Welcome to the Linusson Lab

Our research is directed towards fundamental aspects of interactions of small-molecular ligands with proteins, using both experimental and computational techniques. The research is performed within pharmaceutical relevant projects to contribute to the discovery of new molecules against for example rheumatoid arthritis, malaria and dengue fever.

The association between molecules (ligands) and macromolecules plays a key role in biological processes. The research aims to understand how the geometry and energy of protein-ligand interactions influence the molecular recognition. The research combines computational chemistry with organic synthesis, kinetic and thermodynamic studies, structure determination and biological evaluation. The research in the group is focused on two proteins, class II major histocompatibility complex (MHCII) and acetylcholinesterase (AChE). MHCII presents peptide antigens to T-cells in the immune system and AChE terminates synaptic transmission through hydrolysis of acetylcholine.

Specific research aims in the lab include:

  • Exploration of the geometry and binding energy of non-covalent interactions in AChE-ligand complexes by organic synthesis, X-ray crystallography, kinetic and thermodynamic studies to gain knowledge of molecular recognition
  • In depth computational studies of aromatic and weak hydrogen bond interactions in AChE-ligand complexes by molecular mechanics and quantum chemistry to develop methods by which we can quantify binding energy components and estimate free energy of binding
  • Design and synthesise novel AChE ligands of medical interest by using the developed computational and experimental methods and the gained understanding of the system
  • Investigation of how the geometry and motion of MHCII/glycopeptides/T-cell complexes influence the binding energy of the non-covalent interactions, to understand and predict experimentally determined biological responses
  • Design and synthesise glycopeptides that bind stronger to the MHCII protein Aq and/or are proteolytically stable aimed to be used in vaccination studies in a mouse model for rheumatoid arthritis (RA)
  • Exploration of the molecular recognition between glycopeptides and the human MHCII protein DR4 by computer-based design, organic synthesis, X-ray crystallography and biological evaluation with the long term goal of developing a vaccine against RA
  • Design and develop synthetic insecticides to prevent infectious diseases spread by mosquitos, focusing on dengue, yellow fever and malaria

Lab members

David Andersson, Staff scientist, david.andersson AT umu.se
Rashmi Kumari, Postdoc, rashmi.kumari AT umu.se
Cecilia Engdahl, Researcher, cecilia.engdahl AT umu.se
Cecilia Lindgren, Researcher, cecilia.lindgren AT umu.se
Sofie Knutsson, Researcher, sofie.knutsson AT umu.se
Tomas Kindahl, Researcher, tomas.kindahl AT umu.se

Former lab members                                                             

  • Brijesh Kumar Mishra, currently Assistant Professor at International Institute of Information Technology, Bangalore, India
  • Urszula Uciechowska, currently at the Medical University in Gdansk, Poland
  • Ida Andersson, currently at Karolinska Institute, Stockholm, Sweden
  • Anton Lindström, currently at University Hospital of Umeå, Sweden
  • Lotta Berg, currently at Umeå Biotech Incubator, Umeå, Sweden

Contact information

Anna Linusson, Professor
Department of Chemistry
Umeå University
SE-901 87 Umeå, Sweden
anna.linusson@chem.umu.se
office phone: +46-90-786 68 90

Publications

Author

Title

Year sorteringsordning

Fulltext

Allgardsson, Anders
Andersson, C. David
Akfur, Christine; et al.

An unusual dimeric inhibitor of acetylcholinesterase: cooperative binding of crystal violet
Molecules, 22(9)

2017

-

Knutsson, Sofie
Kindahl, Tomas
Engdahl, Cecilia; et al.

N-Aryl-N'-ethyleneaminothioureas effectively inhibit acetylcholinesterase 1 from disease-transmitting mosquitoes
European Journal of Medicinal Chemistry, 134: 415-427

2017

-

Allgardsson, Anders
Berg, Lotta
Akfur, Christine; et al.

Structure of a prereaction complex between the nerve agent sarin, its biological target acetylcholinesterase, and the antidote HI-6
Proceedings of the National Academy of Sciences of the United States of America, 113(20): 5514-5519

2016

-

Berg, Lotta
Mishra, Brijesh Kumar
Andersson, C. David; et al.

The Nature of Activated Non-classical Hydrogen Bonds: A Case Study on Acetylcholinesterase-Ligand Complexes
Chemistry - A European Journal, 22(8): 2672-2681

2016

-

Engdahl, Cecilia
Knutsson, Sofie
Ekström, Fredrik; et al.

Discovery of selective inhibitors targeting acetylcholinesterase 1 from disease-transmitting mosquitoes
Journal of Medicinal Chemistry, 59(20): 9409-9421

2016

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Engdahl, Cecilia
Knutsson, Sofie
Fredriksson, Sten-Åke; et al.

Acetylcholinesterases from the Disease Vectors Aedes aegypti and Anopheles gambiae: Functional Characterization and Comparisons with Vertebrate Orthologues
PLoS ONE, 10(10)

2015

Download

Karlberg, Tobias
Klepsch, Mirjam
Thorsell, Ann-Gerd; et al.

Structural Basis for Lack of ADP-ribosyltransferase Activity in Poly(ADP-ribose) Polymerase-13/Zinc Finger Antiviral Protein
Journal of Biological Chemistry, 290(12): 7336-7344

2015

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Lindgren, Cecilia
Andersson, Ida E.
Berg, Lotta; et al.

Hydroxyethylene isosteres introduced in type II collagen fragments substantially alter the structure and dynamics of class II MHC A(q)/glycopeptide complexes
Organic and biomolecular chemistry, 13(22): 6203-6216

2015

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Ekblad, Torun
Lindgren, Anders E. G.
Andersson, C. David; et al.

Towards small molecule inhibitors of mono-ADP-ribosyltransferases
European Journal of Medicinal Chemistry, 95: 546-551

2015

Download

Andersson, C. David
Hillgren, J. Mikael
Lindgren, Cecilia; et al.

Benefits of statistical molecular design, covariance analysis, and reference models in QSAR: a case study on acetylcholinesterase
Journal of Computer-Aided Molecular Design, 29(3): 199-215

2015

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