Memprot.GPCR-ModSim: modelling and simulation of membrane proteins in a nutshell

Bioinformatics, vol. 40

Abstract

SUMMARY: Memprot.GPCR-ModSim leverages our previous web-based protocol, which was limited to class-A G protein-coupled receptors, to become the first one-stop web server for the modelling and simulation of any membrane protein system. Motivated by the exponential growth of experimental structures and the breakthrough of deep-learning-based structural modelling, the server accepts as input either a membrane-protein sequence, in which case it reports the associated AlphaFold model, or a 3D (experimental, modelled) structure, including quaternary complexes with associated proteins and/or ligands of any kind. In both cases, the molecular dynamics (MD) protocol produces a membrane-embedded, solvated, and equilibrated system, ready to be used as a starting point for further MD simulations, including ligand-binding free energy calculations. AVAILABILITY AND IMPLEMENTATION: Memprot.GPCR-ModSim web server is publicly available at https://memprot.gpcr-modsim.org/. The standalone modules for 3D modelling (PyModSim) or membrane embedding and MD equilibration (PyMemDyn) are available under CC BY-NC 4.0 license terms at the GitHub repository https://github.com/GPCR-ModSim/.

Authors 6

1. Remco L. van den Broek Aachen Division of Medicinal Chemistry Leiden Academic Centre for Drug Research

   Leiden University · Uppsala University

   Affiliation as printed

   Department of Cell and Molecular Biology, Uppsala University , BMC - Box 596 , Uppsala, SE 751 24,

   Division of Medicinal Chemistry, Leiden Academic Centre for Drug Research, Leiden University , Leiden 2333 CC,

2. Xabier Bello

   Universidade de Santiago de Compostela · Servicio Gallego de Salud

   Affiliation as printed

   Institute of Forensic Sciences, Faculty of Medicine, University of Santiago de Compostela , Hospital Clínico Universitario de Santiago de Compostela (SERGAS) Santiago de Compostela, Galicia, 15706,

3. Rebecca V Küpper

   Uppsala University

   Affiliation as printed

   Department of Cell and Molecular Biology, Uppsala University , BMC - Box 596 , Uppsala, SE 751 24,

4. Gerard J. P. van Westen Aachen Division of Medicinal Chemistry Leiden Academic Centre for Drug Research

   Leiden University

   Affiliation as printed

   Division of Medicinal Chemistry, Leiden Academic Centre for Drug Research, Leiden University , Leiden 2333 CC,

5. Willem Jespers Aachen Division of Medicinal Chemistry Leiden Academic Centre for Drug Research

   Leiden University

   Affiliation as printed

   Division of Medicinal Chemistry, Leiden Academic Centre for Drug Research, Leiden University , Leiden 2333 CC,

   MOD4SIM Pharma AB , Box 2022 , Uppsala, SE 750 02,

6. Hugo Gutiérrez‐de‐Terán corresponding

   Uppsala University

   Affiliation as printed

   Department of Cell and Molecular Biology, Uppsala University , BMC - Box 596 , Uppsala, SE 751 24,

   MOD4SIM Pharma AB , Box 2022 , Uppsala, SE 750 02,