The SARS-CoV-2 is the causative agent of COVID-19 pandemic that causing a global health emergency. lack targeted therapeutics and limited treatment options have triggered scientific community to develop new vaccines or small molecule against various targets SARS-CoV-2. main protease (Mpro) well characterized attractive drug target because its crucial role in processing polyproteins which are required for viral replication. In order provide potential lead molecules Mpro clinical use, we...

AbstractTuberculosis continues to be a global health threat. Pyrazinamide (PZA) is an important first-line drug in multidrug-resistant tuberculosis treatment. The emergence of strains resistant PZA represents public problem, as both first- and second-line treatment regimens include PZA. It becomes toxic Mycobacterium when converted pyrazinoic acid by the bacterial pyrazinamidase (PncA) enzyme. Resistance caused mainly loss enzyme activity mutation, mechanism resistance not completely...

Abstract BCR‐ABL protein is one of the most potent target to treat chronic myeloid leukemia (CML). Apart from other mutations, T315I especially challenging as it confers resistance all first‐ and second‐generation tyrosine kinase inhibitors. So, a thorough study altered behavior upon mutation crucially needed. To understand mechanism mutant protein, we organized long‐term molecular dynamics simulation (500 ns) performed detailed comparative conformational analysis. We found that due at 315th...

Arginine to histidine mutation at position 132 (R132H) in isocitrate dehydrogenase 1 (IDH1) led reduced affinity of the respective enzymes for and increased α-ketoglutarate (AKG) NADPH. This phenomenon retarded oxidative decarboxylation AKG conferred a novel enzymatic activity that facilitated reduction d-2-hydroxyglutarate (d-2HG). The loss utilization gain 2HG production from IDH1 R132H had been taken up as fundamental problem solve this, structural biology approaches were adopted....

A point mutation (P29S) in the RAS-related C3 botulinum toxin substrate 1 (RAC1) was considered to be a trigger for melanoma, form of skin cancer with highest mortality rate. In this study, we have investigated pathogenic role P29S based on conformational behavior RAC1 protein toward guanosine triphosphate (GTP). Molecular interaction, molecular dynamics trajectory analysis (RMSD, RMSF, Rg, SASA, DSSP, and PCA), shape binding pocket were performed analyze interaction energy dynamic native...

Ras-related C3 botulinum toxin substrate 1 (RAC1) is a plasma membrane-associated small GTPase which cycles between the active GTP-bound and inactive GDP-bound states. There wide range of evidences indicating its participation in inducing cancer-associated phenotypes. RAC1 F28L mutation (RAC(F28L)) fast recycling has been implicated several cancer associated cases. In this work we have performed molecular docking dynamics simulation (~0.3 μs) to investigate conformational changes occurring...

Drug resistant mutations have severely restricted the success of HIV therapy. These frequently involve aspartic protease encoded by virus. Knowledge molecular mechanisms underlying conformational changes HIV-1 mutants may be useful in developing more effective and longer lasting treatment regimes. The flap regions are target a particular type occurring far from active site, which able to produce significant resistance against anti-HIV drug TMC-114. We provide insight into basis TMC-114 major...

Abstract Luminescent vibriosis is a major bacterial disease in shrimp hatcheries and causes up to 100% mortality larval stages of penaeid shrimps. We investigated the virulence factors genetic identity 29 luminescent Vibrio isolates from Indian farms, which were earlier presumed as harveyi . Haemolysin gene-based species-specific multiplex PCR phylogenetic analysis rpoD toxR identified all V. campbellii The gene-specific revealed presence markers involved quorum sensing ( luxM , luxS, cqsA...

Human STIL (SCL/TAL1 interrupting locus) protein maintains centriole stability and spindle pole localisation. It helps in recruitment of CENPJ (Centromere J)/CPAP (centrosomal P4.1-associated protein) other centrosomal proteins. Mutations are reported several disorders, especially deregulation cell cycle cascades. In this work, we examined the non-synonymous single nucleotide polymorphisms (nsSNPs) for their disease association. Different SNP prediction tools were used to predict...

Amyotrophic lateral sclerosis 6 (ALS6) is an autosomal recessive disorder caused by heterozygous mutation in the Fused Sarcoma (FUS) gene. ALS6 a neurodegenerative disorder, which affects upper and lower motor neurons brain spinal cord, resulting fatal paralysis. genetic proline/tyrosine-nuclear localization signals of sarcoma Protein (FUS). FUS gene also known as TLS (Translocated liposarcoma), encodes protein called RNA-binding protein-Fus (FUS), has molecular weight 75 kDa. In this...

Genetic variations in oncogenes can often promote uncontrolled cell proliferation by altering the structure of encoded protein, thereby its function. The PI3KCA oncogene that encodes for p110α, catalytic subunit phosphatidylinositol 3-kinase (PI3K), is one most frequently mutated humans. PI3K plays a pivotal role division. consists two subunits: (p110α) and regulatory (p85α). usually controls switches off enzyme when not required. It believed mutations gene alter control p85α over p110α...

AbstractCK1δ (Casein kinase I isoform delta) is a member of CK1 family protein that mediates neurite outgrowth and the function as brain-specific microtubule-associated protein. ATP binding domain CK1δ essential for regulating several key cell cycle signal transduction pathways. Mutation in reported to cause cancers affects normal brain development. S97C mutation has been involved induce breast cancer ductal carcinoma. We performed molecular docking studies examine effect this on its...

Neuronal ceroid-lipofuscinosis (NCL) is a heterogeneous and rare lysosomal storage disorder characterized by the accumulation of autofluorescent materials—ceroid lipofuscin—in cytoplasm.1 It manifested as progressive destruction neuronal cells resulting in brain atrophy, loss vision, other neurodegenerative phenotypes.1 Over 446 mutations different genes have been cataloged NCL mutation database ([ucl.ac.uk/ncl/mutation][1]). The overlapping phenotypes involvement multiple indicate...