ORCID Profile
0000-0003-1214-9374
Current Organisations
Jawaharlal Nehru University
,
Sam Higginbottom Institute of Agriculture Technology and Sciences
,
University of Lucknow
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Publisher: Informa UK Limited
Date: 02-10-2022
DOI: 10.1080/07391102.2022.2120538
Abstract: The protein galectin, which binds to carbohydrates and is involved in a number of therapeutic processes including cell proliferation, inflammatory responses, apoptosis, etc., has been discovered as a potential therapeutic target. Galectin-3 is a stable biomarker that exhibits both increased and decreased expression in a variety of illnesses and infections, regardless of sex, age, or body mass index. The goal of the current study is to apply bioinformatics techniques to examine the possibility of cardiovascular medications to inhibit Galectin-3-related biological activities. Unsupervised clustering techniques, molecular docking, and guided molecular dynamics (MD) simulation were used to create a computational pipeline that was used to screen potential chemical compounds from a library of chemical compounds with related molecular fingerprints. Utilizing input factors such as gene expression, mode of action, and chemical descriptors, clustering enables prioritization of medicinal molecules. Twenty-four compounds were screened and repurposed against Galectin-3 utilizing molecular docking as part of the cluster-facilitated virtual screening technique. The polar interactions that Arg144, Glu184, Arg162, His158, and Asn174 have with Bufalin, Cymarin, and Ouabalin have the highest binding affinities, according to docking studies. Studies using MD simulations confirm the tested compounds' ability to inhibit Galectin-3. Galactin-3 targeted experimental and
Publisher: Future Medicine Ltd
Date: 07-2013
DOI: 10.2217/FNL.13.26
Abstract: Aim: Recent genome-wide association studies have revealed large numbers of single nucleotide polymorphisms (SNPs) related to Alzheimer’s disease. Here, we have investigated the gene CTSB, which plays a crucial role in encoding CTSB, a lysosomal cysteine proteinase protein. CTSB is also involved in the proteolytic processing of amyloid precursor protein (APP), which is believed to be a causative factor in Alzheimer’s disease. Materials & methods: Several bioinformatics algorithms such as, Sorting Intolerant from Tolerant (SIFT), Polymorphism Phenotyping (PolyPhen) and CUPSAT could identify the synonymous SNPs and nonsynonymous SNPs (nsSNPs), which are predicted to be deleterious and nondeleterious, respectively. Similar tools were used to predict the impact of single amino acid substitutions on CTSB protein activity. The FASTSNP server and UTRscan were used to predict the influence on splicing regulations. The stability and solvent-accessible surface area of modeled mutated proteins were analyzed using PBEQ solver and NetASA view. Furthermore, the DSP program was used to determine the secondary structures of the modeled protein. Results: A total of 999 SNPs in CTSB were retrieved from the SNP database 55 nsSNPs, 35 synonymous SNPs, 165 mRNA were found in the 3´untranslated region SNPs, 12 SNPs were found in the 5´untranslated region in addition to 732 intronic SNPs. Potential functions of SNPs in the CTSB gene were identified using different web servers. For ex le, SIFT, PolyPhen and CUPSAT servers predicted ten nsSNPs to be intolerant, three nsSNPs to be damaging and eight nsSNPs to have the potential to destabilize protein structure. The FASTSNP server predicted 12 SNPs to influence splicing regulation, whereas two SNPs could predict a risk in the range of 3–4 (medium to high). Furthermore, mutant proteins were modeled and the total energy values were compared with the native CTSB protein. It was observed that on the surface of the protein, a mutation from threonine to serine at position 235 (rs17573) caused the greatest impact on stability. Conclusion: The genome-wide association studies database has already found rs7003814 of the CTSB gene reported against Alzheimer’s disease. Our study demonstrates the presence of other deleterious nsSNPs, which may play a crucial role in predicting Alzheimer’s disease risk.
Location: India
No related grants have been discovered for Pallavi Somvanshi.