A Bioinformatics Analysis and Homology 3D Modeling of Dihydroxy-orotate-dehydrogenase of Plasmodium ovale
The infection of Plasmodium vivax is relatively less virulent than the deathliest Plasmodium falciparum. However, it still can lead to a fatal case and often induces recurring malaria due to dormant parasites in the liver. Thus, the research to study the drug to treat Plasmodium vivax is essential, where the enzyme dihydroorotate dehydrogenase (DHODH) has recently become a new drug target. However, the drug-enzyme interaction study has only recently been conducted in Plasmodium falciparum (pfDHODH) due to the lack of the 3D structure of enzyme DHODH from Plasmodium vivax that is crucial for the study. Therefore, this study aimed to perform the modelling study of Plasmodium vivax DHODH (PvDHODH) to create a 3D structure as a basis for drug-protein interaction study in upcoming studies. Sequence pvDHODH (Accession: SCO68359.1) was used in homology modelling using Modeller 10.2 with the crystal structure of DHODH from DHODH (Accession: 7KZY) as a template. Overall, the model generated from the homology modelling was considered a good model, and the 3D structure was close to the native state according to several parameters, including DOPE score, GA341 score, QMEAN4 value, 3D-1D score, ERRAT2 score, and ProSA score. Ramachandran plot also revealed that almost all amino acids were distributed in the desirable and allowed area (99.1%), and only 0.9% were in generously allowed regions. Superimposition of the model with the template also indicated that the model has an almost similar structure and amino acids positioning, including in the binding pocket and active site. Therefore, the model can be used for downstream analysis in drug-protein interaction studies. Nevertheless, some improvements can still be performed to upgrade the quality of the model by deleting unaligned residues on the C-terminal and realigning the residues at the doubting site.
Authors:
Rudi Nirwantono, Khoirunnisa Assidqi, Alam Ahmad Hidayat, Joko Pebrianto Trinugroho, and Bens Pardamean
2023 International Conference on Informatics, Multimedia, Cyber and Information Systems, ICIMCIS 2023