- HIV Research and Treatment
- Glycosylation and Glycoproteins Research
- Monoclonal and Polyclonal Antibodies Research
- RNA and protein synthesis mechanisms
- Peptidase Inhibition and Analysis
- Machine Learning in Bioinformatics
- Bacteriophages and microbial interactions
- Galectins and Cancer Biology
- Neonatal Respiratory Health Research
- Viral Infections and Outbreaks Research
- Protease and Inhibitor Mechanisms
- Genomics and Chromatin Dynamics
- IoT and Edge/Fog Computing
- vaccines and immunoinformatics approaches
- Signaling Pathways in Disease
- T-cell and B-cell Immunology
- Neuropeptides and Animal Physiology
- Cloud Computing and Resource Management
- Alzheimer's disease research and treatments
- Virology and Viral Diseases
- HIV/AIDS drug development and treatment
- Biochemical and Structural Characterization
- Genetic Neurodegenerative Diseases
- Immune Cell Function and Interaction
- Redox biology and oxidative stress
Central University of South Bihar
2022-2024
Mahatma Gandhi Central University
2022-2024
National Institute of Technology Patna
2024
All India Institute of Medical Sciences Rishikesh
2024
Scripps Research Institute
2016-2023
Indian Institute of Technology BHU
2023
Banaras Hindu University
2023
Shree Guru Gobind Singh Tricentenary University
2022
ICAR-Indian Institute of Maize Research
2022
Kothiwal Dental College and Research Centre
2022
Abstract Stabilized HIV-1 envelope glycoproteins (Env) that resemble the native Env are utilized in vaccination strategies aimed at inducing broadly neutralizing antibodies (bNAbs). To limit exposure of rare isolate-specific antigenic residues/determinants we generated a SOSIP trimer based on consensus sequence all group M isolates (ConM). The ConM displays epitopes most known bNAbs and several germline bNAb precursors. crystal structure 3.9 Å resolution resembles its surface few residues....
Inspection of the naive B cell repertoire specific for an HIV vaccine immunogen provides actionable information human design and advancement.
Overcoming envelope metastability is crucial to trimer-based HIV-1 vaccine design. Here, we present a coherent strategy by minimizing metastability. For 10 strains across five clades, demonstrate that the gp41 ectodomain (gp41ECTO) main source of replacing wild-type gp41ECTO with BG505 uncleaved prefusion-optimized (UFO) These gp41ECTO-swapped trimers can be produced in CHO cells high yield and purity. The crystal structure trimer elucidates how neutralization-resistant tier 3 virus evades...
Targeting germline (gl-) precursors of broadly neutralizing antibodies (bNAbs) is acknowledged as an important strategy for HIV-1 vaccines. The VRC01-class bNAbs attractive because its distinct genetic signature. However, often require extensive somatic hypermutation, including rare insertions and deletions. We describe a BG505 SOSIP trimer, termed GT1.2, to optimize binding gl-CH31, the unmutated common precursor CH30-34 bNAb lineage that acquired large CDRH1 insertion. GT1.2 trimer...
Engineered SOSIP trimers mimic envelope-glycoprotein spikes, which stud the surface of HIV-1 particles and mediate viral entry into cells. When used for immunizing test animals, they elicit antibodies that neutralize resistant sequence-matched isolates. These neutralizing recognize epitopes in holes glycan shield covers trimer. Here, we added glycans to block most immunogenic neutralization on BG505 B41 trimers. In addition, removed selected other open new might expose epitopes. We immunized...
Caspases are enzymes belonging to a conserved family of cysteine-dependent aspartic-specific proteases that involved in vital cellular processes and play prominent role apoptosis inflammation. Determining all relevant protein substrates caspases remains challenging task. Over 1500 caspase have been discovered the human proteome according published data new on daily basis. To aid discovery process we developed cleavage prediction method using recently curated MerCASBA database experimentally...
Skeletal muscle constitutes more than 30% of total body mass using substrates such as glycogen, glucose, free fatty acids, and creatinine phosphate to generate energy. Consequently, multinucleated myofibers resident mononucleated stem cells (satellite cells) several metabolites, which enter into circulation affecting the function other organs, especially during exercise atrophy. The present study was aimed at building a comprehensive profile metabolites in primary human skeletal myogenic...
The fusion peptide (FP) of HIV-1 envelope glycoprotein (Env) is essential for mediating viral entry. Detection broadly neutralizing antibodies (bnAbs) that interact with the FP has revealed it as a site vulnerability. We delineate X-ray and cryo-electron microscopy (cryo-EM) structures bnAb ACS202, from an HIV-infected elite neutralizer, soluble Env trimer (AMC011 SOSIP.v4.2) derived same patient. show ACS202 CDRH3 forms "β strand" interaction exposed hydrophobic recognizes continuous region...
Abstract Ebola virus (EBOV) glycoprotein (GP) can be recognized by neutralizing antibodies (NAbs) and is the main target for vaccine design. Here, we first investigate contribution of stalk heptad repeat 1-C (HR1 C ) regions to GP metastability. Specific HR1 modifications in a mucin-deleted form (GPΔmuc) increase trimer yield, whereas alterations exert more complex effect on thermostability. Crystal structures are determined validate two rationally designed GPΔmuc trimers their unliganded...
CleavPredict (http://cleavpredict.sanfordburnham.org) is a Web server for substrate cleavage prediction matrix metalloproteinases (MMPs). It intended as computational platform aiding the scientific community in reasoning about proteolytic events. offers silico of sites specific 11 human MMPs. The method employs MMP position weight matrices (PWMs) derived from statistical analysis high-throughput phage display experimental results. To augment process, provides information structural features...
Furin cleavage of the HIV envelope glycoprotein is an essential step for cell entry that enables formation well-folded, native-like glycosylated trimers, releases constraints on fusion peptide, and limits enzymatic processing N-glycan shield. Here, we show a cleavage-independent, stabilized, soluble Env trimer mimic (BG505 NFL.664) exhibits "closed-form", native-like, prefusion conformation akin to furin-cleaved trimers. The crystal structure BG505 NFL.664 at 3.39 Å resolution with two...
Abstract The N-terminal fusion peptide (FP) of the human immunodeficiency virus (HIV)-1 envelope glycoprotein (Env) gp41 subunit plays a critical role in cell entry. However, capturing structural flexibility unbound FP is challenging native Env trimer. Here, conformational isomerism observed two crystal structures soluble clade B transmitted/founder B41 SOSIP.664 with broadly neutralizing antibodies (bNAbs) PGT124 and 35O22 to aid crystallization that are not specific for binding FP. Large...
Incessant antigenic evolution enables the persistence and spread of influenza virus in human population. As principal target immune response, hemagglutinin (HA) surface antigen on viruses continuously acquires replaces N-linked glycosylation sites to shield immunogenic protein epitopes using host-derived glycans. Anti-glycan antibodies, such as 2G12, HIV-1 envelope (Env), which is even more extensively glycosylated contains under-processed oligomannose-type clusters its dense glycan shield....
Guanine protein-coupled receptors (GPCRs) constitute a eukaryotic transmembrane protein family and function as "molecular switches" in the second messenger cascades are found all organisms between yeast humans. They form single, biggest drug-target due to their versatility of action role several physiological functions, being active players detecting presence light, variety smells tastes, amino acids, nucleotides, lipids, chemicals etc. environment cell. Comparative genomic studies on model...
Human Galectin-8 (Gal-8) is a member of the galectin family which shares an affinity for β-galactosides. The tandem-repeat Gal-8 consists N- and C-terminal carbohydrate recognition domain (N- C-CRD) joined by linker peptide various length. Despite their structural similarity both CRDs recognize different oligosaccharides. While molecular requirements N-CRD high binding to sulfated sialylated glycans have recently been elucidated crystallographic studies complexes with several...
The computational world has become very large and complex. Cloud is an emerging technology in the of Information Technology. computing offers IT capabilities as services. based services are on demand, scalable, device independent reliable. built virtualization concept. Virtualization separates hardware from software benefits server consolidation live migration. In this paper we present overview cloud also describe about its key "virtualization". We presenting research challenges computing.
BNAbs of V H 1-69 germline origin from a Chinese patient recognize the V3 glycan supersite via disulfide-locked long HCDR3 loop.
Abstract Engineering zinc finger protein motifs for specific DNA targets in genomes is critical the field of genome engineering. We have developed a computational method predicting recognition helices C2H2 fingers that bind to target sites. This prediction based on artificial neural network using an exhaustive dataset proteins and their triplets. Users can select option two or three be predicted either modular synergistic fashion input sequence. would valuable researchers interested...