Structure of the 40S ribosomal subunit from Plasmodium falciparum By Homology and De novo modeling
Abstract
Generation of the three dimensional structures of macromolecules using in silico structural
modeling technologies such as homology and de novo modeling has improved dramatically and
increased the speed in which tertiary structures of organisms of interest can be generated. This is
especially the case if a homologous crystal structure is already available. High resolution
structures can be rapidly created using only their sequence information as input and thus
increasing the speed of scientific discoveries. In this study, a host of homology modeling and
structure prediction tools such as RNA123 and SWISS -MODEL among others, were used to
generate the 40S subunit from Plasmodium jalciparum. This structure was modeled using the
published crystal structure from Tetrahymena Thermophila, a homologous eukaryote X-ray
structure. In the absence of any information from the solved Plasmodium jalciparum 40S
ribosomal crystal structure, the model accurately depicts a global topology, secondary and
tertiary connections, and gives an overall RMSD value of 3.9 A relative to the templates crystal
structure. The model accuracy is even better than prior hypothesis, though deviations are
modestly larger for areas that had no homology between the templates. These results lay ground
work for using this approach for larger and more complex eukaryotic ribosomes, as well for still
larger RNAs, RNA-protein complexes and entire ribosomal subunits. The model created will
provide a scaffold onto which in silico ligands screening can be performed with the ultimate goal
of developing new classes of anti-malarial compounds.
Citation
Harrison Ndung'u Mwangi (2013). Structure of the 40S ribosomal subunit from Plasmodiumfalciparum By Homology and De novo modeling. Master of Science in BioinformaticsPublisher
University of Nairobi