Detail

Keywords

Membrane Transport Proteins; Membranes; Molecular Dynamics Simulation; Neurotransmitter Transporters; Sequence Alignment; Structural Homology, Protein

Research group(s)

• Stockner Lab
  Head: Thomas Stockner
  Research Area: Computational Pharmacology, Membrane Transporters, Ion Channels, MD simulations, AI
  Members:
  Thomas Stockner

Research interests

New Homepage: Please follow this link to reach the new homepage of the Stockner-Lab:

http://www.meduniwien.ac.at/stockner-lab

The main research topics of the Stockner Lab include membrane transporters from the primary active ABC transporter family and the secondary active neurotransmitter transporters as well as TRP ion channels. The main goal is to achieve a

comprehensive understanding of protein function. Molecular Dynamics (MD) simulations can in principle provide insights with unrivalled time and positional resolutions, but require experimental data to provide verification. Experiments using pharmacological and electrophysiological approaches are conducted within the Stockner Lab, and frequently with collaboration partners.

Key to the success of research on the complex molecular machines is interdisciplinarity through combining experiments with modelling and simulations, because no method alone can answer the complex questions that link structure with protein dynamics, function, binding an the driving forces energising structural changes and thus function. Our main areas of research include:

• Structure, function and dynamics of transporters and channels
• The transport cycle or secondary active transporters
• Gating and ion permeation of TRP ion channels
• Protein lipid interactions and functional roles of lipids
• Interactions of substrate and inhibitors with transporters
• Enthalpy, entropy and kinetics
• Energy coupling of transporters

Techniques, methods & infrastructure

We use modelling and simulation techniques as the platform for integrating experiments and theory. We implement and use different techniques of computational pharmacology, including molecular dynamics (MD) simulations, free energy and entropy calculations, but also apply structural bioinformatics methods and continue expanding the use of advanced Machine Learning approaches. Molecular Dynamics (MD) simulations can in principle provide insights with unrivalled time and positional resolutions, but require experimental data to provide verification and to set boundary conditions. These techniques are always used in close conjunction with experiments as we aim to discover new fundamental principles behind biological matter to explain essential biological phenomena from a quantitative, physicochemical and pharmacological perspective. Experiments are also conducted within the Stockner Lab, and frequently with collaboration partners.

Grants

• The role of phosphorylation in organic cation transporter 3 (2024)
  Source of Funding: FWF (Austrian Science Fund), Stand-Alone Project
  Principal Investigator
• Regulation von TRPV6 durch PIP2 Lipide des Paralipidom (2023)
  Source of Funding: FWF (Austrian Science Fund), Stand-Alone Projects
  Principal Investigator
• Analysis of missense mutations in organic cation transporter (2021)
  Source of Funding: FWF (Austrian Science Fund), Stand-Alone Projects
  Principal Investigator
• Illuminating the TRPC3 signaling machinery (2019)
  Source of Funding: FWF (Austrian Science Fund), Stand alone projects
  Principal Investigator
• NeuroTrans: Neurotransmitter Transporters: from single molecules to human pathologies (2019)
  Source of Funding: EU, Marie Sklodowska Curie Action: European Training Network
  Coordinator of the collaborative project
• Energy coupling in the serotonin transporter (2018)
  Source of Funding: FWF (Austrian Science Fund), Stand-Alone Projects
  Principal Investigator
• Transport cycle of the ABC transporter ABCB1 (2010)
  Source of Funding: FWF (Austrian Science Fund), Stand-Alone Projects
  Principal Investigator
• Transmembrane Transporters in Health and Disease (project part leader) (2007)
  Source of Funding: FWF (Austrian Science Fund), Special Research Programmes (SFB35)
  Principal Investigator
• Analysis of missense mutations in organic cation transporter (0)
  Source of Funding: FWF (Austrian Science Fund), Stand alone project
  Coordinator of the collaborative project

Selected publications

1. Gradisch, R. et al. (2024) ‘Ligand coupling mechanism of the human serotonin transporter differentiates substrates from inhibitors’, Nature Communications, 15(1). Available at: https://doi.org/10.1038/s41467-023-44637-6.
2. Alves da Silva, L. et al. (2024) ‘Free energy profile of the substrate‐induced occlusion of the human serotonin transporter’, Journal of Neurochemistry [Preprint]. Available at: https://doi.org/10.1111/jnc.16061.
3. Szöllősi, D. et al., 2018. Dissecting the Forces that Dominate Dimerization of the Nucleotide Binding Domains of ABCB1. Biophysical Journal, 114(2), pp.331–342. Available at: http://dx.doi.org/10.1016/j.bpj.2017.11.022.
4. Khanppnavar, B. et al. (2022) ‘Structural basis of organic cation transporter-3 inhibition’, Nature Communications, 13(1). Available at: https://doi.org/10.1038/s41467-022-34284-8.
5. Erkan‐Candag, H. et al. (2022) ‘Diacylglycerols interact with the L2 lipidation site in TRPC3 to induce a sensitized channel state’, EMBO reports, 23(7). Available at: https://doi.org/10.15252/embr.202154276.