Rajasekaran Ekambaram

Bio: Rajasekaran Ekambaram is an academic researcher from Hanyang University. The author has contributed to research in topics: Plasmodium falciparum & Proteome. The author has an hindex of 2, co-authored 3 publications receiving 4 citations.

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.

Abstract: 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

Abstract: 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.

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

Abstract: Summary: 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. Contact: klaus@hanyang.ac.kr Supplementary information: Supplementary data are available at Bioinformatics online.

Analeptic activity of 2-Hydroxyl-5-Nitrobenzaldehyde: Experimental, DFT studies, and in silico molecular docking approach

Abstract: This study was carried out to evaluate the spectroscopic, molecular properties, and in silico biological assessment of 2-Hydroxyl-5-Nitrobenzaldehyde (NSA) characterized by FT-IR, UV, NMR spectral, and first-principle density functional theory (DFT). The optimized molecular geometry, the vibrational wavenumbers, and infrared intensities activities were calculated by using the density functional theory (DFT) B3LYP method with a 6–311++G(d,p) basis set. The detailed interpretation of the vibrational spectra was assigned by VEDA program. The results of NBO analysis show that LP(3)O12 and LP(2)O13 bonding orbitals participated as donors and the π*N10–O11 and π*C2–C3 antibonding orbitals as acceptors in all the four phases understudy with occupancies in the range of 1.45453, 1.85287 leading to the stabilization energy of 160.60 and, 30.55 kcal/mol, which results in intramolecular charge transfer leading to the stabilization of the molecule. Moreover, Drug likeness properties of NSA are predicted. The predicted ADMET properties showed high gastrointestinal absorption, does not permeant the brain–blood barrier, nor any Cytochrome P450 inhibition (1A2, 2C19, 2C9, 2DA, 3A4, and 3A4) without violating any of the Lipinski rules. The result from the molecular docking showed that NSA has the highest negative mean binding affinity of −5.71 kcal/mol, followed by CFN and EDE which are approximately equal at −5.176 and −5.004 kcal/mol respectively and added to a more significant hydrogen bond with amino acids residues of the selected receptor proteins. Therefore, it could be said that NSA is a potential analeptic agent.

Phytochemical Profiling in Conjunction with In Vitro and In Silico Studies to Identify Human α-Amylase Inhibitors in Leucaena leucocephala (Lam.) De Wit for the Treatment of Diabetes Mellitus.

Abstract: Bioactive constituents from natural sources are of great interest as alternatives to synthetic compounds for the treatment of various diseases, including diabetes mellitus. In the present study, phytochemicals present in Leucaena leucocephala (Lam.) De Wit leaves were identified by gas chromatography-mass spectrometry and further examined by qualitative and quantitative methods. α-Amylase enzyme activity assays were performed and revealed that L. leucocephala (Lam.) De Wit leaf extract inhibited enzyme activity in a dose-dependent manner, with efficacy similar to that of the standard α-amylase inhibitor acarbose. To determine which phytochemicals were involved in α-amylase enzyme inhibition, in silico virtual screening of the absorption, distribution, metabolism, excretion, and toxicity properties was performed and pharmacophore dynamics were assessed. We identified hexadecenoic acid and oleic acid ((Z)-octadec-9-enoic acid) as α-amylase inhibitors. The binding stability of α-amylase to those two fatty acids was confirmed in silico by molecular docking and a molecular dynamics simulation performed for 100 ns. Together, our findings indicate that L. leucocephala (Lam.) De Wit-derived hexadecanoic acid and oleic acid are natural product-based antidiabetic compounds that can potentially be used to manage diabetes mellitus.

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.

Abstract: 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.