Exploring the structural assembly of rice ADP-glucose pyrophosphorylase subunits using MD simulation.

ADP-glucose pyrophosphorylase plays a pivotal role as an allosteric enzyme, essential for starch biosynthesis in plants. The higher plant AGPase comparises of a pair of large and a pair of small subunits to form a heterotetrameric complex. Growing evidence indicates that each subunit plays a distinct role in regulating the underlying mechanism of starch biosynthesis. In the rice genome, there are four large subunit genes (OsL1-L4) and three small subunit genes (OsS1, OsS2a, and OsS2b). While the structural assembly of cytosolic rice AGPase subunits (OsL2:OsS2b) has been elucidated, there is currently no such documented research available for plastidial rice AGPases (OsL1:OsS1). In this study, we employed protein modeling and MD simulation approaches to gain insights into the structural association of plastidial rice AGPase subunits. Our results demonstrate that the heterotetrameric association of OsL1:OsS1 is very similar to that of cytosolic OsL2:OsS2b and potato AGPase heterotetramer (StLS:StSS). Moreover, the yeast-two-hybrid results on OsL1:OsS1, which resemble StLS:StSS, suggest a differential protein assembly for OsL2:OsS2b. Thus, the regulatory and catalytic mechanisms for plastidial AGPases (OsL1:OsS1) could be different in rice culm and developing endosperm compared to those of OsL2:OsS2b, which are predominantly found in rice endosperm.

Combined CADD and Virtual Screening to Identify Novel Nonpeptidic Falcipain-2 Inhibitors.

BACKGROUND: Plasmodium falciparum is the most dangerous and widespread diseasecausing species of malaria. Falcipain-2 (FP2) of Plasmodium falciparum, is a potential target for antimalarial chemotherapy since it is involved in an essential cellular function such as hemoglobin degradation during the parasite's life cycle. However, despite their central role in the life cycle of the parasite, no commercial drug targeting Falcipain-2 has been developed to date. Prior efforts to develop peptide-based drugs against Plasmodium have been futile due to their susceptibility to being degraded by host enzymes. OBJECTIVE: Here, we report computer-aided drug design of new nonpeptidic inhibitors against FP2, which are likely to be safe from degradation by host enzymes. METHODS: We have virtually screened for the probable FP2 inhibitors from the PubChem database by submitting the well-equilibrated 3-D structure of FP2. Furthermore, virtual screenings and dockings were carried out using PyRx and Discovery Studio. RESULTS: We found 15 top-ranking molecules with carbaldehyde pharmacophore having a good fit with the target protein. Based on the C-Docker values, the top 4 hits (PubChem 44138738, Pub- Chem 20983198, PubChem 20983081 and PubChem 28951461) for FP2 were identified. These four hits have been observed to bound to the active cleft of the protein. Moreover, their complexes were also found to be stable from the RMSD and Radius of Gyration analysis. CONCLUSION: The selected compounds 2-(benzylamino)-8-methylquinoline-3-carbaldehyde (Pub- Chem44138738), 6-bromo-2-(3,4-dihydro-1H-isoquinolin-2-yl)quinoline-3-carbaldehyde (Pub- Chem 20983198), 2-(3,4-dihydro-1H-isoquinolin-2-yl)-6-ethylquinoline-3-carbaldehyde(PubChem 20983081)and 2-[benzyl(methyl)amino]quinoline-3-carbaldehyde (PubChem 28951461) may be the starting point for further modification as a new type of nonpeptidic drug for malaria disease.

Identification and validation of plant miRNA from NGS data-an experimental approach.

miRNAs are class of endogenously initiated noncoding RNAs, which are most critical in gene expression and regulation at posttranscriptional level. They do so either by cleavage of the target mRNA or by translational repression. miRNAs are being given enough attention in recent years because of its role in myriad developmental processes including tumorogenesis and host-pathogen interaction. Advent of Next Generation Sequencing (NGS) technology and computational approach made it possible to pinpoint the precise role of miRNA and their target. Identification of miRNAs and their target has several approaches depending on efficiency, cost and time. The present review summarizes the developments in the field of plant miRNA w.r.t. to experimental approaches that are being followed to identify and validate the miRNAs and their targets.

Bacillus megaterium adapts to acid stress condition through a network of genes: Insight from a genome-wide transcriptome analysis.

RNA-seq analysis of B. megaterium exposed to pH 7.0 and pH 4.5 showed differential expression of 207 genes related to several processes. Among the 207 genes, 11 genes displayed increased transcription exclusively in pH 4.5. Exposure to pH 4.5 induced the expression of genes related to maintenance of cell integrity, pH homeostasis, alternative energy generation and modification of metabolic processes. Metabolic processes like pentose phosphate pathway, fatty acid biosynthesis, cysteine and methionine metabolism and synthesis of arginine and proline were remodeled during acid stress. Genes associated with oxidative stress and osmotic stress were up-regulated at pH 4.5 indicating a link between acid stress and other stresses. Acid stress also induced expression of genes that encoded general stress-responsive proteins as well as several hypothetical proteins. Our study indicates that a network of genes aid B. megaterium G18 to adapt and survive in acid stress condition.