Structure prediction and binding sites analysis of curcin protein of Jatropha curcas using computational approaches

Abstract

Ribosome inactivating proteins (RIPs) are defense proteins in a number of higher-plant species that are directly targeted toward herbivores. Jatropha curcas is one of the biodiesel plants having RIPs. The Jatropha seed meal, after extraction of oil, is rich in curcin, a highly toxic RIP similar to ricin, which makes it unsuitable for animal feed. Although the toxicity of curcin is well documented in the literature, the detailed toxic properties and the 3D structure of curcin has not been determined by X-ray crystallography, NMR spectroscopy or any in silico techniques to date. In this pursuit, the structure of curcin was modeled by a composite approach of 3D structure prediction using threading and ab initio modeling. Assessment of model quality was assessed by methods which include Ramachandran plot analysis and Qmean score estimation. Further, we applied the protein-ligand docking approach to identify the r-RNA binding residue of curcin. The present work provides the first structural insight into the binding mode of r-RNA adenine to the curcin protein and forms the basis for designing future inhibitors of curcin. Cloning of a future peptide inhibitor within J. curcas can produce non-toxic varieties of J. curcas, which would make the seed-cake suitable as animal feed without curcin detoxification.

Understanding the Mechanism of Atovaquone Drug Resistance in Plasmodium falciparum Cytochrome b Mutation Y268S Using Computational Methods

“…This protocol uses ChiRotor algorithm and CHARMm force field to systematically search for optimal side-chain conformation of all residues and generates a model structure with the best side-chain conformation. Model quality estimation is critically important in computational protein modeling, since the accuracy of a model determines its suitability for specific biological and biochemical experimental design [45] . The fitness of a protein sequence in its current 3D environment before and after side chain refinement was evaluated by Verify Protein (Profiles-3D).…”

Structural modeling and in silico analysis of non-synonymous single nucleotide polymorphisms of human 3β-hydroxysteroid dehydrogenase type 2

“…They are (a) torsion energy potential based on three consecutive amino acids used to measure local geometry, (b) two distance dependent potentials to assess long range interactions based on Cβ atoms and all atoms, (c) solvent potential (d) solvent accessibility. The QMEAN Z-score provides an estimate of the absolute quality of a model by comparing it to same sized reference structures present in the PDB and solved by experimental techniques ( Srivastava et al, 2012 ). QMEAN Z-score was used to estimate the ‘degree of nativeness’ of the predicted structure.…”

Identification, characterization and structure analysis of a type I ribosome-inactivating protein from Sapium sebiferum (Euphorbiaceae)

“…Among the eight residues, six were exactly same as those in the active site of ricin (Asn122, Ala79, Tyr80, Ser176, Ile172, Arg180) [45]. It has been previously suggested that ricin has a very high specificity to adenine as it depurinates adenosine from roughly 7000 nucleotides in eukaryotic ribosomes [46].…”