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UNIVERSITY OF BUCHAREST
FACULTY OF PHYSICS Guest
2024-11-23 17:45 |
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Conference: Bucharest University Faculty of Physics 2023 Meeting
Section: Biophysics; Medical Physics
Title:
RATIONAL DRUG DESIGN FOR TARGETED DRUG DELIVERY:
(bio)PHYSICS MEETS SUPER-COMPUTING AND GRAPH THEORY
Authors:
Ana-Nicoleta Bondar(1,2)
Affiliation:
1) University of Bucharest, Faculty of Physics, Atomiștilor 405, Măgurele 077125, Romania;
2) Forschungszentrum Jülich, Institute of Computational Biomedicine, IAS-5/INM-9, Wilhelm-Johnen Straße, 5428 Jülich, Germany
E-mail
nbondar@fizica.unibuc.ro
Keywords:
Abstract:
Cancer and inflammation may be characterized by acidic external pH, which impacts membrane reactions and provides therapeutic opportunities. To sense pH, cells may rely on biomolecules named proteins which utilize specific moieties whose protonation state changes in the relevant pH range. Changes in the protonation state and proton-transfer reactions involve electronic structure changes whereby covalent bonds to hydrogen atoms break or form. We use a broad range of computational (bio)physics techniques to study proteins involved in pH sensing, and peptides of direct interest to deliver cargo to cells and cell organelles with acidic pH. Given the fundamental role of fluctuating hydrogen-bond networks for proton reactions, we perform large-scale atomistic simulations of membrane protein systems, develop graph-based algorithms for efficient analyses of data sets arising from the simulations, and derive accurate force-field parameters for non-standard chemical compounds of interest. The talk will present our graph-based algorithms and applications on pH-dependent membrane pore formation and protonation-coupled membrane proteins.
References:
Bertalan E, Lesnik S, Bren U, Bondar A-N. Protein-water hydrogen-bond networks of G Protein-Coupled Receptors: Graph-based analyses of static structures and molecular dynamics. Journal of Structural Biology 212, 107634 (2020)
Bertalan E, Lesca E, Schertler GFX, Bondar A-N. C-Graphs tool with graphical user interface to dissect conserved hydrogen-bond networks: applications to visual rhodopsins. Journal of Chemical Information and Modeling, 61, 5692-5707, doi: 10.1021/acs.jcim.1c00827 (2021)
Lazaratos M, Siemers M, Brown L.S., Bondar A-N. Conserved hydrogen-bond motifs of membrane transporters and receptors. BBA – Biomembranes 1864 (2022) 183896
Siemers M, Lazaratos M, Karathanou K, Brown LS, Bondar A-N. Bridge: A graph-based algorithm to analyze dynamic H-bond networks in membrane proteins. Journal of Chemical Theory and Computation 15, 6781-6798, doi 10.1021/acs.jctc.9b00697 (2019)
Siemers M, Bondar A-N. Interactive interface for graph-based analyses of dynamic H-bond networks: Application to spike protein S. Journal of Chemical Information and Modeling 61, 2998-3014 (2021)
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