Carbon (C), hydrogen (H), nitrogen (N), oxygen (O), and sulfur (S) atoms intrigue as they are the foundation for amino acid (AA) composition and the folding and functions of proteins and thus define and control the survival of a cell, the smallest unit of life. Here, we calculated the proteomic atom distribution in > 1500 randomly selected species across the entire current phylogenetic tree and identified uracil-5-methyltransferase (U5MTase) of the protozoan parasite Plasmodium falciparum (Pf, strain Pf3D7), with a distinct atom and AA distribution pattern. We determined its apicoplast location and in silico 3D protein structure to refocus attention exclusively on U5MTase with tremendous potential for therapeutic intervention in malaria. Around 300 million clinical cases of malaria occur each year in tropical and subtropical regions of the world, resulting in over one million deaths annually, placing malaria among the most serious infectious diseases. Genomic and proteomic research of the clades of parasites containing Pf is progressing slowly and the functions of most of the~5300 genes are still unknown. We applied a 'bottom-up' comparative proteomic atomics analysis across the phylogenetic tree to visualize a protein molecule on its actual basis -i. e., its atomic level. We identified a protruding Pf3D7-specific U5MTase, determined its 3D protein structure, and identified potential inhibitory drug molecules through in silico drug screening that might serve as possible remedies for the treatment of malaria. Besides, this atomic-based proteome map provides a unique approach for the identification of parasite-specific proteins that could be considered as novel therapeutic targets.

The cover picture shows how proteome‐based atom (C, H, N, O, S) distributions across all species of the phylogenetic tree revealed U5MTase of Plasmodium falciparum as a distinguished possible therapeutic target which in turn was used for in silico structure‐based drug design strategies (i.e., 3D protein structure modeling, virtual chemical library screening, and molecular docking) to identify imanixil as potential inhibitory drug molecule that might serve as possible remedy for the treatment of malaria. More Details can be found in the Full Paper by Subrata Pramanik, Manisha Thaker, Ananda Gopu Perumal, Rajasekaran Ekambaram, Naresh Poondla, Markus Schmidt, Pok‐Son Kim, Arne Kutzner, and Klaus Heese, please see DOI: 10.1002/minf.201900135