Prof. Alan Mark has made many contributions to the molecular dynamics simulation field and is associated with GROMOS/Gromacs developments. He is currently professor in the the School of Chemistry and Molecular Biosiences of the University of Queensland, St Lucia, Queensland, Australia.
Those interested in talking to Alan during his visit should contact Alexandre Bonvin (a.m.j.j.bonvin_at_uu.nl).
While in Utrecht Alan will give a Bijvoet Seminar on Tuesday March 31st at 11:00 (NPC Room O622, Kruyt building) with as title:
###Activation of cytokine receptors and transport proteins: Turning on micromachines###
Atomistic molecular dynamics simulations have been used to investigate the conformational changes within the extracellular domain (ECD) of the growth hormone receptor (GHR) [1,2], the prolactin receptor (PRLR), erythropoietin receptor (EPOR) and the epidermal growth factor receptor (EGFR) associated with the binding or removal of ligand shedding new light on the mechanism of activation of these receptors at an atomic level. In all cases, the removal of the cytokine from the ligand-bound homodimeric receptor complexes results in a rotation of the two subunits relative to each other of between 30° and 45°. The magnitude and direction of the motion observed in the simulations of GHR and EPOR are in close agreement with experiment. The similarity of the motions in all these cases and in multiple simulations suggests that the relative rotation of the ECDs could represent a general mechanism of activation of cytokine receptors.
Poger, D. and Mark, A. E. (2010) Turning the growth hormone receptor on: Direct evidence that hormone binding induces subunit rotation. Proteins: Structure, Function, and Bioinformatics. 78, 1163-1174.
Brooks, A. J., Dai, W., O’Mara, M. L., Abankwa, D., Chhabra, Y., Pelekanos, R. A., Gardon, O., Tunny, K. A., Blucher, K. M., Morton, C. J., Parker, M. W., Sierecki, E., Gambin, Y., Gomez, G. A., Alexandrov, K., Wilson, I. A., Doxastakis, M., Mark, A.E. and Waters, M. J. (2014) A new cytokine receptor activation paradigm: activation of JAK2 by the Growth Hormone Receptor. Science, 344, 1249783.
Groothuizen, F., Poger, D. and Mark, A. E. (2010) Activating the prolactin receptor: Effect of the ligand on the conformation of the extracellular domain. J.Chem. Theory Comput. 6, 3274-3283
Poger, D. and Mark, A. E. (2014) The Activation of the Epidermal Growth Factor Receptor: a Series of Twists and Turns. Biochemistry, 53, 2710–2721.