. Wang, P. Jigneshkumar Dahyabhai, U. Kleinekathöfer and M. Winterhalter, Dynamic Interaction of Fluoroquinolone with Magnesium Ions Monitored by Bacterial Outer Membrane Nanopores, Chem. Sci. 11, 10 344–10 353 (2020).
 J. D. Prajapati, C. Mele, M. A. Aksoyoglu, M. Winterhalter and U. Kleinekathöfer, Computational Modeling of Ion Transport in Bulk and through a Nanopore Using the Drude Polarizable Force Field, J. Chem. Inf. Model. 60, 3188–3203 (2020).
141] V. K. Golla, J. D. Prajapati, M. Joshi and U. Kleinekathöfer, Exploration of Free Energy Surfaces across a Membrane Channel Using Metadynamics and Umbrella Sampling, J. Chem. Theory Comput. 16, 2751–2765 (2020).
131] S. P. Bhamidimarri, M. Zahn, J. D. Prajapati, C. Schleberger, S. Söderholm, J. Hoover, J. West, U. Kleinekathöfer, D. Bumann, M. Winterhalter and B. van den Berg, A Multidisciplinary Approach toward Identification of Antibiotic Scaffolds for Acinetobacter baumannii, Structure 27, 268–280.e6 (2019).
 V. K. Golla, E. Sans-Serramitjana, K. R. Pothula, L. Benier, J. A. Bafna, M. Winterhalter and U. Kleinekathöfer, Fosfomycin Permeation through the Outer Membrane Porin OmpF, Biophys. J. 116, 258–269 (2019).
 C. J. F. Solano, K. R. Pothula, J. D. Prajapati, P. M. De Biase, S. Y. Noskov and U. Kleinekathöfer, BROMOCEA Code: An Improved Grand Canonical Monte Carlo/Brownian Dynamics Algorithm Including Explicit Atoms, J. Chem. Theory Comput. 12, 2401–2417 (2016).
 K. R. Pothula, C. J. Solano and U. Kleinekathöfer, Simulations of Outer Membrane Channels and Their Permeability, Biochimica et Biophysica Acta (BBA) – Biomembranes 1858, 1760–1771 (2016).
 B. van den Berg, P. S. Bhamidimarri, D. J. Prajapati, U. Kleinekathöfer and M. Winterhalter, Outer-membrane Translocation of Bulky Small Molecules by Passive Diffusion, Proc. Natl. Acad. Sci. USA 112, E2991–E2999 (2015).