title: Structure of the 40S ribosomal subunit ofPlasmodium falciparumby homology andde novomodeling.
abstract: Generation of three dimensional structures of macromolecules usingin silicostructural modeling technologies such as homology andde novomodeling has improved dramatically and increased the speed by which tertiary structures of organisms 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, a process that has the potential to increase the speed of scientific discovery. In this study, homology modeling and structure prediction tools such as RNA123 and SWISS-MODEL were used to generate the 40S ribosomal subunit fromPlasmodium falciparum.This structure was modeled using the published crystal structure fromTetrahymena thermophila, a homologous eukaryote. In the absence of thePlasmodium falciparum40S ribosomal crystal structure, the model accurately depicts a global topology, secondary and tertiary connections, and gives an overall root mean square deviation (RMSD) value of 3.9 Å relative to the template׳s crystal structure. Deviations are somewhat larger in areas with no homology between the templates. These results demonstrate that this approach has the power to identify motifs of interest in RNA and identify potential drug targets for macromolecules whose crystal structures are unknown. The results also show the utility of RNA homology modeling software for structure determination and lay the groundwork for applying this approach to larger and more complex eukaryotic ribosomes and other RNA-protein complexes. Structures generated from this study can be used inin silicoscreening experiments and lead to the determination of structures for targets/hit complexes.
authors.affiliation: Center for Biotechnology and Bioinformatics, Chiromo Campus, University of Nairobi. HEP Bioinformatics Consultants Ltd., Nairobi, Kenya.
authors.forename: Harrison Ndung'u
authors.initials: HN
authors.lastname: Mwangi
authors.affiliation: Department of Computing Informatics, University of Nairobi, Nairobi, Kenya.
authors.forename: Peter
authors.initials: P
authors.lastname: Wagacha
authors.affiliation: Department of Computing Informatics, University of Nairobi, Nairobi, Kenya.
authors.forename: Peterson
authors.initials: P
authors.lastname: Mathenge
authors.affiliation: DNA Software, Inc., MI 48104, USA.
authors.forename: Fredrick
authors.initials: F
authors.lastname: Sijenyi
authors.affiliation: Department of Biochemistry, Riverside Drive, Chiromo Campus, University of Nairobi, Nairobi, Kenya.
authors.forename: Francis
authors.initials: F
authors.lastname: Mulaa
keywords: 3D modeling; 40S subunit; De novo; Homology; Plasmodium falciparum; RNA structure; Ribosome