Introduction: Sickle cell disease is characterized by a point mutation involving substitution
of glutamic acid at position 6 to valine. Encoded in this hydrophobic mutation is both an intrinsic capacity
for the beta globin molecules to assemble into thermodynamically favoured polymeric states as
well as a rational way of interrupting the aggregation.
Methods: In this work, starting with a theoretical model that employs occlusive binding onto the beta
globin aggregation surface and using a range of computational methods and an effective energy for
screening, a number of FDA approved drugs with computed aggregation inhibitory activities were
Results and Conclusion: The validity of the model was confirmed using sickling tests, after which
pharmacophore models as well the structural basis for the observed antisickling effects were identified.