[Seminar] Adventures in Protein Biophysics (Plexins, Eph receptor and Ras GTPases) over two decades: experimental methods, molecular dynamics simulations and AlphaFold predictions by Prof. Matthias Buck, Case Western Reserve University, USA

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:
Prof. Matthias Buck, Department of Physiology and Biophysics, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA

Currently: LT JSPS Fellow in Hiroaki Suga Lab., Department of Chemistry, University of Tokyo

The Department of Physiology and Biophysics - School of Medicine - Case Western Reserve University
‪Matthias Buck‬ - ‪Google Scholar‬