Modelling metal-protein interactions

NAISS 2023/5-306


NAISS Medium Compute

Principal Investigator:

Astrid Gräslund


Stockholms universitet

Start Date:


End Date:


Primary Classification:

10603: Biophysics

Secondary Classification:

10602: Biochemistry and Molecular Biology



Modelling metal-protein interactions In our experiments we will conduct molecular dynamics (MD) simulations to model interactions between metal ions and disease-related proteins. Specifically, we will model different isoforms of the ApoE protein, i.e. ApoE2, ApoE3, ApoE4. We will model those different isoforms of ApoE in different protonation states, which corresponds to ApoE behavior under different pH values. We will also perform simulations of different isoforms of ApoE, under different pH and complexed with metal ions. We have previous experience in planning, performing and analyzing results of molecular dynamics simulations of peptides/proteins complexed with metal ions (Gielnik et al. Biochemistry (1)). We run the simulations on GROMACS (2) (preferable 2023 version) using the OPLS-AA (3) and GROMOS 53a6 (4) forcefields. We have performed initial simulations on the Croatian Supercomputer Bura. During these simulation, we solvated an ApoE4 tetramer protein (simulation box with 500 000 atoms) simulated for 100 ns (50 000 000 steps, 2 fs time step) with three Cu(II) ions, we got the performance of 62 ns/day (24 nodes with 480 cores). Therefore for a single simulation we need ~20 000 core hours. We plan to run and analyze a number of simulations what is equal to 100 x 1000 core hours per month over the next 12 months. Each simulation requires ~100 Gb of hard disk space (in ~20 files). The Generated trajectories will be analyzed in VMD and in bio3D R package. At the end of the project the data will be stored on external hard drives. (1) Gielnik, M.; Szymańska, A.; Dong, X.; Jarvet, J.; Svedružić, Ž. M.; Gräslund, A.; Kozak, M.; Wärmländer, S. K. T. S. Prion Protein Octarepeat Domain Forms Transient β-Sheet Structures upon Residue-Specific Binding to Cu(II) and Zn(II) Ions. Biochemistry 2023, 62 (11), 1689–1705. (2) Abraham, M. J.; Murtola, T.; Schulz, R.; Páll, S.; Smith, J. C.; Hess, B.; Lindahl, E. GROMACS: High Performance Molecular Simulations through Multi-Level Parallelism from Laptops to Supercomputers. SoftwareX 2015, 1–2, 19–25. (3) Jorgensen, W. L.; Maxwell, D. S.; Tirado-Rives, J. Development and Testing of the OPLS All-Atom Force Field on Conformational Energetics and Properties of Organic Liquids. J. Am. Chem. Soc. 1996, 118 (45), 11225–11236. (4) Oostenbrink, C.; Villa, A.; Mark, A. E.; Van Gunsteren, W. F. A Biomolecular Force Field Based on the Free Enthalpy of Hydration and Solvation: The GROMOS Force-Field Parameter Sets 53A5 and 53A6. J. Comput. Chem. 2004, 25 (13), 1656–1676.