Thymine distribution in genes provides novel insight into the functional significance of the proteome of the malaria parasite Plasmodium falciparum 3D7.

Plasmodium falciparum (Pf)-mediated malaria is one of the most devastating diseases in the world, and the search for suitable antimalarial drugs remains an extraordinary challenge for scientists working in this area. Novel unconventional approaches could reveal new potential targets that may be useful for the treatment of malaria. We used a bioinformatics approach to analyze the entire genome of the Pf3D7 strain. Because the carbon (C-) content is a pivotal parameter that determines the hydrophobicity of a protein, which in turn controls protein folding and function, we analyzed the entire Pf3D7 proteome based on the gene's thymine (T)-controlled amino acid expression. Our data disclose a total of 14 proteins encoded by chromosome-4 and chromosome-9 that have an outstanding T-encoded and C-controlled hydrophobic character. The identification of these proteins could open new pivotal drug-targeting avenues.

Identification of a Chemotherapeutic Lead Molecule for the Potential Disruption of the FAM72A-UNG2 Interaction to Interfere with Genome Stability, Centromere Formation, and Genome Editing.

Family with sequence similarity 72 A (FAM72A) is a pivotal mitosis-promoting factor that is highly expressed in various types of cancer. FAM72A interacts with the uracil-DNA glycosylase UNG2 to prevent mutagenesis by eliminating uracil from DNA molecules through cleaving the N-glycosylic bond and initiating the base excision repair pathway, thus maintaining genome integrity. In the present study, we determined a specific FAM72A-UNG2 heterodimer protein interaction using molecular docking and dynamics. In addition, through in silico screening, we identified withaferin B as a molecule that can specifically prevent the FAM72A-UNG2 interaction by blocking its cell signaling pathways. Our results provide an excellent basis for possible therapeutic approaches in the clinical treatment of cancer.

Proteomic Atomics Reveals a Distinctive Uracil-5-Methyltransferase.

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.

CARd-3D: Carbon Distribution in 3D Structure Program for Globular Proteins.

Spatial arrangement of carbon in protein structure is analyzed here. Particularly, the carbon fractions around individual atoms are compared. It is hoped that it follows the principle of 31.45% carbon around individual atoms. The results reveal that globular protein's atoms follow this principle. A comparative study on monomer versus dimer reveal that carbon is better distributed in dimeric form than in its monomeric form. Similar study on solid versus liquid structures reveals that the liquid (NMR) structure has better carbon distribution over the corresponding solid (X-Ray) structure. The carbon fraction distributions in fiber and toxin protein are compared. Fiber proteins follow the principle of carbon fraction distribution. At the same time it has another broad spectrum of carbon distribution than in globular proteins. The toxin protein follows an abnormal carbon fraction distribution. The carbon fraction distribution plays an important role in deciding the structure and shape of proteins. It is hoped to help in understanding the protein folding and function.