Unraveling the molecular mechanism of novel leukemia mutations on NTRK2 (A203T & R458G) and NTRK3 (E176D & L449F) genes using molecular dynamics simulations approach.

: NTRK1, NTRK2, and NTRK3 are members of the neurotrophic receptor tyrosine kinases (NTRK) family, which encode TrkA, TrkB, and TrkC receptors, respectively. Hematologic cancers are also linked to point mutations in the NTRK gene's kinase domain. Trk fusions are the most common genetic change associated with oncogenic activity in Trk-driven liquid tumors.

Mutations in Plasmodium falciparum Kelch13 (PfK13) dysregulates PI3K/AKT signalling pathway in artemisinin resistance.

Background: PfK13 protein mutations are associated with the emergence of artemisinin resistance in Plasmodium falciparum. PfK13 protein is essential for mediating ubiquitination and controlling the PI3K/AKT pathway. Mutant PfK13 variations can interfere with substrate binding, especially with PfPI3K, which raises PfPI3K levels.

Rational design of a multivalent vaccine targeting arthropod-borne viruses using reverse vaccinology strategies.

Viruses transmitted by arthropods, such as Dengue, Zika, and Chikungunya, represent substantial worldwide health threats, particularly in countries like India. The lack of approved vaccines and effective antiviral therapies calls for developing innovative strategies to tackle these arboviruses. In this study, we employed immunoinformatics methodologies, incorporating reverse vaccinology, to design a multivalent vaccine targeting the predominant arboviruses.

Co-application of citric acid and Nocardiopsis sp. strain RA07 enhances phytoremediation potentiality of Sorghum bicolor L.

This study investigated the combined effects of citric acid (CA) and Nocardiopsis sp. RA07 on the phytoremediation potential of lead (Pb)- and copper (Cu)-contaminated soils by Sorghum bicolor L. The strain RA07 was able to tolerate Pb and Cu, and exhibited plant growth-promoting features like siderophore production, indole-3-acetic acid (IAA) synthesis, 1-aminocyclopropane-1-carboxylate (ACC) deaminase activity and phosphate solubilization.

Structural immunoinformatics approach for rational design of a multi-epitope vaccine against triple negative breast cancer.

TNBC is a highly malignant breast cancer known for its aggressive behavior affecting young female adults. The standard treatment for TNBC includes surgery, chemotherapy, and radiotherapy, which often have significant side effects. Therefore, novel preventive methods are required to combat TNBC effectively.

Scenedesmus sp. strain SD07 cultivation in municipal wastewater for pollutant removal and production of lipid and exopolysaccharides.

In this study, an efficient microalgal strain SD07 was isolated from pond wastewater and identified as Scenedesmus sp. using the 18S rRNA gene sequence analysis. The strain SD07 was grown in a variety of concentrations (25-100%) of municipal wastewater.

Plant growth-promoting actinobacterial inoculant assisted phytoremediation increases cadmium uptake in Sorghum bicolor under drought and heat stresses.

In this study, two proficient Cadmium (Cd) resistant and plant growth-promoting actinobacterial strains were isolated from metal-polluted soils and identified as Streptomyces sp. strain RA04 and Nocardiopsis sp. strain RA07.

Mutations in G6PC2 gene with increased risk for development of type 2 diabetes: Understanding via computational approach.

An increase in the fast blood glucose (FBG) levels has been linked to an increased risk of developing a chronic condition, type 2 diabetes (T2D). The mutation in the G6PC2 gene was identified to have a lead role in the modulation of FBG levels. The abnormal regulation of this enzyme influences glucose-stimulated insulin secretion (GSIS), which controls the insulin levels corresponding to the system's glucose level.

Exome array identifies functional exonic biomarkers for pediatric dental caries.

Background: Pediatric dental caries is common among Arab children, however we are still searching for possible genes and molecular mechanisms that influence caries development.

Aim: To identity genetic predispositions of dental caries among Saudi children with high DMFT (Decayed, Missing, and Filled Teeth).

Design: This case-control study analysed putative functional exonic-variants (n = 243,345) to study the molecular genetics of pediatric caries with high dmft index, 8.

Investigation of nonsynonymous mutations in the spike protein of SARS-CoV-2 and its interaction with the ACE2 receptor by molecular docking and MM/GBSA approach.

COVID-19 is an infectious and pathogenic viral disease caused by SARS-CoV-2 that leads to septic shock, coagulation dysfunction, and acute respiratory distress syndrome. The spreading rate of SARS-CoV-2 is higher than MERS-CoV and SARS-CoV. The receptor-binding domain (RBD) of the Spike-protein (S-protein) interacts with the human cells through the host angiotensin-converting enzyme 2 (ACE2) receptor.

The Structural Effect of FLT3 Mutations at 835th Position and Their Interaction with Acute Myeloid Leukemia Inhibitors: In Silico Approach.

FMS-like tyrosine kinase 3 (FLT3) gene mutations have been found in more than one-third of Acute Myeloid Leukemia (AML) cases. The most common point mutation in FLT3 occurs at the 835th residue (D835A/E/F/G/H/I/N/V/Y), in the activation loop region. The D835 residue is critical in maintaining FLT3 inactive conformation; these mutations might influence the interaction with clinically approved AML inhibitors used to treat the AML.

Cultivation of Nostoc sp. LS04 in municipal wastewater for biodiesel production and their deoiled biomass cellular extracts as biostimulants for Lactuca sativa growth improvement.

In this study, seven different cyanobacteria (LS01-LS07) were isolated from paddy field water and among them, the isolate LS04 was able to grow well on municipal wastewater. The LS04 isolate was identified as Nostoc sp. (designated as Nostoc sp.

Network analysis of transcriptomics data for the prediction and prioritization of membrane-associated biomarkers for idiopathic pulmonary fibrosis (IPF) by bioinformatics approach.

Idiopathic pulmonary fibrosis (IPF) is a rare yet crucial persistent lung disorder that actuates scarring of lung tissues, which makes breathing difficult. Smoking, environmental pollution, and certain viral infections could initiate lung scarring. However, the molecular mechanism involved in IPF remains elusive.

Polyhydroxybutyrate production from ultrasound-aided alkaline pretreated finger millet straw using Bacillus megaterium strain CAM12.

In this study, finger millet straw (FMS) was utilized for the production of Polyhydroxybutyrate (PHB) by Bacillus megaterium strain CAM12. Ultrasound-assisted alkaline (NaOH) pretreatment of FMS under optimized conditions followed by enzymatic saccharification resulted in the maximum delignification (72%), hydrolysis yield (84%), glucose yield (86%) and xylose yield (61%). The effects of different pH, temperature, incubation period, inoculum concentration, agitation speed and FMS enzymatic hydrolysates concentration were investigated to improve the PHB production.

Removal of nutrients from domestic wastewater by microalgae coupled to lipid augmentation for biodiesel production and influence of deoiled algal biomass as biofertilizer for Solanum lycopersicum cultivation.

In this study, Chlorella sp., Scenedesmus sp., and their consortium were used for the biorefinery approach.

Deciphering the Role of Filamin B Calponin-Homology Domain in Causing the Larsen Syndrome, Boomerang Dysplasia, and Atelosteogenesis Type I Spectrum Disorders via a Computational Approach.

Filamins (FLN) are a family of actin-binding proteins involved in regulating the cytoskeleton and signaling phenomenon by developing a network with F-actin and FLN-binding partners. The FLN family comprises three conserved isoforms in mammals: FLNA, FLNB, and FLNC. FLNB is a multidomain monomer protein with domains containing an actin-binding N-terminal domain (ABD 1-242), encompassing two calponin-homology domains (assigned CH1 and CH2).

Effect of novel leukemia mutations (K75E & E222K) on interferon regulatory factor 1 and its interaction with DNA: insights from molecular dynamics simulations and docking studies.

Interferon regulatory factor 1 (IRF-1) plays a vital role in cell proliferation and cell differentiation by acting as a tumor suppressor gene and its role is linked to various types of cancers, including leukemia and pre-leukemia myelodysplasia. Mutations in the coding region of the IRF-1 are likely to influence the IRF-1 and its DNA binding affinity. The molecular mechanism of the DNA recognition with the IRF-1 protein upon mutations is still unknown.

State-of-the-art tools unveil potent drug targets amongst clinically approved drugs to inhibit helicase in SARS-CoV-2.

Introduction: The extreme health and economic problems in the world due to the SARS-CoV-2 infection have led to an urgent need to identify potential drug targets for treating coronavirus disease 2019 (COVID-19). The present state-of-the-art tool-based screening was targeted to identify drug targets among clinically approved drugs by uncovering SARS-CoV-2 helicase inhibitors through molecular docking analysis.

Material And Methods: Helicase is a vital viral replication enzyme, which unwinds nucleic acids and separates the double-stranded nucleic acids into single-stranded nucleic acids.

Comprehensive in silico screening and molecular dynamics studies of missense mutations in Sjogren-Larsson syndrome associated with the ALDH3A2 gene.

Sjögren-Larsson syndrome (SLS) is an autoimmune disorder inherited in an autosomal recessive pattern. To date, 80 missense mutations have been identified in association with the Aldehyde Dehydrogenase 3 Family Member A2 (ALDH3A2) gene causing SLS. Disruption of the function of ALDH3A2 leads to excessive accumulation of fat in the cells, which interferes with the normal function of protective membranes or materials that are necessary for the body to function normally.

Application of Computational Biology and Artificial Intelligence Technologies in Cancer Precision Drug Discovery.

Artificial intelligence (AI) proves to have enormous potential in many areas of healthcare including research and chemical discoveries. Using large amounts of aggregated data, the AI can discover and learn further transforming these data into "usable" knowledge. Being well aware of this, the world's leading pharmaceutical companies have already begun to use artificial intelligence to improve their research regarding new drugs.

A computational approach for investigating the mutational landscape of RAC-alpha serine/threonine-protein kinase (AKT1) and screening inhibitors against the oncogenic E17K mutation causing breast cancer.

Breast cancer (BC) is the most commonly diagnosed cancer among females worldwide, and among the BC-associated mutations in various proteins, mutations in the RAC-alpha serine/threonine-protein kinase (AKT1) remain the most dominant. We thus attempted to understand the potential molecular pathogenicity profile of the mutations in AKT1 using a comprehensive computational protocol involving analyses of biochemistry-disruption and destabilizing properties and conservation. Our predictions revealed that E17K, R67W, V164G, E319G, R391G, D32Y, L52H, L52R, and W80R were the most pathogenic mutations.

Prioritization of SNPs in y+LAT-1 culpable of Lysinuric protein intolerance and their mutational impacts using protein-protein docking and molecular dynamics simulation studies.

Lysinuric protein intolerance (LPI) is a rare, yet inimical, genetic disorder characterized by the paucity of essential dibasic amino acids in the cells. Amino acid transporter y+LAT-1 interacts with 4F2 cell-surface antigen heavy chain to transport the required dibasic amino acids. Mutation in y+LAT-1 is rumored to cause LPI.

Selective Glucocorticoid Receptor Properties of GSK866 Analogs with Cysteine Reactive Warheads.

Synthetic glucocorticoids (GC) are the mainstay therapy for treatment of acute and chronic inflammatory disorders. Due to the high adverse effects associated with long-term use, GC pharmacology has focused since the nineties on more selective GC ligand-binding strategies, classified as selective glucocorticoid receptor (GR) agonists (SEGRAs) or selective glucocorticoid receptor modulators (SEGRMs). In the current study, GSK866 analogs with electrophilic covalent-binding warheads were developed with potential SEGRA properties to improve their clinical safety profile for long-lasting topical skin disease applications.

Mutational Analysis on Membrane Associated Transporter Protein (MATP) and Their Structural Consequences in Oculocutaeous Albinism Type 4 (OCA4)-A Molecular Dynamics Approach.

Oculocutaneous albinism type IV (OCA4) is an autosomal recessive inherited disorder which is characterized by reduced biosynthesis of melanin pigmentation in skin, hair, and eyes and caused by the genetic mutations in the membrane-associated transporter protein (MATP) encoded by SLC45A2 gene. The MATP protein consists of 530 amino acids which contains 12 putative transmembrane domains and plays an important role in pigmentation and probably functions as a membrane transporter in melanosomes. We scrutinized the most OCA4 disease-associated mutation and their structural consequences on SLC45A2 gene.