Modelling the folding of transmembrane proteins using a novel fragmental approach: the human ghrelin

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Modelling the folding of transmembrane proteins
using a novel fragmental approach the human
ghrelin receptor and the glutamate transporter
EAAT1
Alessandro Pedretti Giulio Vistoli
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The fragmental approach1
Aminoacid sequence of the transmembrane protein
Fragmentation in structural domains
Folding prediction of each fragment
Assembling using a global template
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Global template
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The fragmental approach2
Model validation
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HGHS-R1a ligand binding sites
Glu 124
Polar
Arg 283
Apolar
Spiroindane derivative EC50 0.6 nM
TM3
TM6
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QSAR analysis
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Conclusions

• The fragmental approach allows to obtain good
  models avoiding the construction of bovine
  rhodopsin clones.
• The computational results are confirmed by the
  good correlation between the experimental data
  and the docking scores.
• The method was successfully applied to the
  non-GPCR protein EAAT1, obtaining results
  confirmed by the experimental data.