“Adventures in Protein Biophysics (Plexins, Eph receptor and Ras GTPases) with experimental methods, molecular dynamics simulations and AlphaFold predictions.”
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Date and Time
Friday, September 18, 2026, 2:30 PM – 3:30 PM
Location
Hybrid (Cryo-EM Building and Zoom)
Speaker
Professor Matthias Buck
Department of Physiology and Biophysics, Case Western Reserve University, School of Medicine, Cleveland, Ohio, United States of America (Currently: LT JSPS Fellow in Hiroaki Suga Lab., Department of Chemistry, University of Tokyo)
Abstract
In this presentation I will provide an overview of work in my lab. ranging from all atom and coarse grained molecular dynamics simulations on type 1 transmembrane proteins (TM) and membrane attached Ras [1] and our use of AlphaFold2Multimer/AF3 [2]. Synergy (but also difficulties in matching some computational studies with experiments) are outlined for work on protein-protein and protein-membrane interactions. Our work has allowed us to advance several concepts in protein biophysics, such as conformational and dynamic allostery [3], protein entropy changes which enable subsequent binding events [4], the role of different membrane lipids on transmembrane segment protein configurations [5] and that several protein complexes in cell signaling are dynamic entities [1,6]. In the Suga lab., I am working on the next generation design and selection of transmembrane peptides [7] which regulate plexin and Eph receptors.
[1] Li ZL, Prakash P, Buck M. (2018) A “Tug of War” Maintains a Dynamic Protein-Membrane Complex: Molecular Dynamics Simulations of C-Raf RBD-CRD Bound to K-Ras4B at an Anionic Membrane. ACS Cent Sci. 4:298-305.
[2] Sahoo, A.R., Souza, PCT., Meng,, Y., & Buck, M. (2023) “Transmembrane region dimer structures of Type 1 receptors readily sample alternate configurations: MD simulations using the Martini 3 coarse grained model compared to AlphaFold2 Multimer” Structure 31:735-745.e2
[3] Li ZL, Müller-Greven J, Kim S, Tamagnone L, Buck M. (2021) Plexin-Bs enhance their GAP activity with a novel activation switch loop generating a cooperative enzyme. Cell Mol Life Sci. 78:1101-1112.
[4] Li ZL, Mattos C, Buck M. (2022) Computational studies of the principle of dynamic-change-driven protein interactions. Structure 30:909-916.e2.
[5] Sahoo, AR., Bhattarai, N., Buck, M. (2025) Cholesterol-Dependent Dimerization and Conformational Dynamics of EphA2 Receptors: Insights from Coarse-Grained and All-Atom Simulations Structure 33: 1275-1287.
[6] Zhang L, Buck M. (2017) Molecular Dynamics Simulations Reveal Isoform Specific Contact Dynamics between the Plexin Rho GTPase Binding Domain (RBD) and Small Rho GTPases Rac1 and Rnd1. J Phys Chem B. 121:1485-1498.
[7] Westerfield JM, Sahoo AR, Alves DS, Grau B, Cameron A, Maxwell M, Schuster JA, Souza PCT, Mingarro I, Buck M. & Barrera FN. (2021) “Conformational Clamping by a Membrane Ligand Activates the EphA2 Receptor.” J Mol Biol. 433:167144
Profile
Dr Matthias Buck is a distinguished academic and researcher serving as a Professor at Case Western Reserve University (CWRU) in Cleveland, Ohio. He holds primary appointments in the Department of Physiology and Biophysics, with additional roles as an Associate Professor in Pharmacology and an Assistant Professor in Neurosciences. Furthermore, he is a prominent member of the Molecular Oncology Program at the Case Comprehensive Cancer Center.
