Investigating the Characteristics and Evolution of Apical Membrane Antigen 1 (AMA1) of Plasmodium sp. using Phylogenetic Approach in Searching for Drug Candidate

Abstract

Malaria is an endemic disease caused by Plasmodium parasite with female Anopheles mosquitoes as a vector. With the increase of drug resistance Plasmodium emerging around the world, a new method should be devised against the spread of Plasmodium sp lineage. Protein evolution of  Plasmodium sp. can be an invaluable aid as an  input for rational drug design and immune-informatics methods based on the novel virulent gene that exists in these protozoa. Previously, we did data mining in the PlasmoDB database and found several proteins shared by Plasmodium, one of  them was the Apical Membrane Antigen 1 (AMA1). This protein was further analyzed for its characteristics and evolutionary properties. AMA1 protein sequences from human-infecting Plasmodium (P. falciparum, vivax, knowlesi, ovale, and malariae) and non-infectious (P. berghei, coatneyi, and cynomolgi) were retrieved from PlasmoDB. Maximum likelihood phylogenetic tree with molecular clock analysis was reconstructed from AMA1 sequences using MEGAX. Protein domain analysis was done using the INTERPRO server. Several domains that can induce protective immunity and vaccine target were found in AMA1 of those plasmodium, such as coiled-coil, disordered region, and signal peptide domain. Furthermore, molecular clock analysis showed a similar evolutionary rate between AMA1 protein in human-infecting and non-infectious Plasmodium. Interestingly, the phylogenetic tree showed a mixed cluster of human- infecting with non-infectious, indicating a unique evolutionary relationship between Plasmodium lineage. Thus, this information could be beneficial in developing the drug and vaccine for Plasmodium-related infection.


Keywords: AMA1, drug target, protein domain, protein evolution, Plasmodium.

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