scholarly journals Structural and Functional Annotation of Hypothetical Protein AVO28_00330 of Yersinia pestis: An In Silico Approach

2021 ◽  
Author(s):  
Sunzid Ahmed
Keyword(s):  
Yersinia Pestis ◽  
In Silico ◽  
Interaction Analysis ◽  
3D Structure ◽  
In Silico Analysis ◽  
Hypothetical Protein ◽  
Therapeutic Drug ◽  
Outer Cell ◽  
Hypothetical Proteins ◽  
Metal Binding Domain

Yersinia pestis is an infamous gram-negative, coccobacillus enterobacterium responsible for three devastating plague pandemics worldwide. The recent outbreak of this zoonotic disease demands in silico study of the hypothetical proteins for efficient drug and vaccine discovery. As hypothetical proteins constitute a substantial portion of the proteome, it’s essential to annotate them structurally and functionally. The current study characterized physicochemical properties, predicted homology-based 3D structure and annotated functions of the hypothetical protein AVO28_00330 of Y. pestis using a range of bioinformatic tools and softwares. Swiss Model and Phyre2 server were utilized to predict the tertiary model which was minimized energetically using YASARA server. The quality assessment servers found the model as a good one. For future molecular docking analysis, active binding sites were predicted using CASTp. Protein-protein interaction analysis was performed in STRING server. For functional prediction InterPro, Pfam, Motif and other tools were used. The hypothetical protein revealed tricopeptide repeat domain and rubredoxin metal-binding domain which regulates lipopolysaccharide metabolic process in the outer cell membrane which contributes to virulence property of the protein. Therefore, this in silico analysis will improve the current understanding of the protein and aid in the future analysis regarding therapeutic drug and vaccine investigation.

scholarly journals Identifying new COVID-19 receptor Neuropilin-1 in severe Alzheimer’s diseases patients group brain using genome-wide association study approach

2021 ◽  
Author(s):  
Key-Hwan Lim ◽  
Sumin Yang ◽  
Sung-Hyun Kim ◽  
Jae-Yeol Joo
Keyword(s):  
In Silico ◽  
Genome Wide Association Study ◽  
Transmembrane Protein ◽  
In Silico Analysis ◽  
Therapeutic Drug ◽  
Rna Seq ◽  
Total Rna ◽  
Neuropilin 1 ◽  
Silico Analysis ◽  
Brain Tissues

Abstract Background Numerous studies have been conducted on different aspects of the COVID-19 (coronavirus disease 2019) pandemic, which is caused by SARS-CoV-2, since its emergence in late 2019. Mutual relations among SARS-CoV-2 and neuro-pathophysiological phenomena are continuously being demonstrated, and several underlying diseases, such as those in the elderly, are positively correlated with susceptibility to SARS-CoV-2 infection. The expression of angiotensin converting enzyme 2 (ACE2), which is required for SARS-CoV-2 infection, was recently demonstrated to be increased in Alzheimer’s disease (AD) patients. Methods Recent preclinical studies have shown that Neuropilin-1 (NRP1), which is a transmembrane protein with roles in neuronal development, axonal outgrowth, and angiogenesis, also plays a role in the infectivity of SARS-CoV-2. Thus, we hypothesized that NRP1 may be upregulated in AD patients and that a correlation between AD and SARS-CoV-2 NRP1-mediated infectivity may exist. We used an AD mouse model that mimics AD and performed high throughput total RNA-seq with brain tissue and whole blood. For quantification of NPR1 in AD, brain tissues and blood were subjected to western blotting and RT-qPCR analysis. In silico analysis for NRP1 expression in AD patients has been performed on the human hippocampus data sets (GSE4226, GSE1297). Results Many cases of severe symptom of COVID-19 are concentrated in elderly group who have complications such as diabetes, degenerative disease, and brain disorders. Total RNA-seq analysis showed that Nrp1 gene was commonly overexpressed in AD model. Similar to ACE2, NRP1 protein also strongly expressed in the AD brain tissues. Interestingly, in silico analysis revealed that the level of expression for NRP1 was distinct at age and AD progression. Conclusions Given that the NRP1 is highly expressed in AD, it will be important to understand and predict that NRP1 may a risk factor for SARS-CoV-2 infection in AD patients. This will support to development of potential therapeutic drug to reduce SARS-CoV-2 transmission.

In-Silico Analysis to Identify Potential Inhibitors Against the Protein NSP12 of SARS-CoV-2

2021 ◽  
Vol 6 (3) ◽  
pp. 48-60
Author(s):  
Hima Vyshnavi ◽  
Gayathri S. S. ◽  
Shahanas Naisam ◽  
Suvanish Kumar ◽  
Nidhin Sreekumar
Keyword(s):  
In Silico ◽  
Interaction Analysis ◽  
In Silico Analysis ◽  
Drug Efficacy ◽  
Drug Candidate ◽  
In Vivo Analysis ◽  
The Stability ◽  
Potential Inhibitors ◽  
Silico Analysis

In this pandemic condition, a drug candidate which is effective against COVID-19 is very much desired. This study initiates an in silico analysis to screen small molecules such as phytochemicals, drug metabolites, and natural metabolites against Nsp12 (a catalytic unit for RNA transcription and replication). Molecular interaction analysis of 6M71 was carried out against 2,860 ligands using Schrodinger Glide software. After docking analysis, the top 10 molecules (Glide score) were subjected to MD simulation for validating the stability. It resulted in top 10 compounds with high binding affinities with the target molecule NSP 12. Out of these, top 3 compounds including PSID_08_LIG3 (HMDB0133544), PSID_08_LIG4 (HMDB0132898), and PSID_08_LIG9 (HMDB0128199) show better Glide scores, better H-bond interaction, better MMGBSA value and stability on dynamic simulation after analysis of the results. The suggested ligands can be postulated as effective antiviral drugs against COVID-19. Further in vivo analysis is needed for validating the drug efficacy.

scholarly journals In Silico Evaluation of Interactions of Triterpenes in Momordica charantia on Proteins Involved in Angiogenesis

Proceedings ◽  
2019 ◽  
Vol 40 (1) ◽  
pp. 2
Author(s):  
Büşra Sevim ◽  
Onur Eroğlu
Keyword(s):  
In Silico ◽  
3D Structure ◽  
In Silico Analysis ◽  
Active Role ◽  
Docking Studies ◽  
Momordica Charantia ◽  
Tyrosine Kinase Receptor ◽  
X Ray Diffraction ◽  
Aggressive Cancer

Angiogenesis is important process that play active role in tumorigenesis. VEGFR-1, a member of the tyrosine kinase receptor family, is known as the receptor for VEGF ligands in tumor cells. SPARC protein has recently been shown to play a role in metastasis in various types of cancer. Momordica charantia; is a valuable plant used quite often in traditional medicine. Triterpenes from that plant appear to be promising in in vitro cancer studies. In this study; triterpenes in fruit and seed of M. charantia were selected according to literature. The 3D structure files of triterpenes were obtained from PubChem. The structure files of ligands were prepared with various programs and converted to the appropriate file format. X-ray diffraction structure files of proteins were obtained from RCSB PDB. These structure files were made suitable for molecular docking studies. Docking was performed with the AutoDock Tool (downloaded from autodock.scripps.edu/resources/adt), and the results were scored using the Vina program. According to the in silico analysis; It has been found that various triterpenes which can be obtained from M. charantia can co-inhibit VEGFR-1 and SPARC proteins. These results show that these triterpenes are promising in terms of new therapeutic routes for aggressive cancer therapy.

scholarly journals In Silico identification of potential drug targets by subtractive genome analysis of Enterococcus faecium DO

2020 ◽  
Author(s):  
Marwah Karim ◽  
MD Nazrul Islam ◽  
G. M. Nurnabi Azad Jewel
Keyword(s):  
Alcohol Dehydrogenase ◽  
Enterococcus Faecium ◽  
In Silico ◽  
Drug Targets ◽  
3D Structure ◽  
Comparative Genomic ◽  
Therapeutic Drug ◽  
Potential Drug ◽  
Novel Drug ◽  
Potential Drug Targets

AbstractOnce believed to be a commensal bacteria, Enterococcus faecium has recently emerged as an important nosocomial pathogen worldwide. A recent outbreak of E. faecium unrevealed natural and in vitro resistance against a myriad of antibiotics namely ampicillin, gentamicin and vancomycin due to over-exposure of the pathogen to these antibiotics. This fact combined with the ongoing threat demands the identification of new therapeutic targets to combat E. faecium infections.In this present study, comparative proteome analysis, subtractive genomic approach, metabolic pathway analysis and additional drug prioritizing parameters were used to propose a potential novel drug targets for E. faecium strain DO. Comparative genomic analysis of Kyoto Encyclopedia of Genes and Genomes annotated metabolic pathways identified a total of 207 putative target proteins in E. faecium DO that showed no similarity to human proteins. Among them 105 proteins were identified as essential novel proteins that could serve as potential drug targets through further bioinformatic approaches; such as-prediction of subcellular localization, calculation of molecular weight, and web-based investigation of 3D structural characterization. Eventually 19 non-homologous essential proteins of E. faecium DO were prioritized and proved to have the eligibility to become novel broad-spectrum antibiotic targets. Among these targets aldehyde-alcohol dehydrogenase was found to be involved in maximum pathways, and therefore, was chosen as novel drug target. Interestingly, aldehyde-alcohol dehydrogenase enzyme contains two domains namely acetaldehyde dehydrogenase and alcohol dehydrogenase, on which a 3D structure homology modeling and in silico molecular docking were performed. Finally, eight molecules were confirmed as the most suitable ligands for aldehyde-alcohol dehydrogenase and hence proposed as the potential inhibitors of this target.In conclusion, being human non-homologous, aldehyde-alcohol dehydrogenase protein can be targeted for potential therapeutic drug development in future. However, laboratory based experimental research should be performed to validate our findings in vivo.

scholarly journals Identifying new COVID-19 receptor Neuropilin-1 in severe Alzheimer’s diseases patients group brain using genome-wide association study approach

2021 ◽  
Author(s):  
Key-Hwan Lim ◽  
Sumin Yang ◽  
Sung-Hyun Kim ◽  
Jae-Yeol Joo
Keyword(s):  
In Silico ◽  
Genome Wide Association Study ◽  
Transmembrane Protein ◽  
In Silico Analysis ◽  
Therapeutic Drug ◽  
Rna Seq ◽  
Total Rna ◽  
Neuropilin 1 ◽  
Silico Analysis ◽  
Brain Tissues

Abstract Background Numerous studies have been conducted on different aspects of the COVID-19 (coronavirus disease 2019) pandemic, which is caused by SARS-CoV-2, since its emergence in late 2019. Mutual relations among SARS-CoV-2 and neuro-pathophysiological phenomena are continuously being demonstrated, and several underlying diseases, such as those in the elderly, are positively correlated with susceptibility to SARS-CoV-2 infection. The expression of angiotensin converting enzyme 2 (ACE2), which is required for SARS-CoV-2 infection, was recently demonstrated to be increased in Alzheimer’s disease (AD) patients.Methods Recent preclinical studies have shown that Neuropilin-1 (NRP1), which is a transmembrane protein with roles in neuronal development, axonal outgrowth, and angiogenesis, also plays a role in the infectivity of SARS-CoV-2. Thus, we hypothesized that NRP1 may be upregulated in AD patients and that a correlation between AD and SARS-CoV-2 NRP1-mediated infectivity may exist. We used an AD mouse model that mimics AD and performed high throughput total RNA-seq with brain tissue and whole blood. For quantification of NPR1 in AD, brain tissues and blood were subjected to western blotting and RT-qPCR analysis. In silico analysis for NRP1 expression in AD patients has been performed on the human hippocampus data sets (GSE4226, GSE1297).Results Many cases of severe symptom of COVID-19 are concentrated in elderly group who have complications such as diabetes, degenerative disease, and brain disorders. Total RNA-seq analysis showed that Nrp1 gene was commonly overexpressed in AD model. Similar to ACE2, NRP1 protein also strongly expressed in the AD brain tissues. Interestingly, in silico analysis revealed that the level of expression for NRP1 was distinct at age and AD progression.Conclusions Given that the NRP1 is highly expressed in AD, it will be important to understand and predict that NRP1 may a risk factor for SARS-CoV-2 infection in AD patients. This will support to development of potential therapeutic drug to reduce SARS-CoV-2 transmission.

In Silico Analysis for Determination and Validation of Human CD20 Antigen 3D Structure

2017 ◽  
Vol 25 (1) ◽  
pp. 123-135 ◽  
Author(s):  
Zahra Payandeh ◽  
Masoumeh Rajabibazl ◽  
Yousef Mortazavi ◽  
Azam Rahimpour
Keyword(s):  
In Silico ◽  
3D Structure ◽  
In Silico Analysis ◽  
Cd20 Antigen ◽  
Silico Analysis

scholarly journals In Silico Analysis Predicting Effects of Deleterious SNPs of Human RASSF5 Gene on its Structure and Functions

2020 ◽  
Author(s):  
Md. Shahadat Hossain ◽  
Arpita Singha Roy ◽  
Md. Sajedul Islam
Keyword(s):  
Protein Interactions ◽  
In Silico ◽  
Structural Changes ◽  
Interaction Analysis ◽  
In Silico Analysis ◽  
Therapeutic Interventions ◽  
Protein Protein Interactions ◽  
Post Translational Modification ◽  
Protein Protein Interaction ◽  
The Stability

AbstractRas association domain-containing protein 5 (RASSF5), one of the prospective biomarkers for tumors, generally plays a crucial role as a tumor suppressor. As deleterious effects can result from functional differences through SNPs, we sought to analyze the most deleterious SNPs of RASSF5 as well as predict the structural changes associated with the mutants that hamper the normal protein-protein interactions. We adopted both sequence and structure based approaches to analyze the SNPs of RASSF5 protein. We also analyzed the putative post translational modification sites as well as the altered protein-protein interactions that encompass various cascades of signals. Out of all the SNPs obtained from the NCBI database, only 25 were considered as highly deleterious by six in silico SNP prediction tools. Among them, upon analyzing the effect of these nsSNPs on the stability of the protein, we found 17 SNPs that decrease the stability. Significant deviation in the energy minimization score was observed in P350R, F321L, and R277W. Besides this, docking analysis confirmed that P350R, A319V, F321L, and R277W reduce the binding affinity of the protein with H-Ras, where P350R shows the most remarkable deviation. Protein-protein interaction analysis revealed that RASSF5 acts as a hub connecting two clusters consisting of 18 proteins and alteration in the RASSF5 may lead to disassociation of several signal cascades. Thus, based on these analyses, our study suggests that the reported functional SNPs may serve as potential targets for different proteomic studies, diagnosis and therapeutic interventions.

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