Biophysical Society Thematic Meeting | Bucharest 2026

Biophysics of Membrane Reactions in Brian

Thursday Speaker Abstracts

MOLECULAR MODELING OF THE STRUCTURE AND FUNCTION OF THE GLUTAMATE RECEPTORS Maria G Kurnikova Carnegie Mellon University, Chemistry, Pittsburgh, PA, USA Ionotropic glutamate receptors (iGluR) are responsible for the initiation of excitatory transmission in the central nervous system (CNS). They play important roles in synaptic plasticity and long-term potentiation, while their dysfunction causes a variety of diseases, including neurodegenerative diseases and epilepsy. IGLURs are, thus, potential targets of pharmacological agents. In order to understand structure – function relationships in these proteins, we employ methods of molecular modeling, computational drug design, and machine learning (ML). Computational modeling is important for bridging the gap between low resolution functional experiments and static structures from X-ray and cryo-EM. Glutamate receptors exhibit a distinctly modular multi-domain structure. Modeling individual modules (substructures) of iGluRs has been instrumental in gaining insights into molecular determinants of functional properties. Recent successes in algorithm development and new computational platforms allow us to model real-time dynamics of conversion between different functional states of the receptor, understand allosteric relationships between ligand binding and channel opening as well as to predict how blockers and non-competitive inhibitors bind and prevent channel functioning. Drug design specific to ionotropic glutamate receptors is also becoming an important sub-field of theoretical modeling in iGluRs. 1. Yelshanskaya MV, Patel DS, Kottke CM, Kurnikova MG, Sobolevsky AI, Opening of glutamate receptor channel to subconductance levels. Nature 605(7908):172 (2022) 2. Gangwar SP, Yelshanskaya MV, Nadezhdin KD,Yen LY, Newton Th.P, Aktolun M, Kurnikova MG, Sobolevsky AI, Kainate receptor channel opening and gating mechanism. Nature 630(8017):762 (2024) 3. Gangwar SP, Yelshanskaya MV, Aktolun M, Yen LY, Newton Th.P, Stromgaard K, Kurnikova MG, Sobolevsky AI, Trapping of spermine, Kukoamine A, and polyamine toxin blockers in GluK2 kainate receptor channels, Nat. Com., 15: 10257, (2024) 4. Gutkin E, Narangoda C, Kurnikova MG, Computing Ligand Binding Free Energy in a Large Flexible Pocket of a Large Protein. ChemRxiv, DOI: 10.26434/chemrxiv-2024-87xr8 (2024)

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