<i>In-silico</i> profiling and structural insights into the impact of nSNPs in the <i>P. falciparum acetyl-CoA transporter</i> gene to understand the mechanism of drug resistance in malaria

Sardar, Rahila; Katyal, Nidhi; Ahamad, Shahzaib; Jade, Dhananjay; Ali, Shakir; Gupta, Dinesh

doi:10.1080/07391102.2020.1711807

Cited by 4 publications

(4 citation statements)

References 55 publications

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“…With the advancement of sequencing technology, annotation of the malaria parasite genome has promoted the discovery of various new drugs or vaccine development (Kissinger et al, 2002;Bahl et al, 2003). For example, based on proteomics and genomics, new technologies have been developed to understand the disease resistance mechanism of malaria parasites (Sardar et al, 2021;Sourabh et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

“…With the emerging sequencing technologies, various efforts were facilitated by annotating the Plasmodium genome (Kissinger et al, 2002;Bahl et al, 2003). Multiple studies based on proteome and genome were conducted to develop novel technologies to understand diseaseresistance mechanisms in Plasmodium (Sardar et al, 2021;Sourabh et al, 2021). While the advancement of sequencing technologies are highly bene cial to understand speci c pathways and mechanism related to the disease, the most undesirable aspect for any newly sequenced genome is when almost half of the annotated proteins or genes are in the uncharacterized category.…”

Section: Introductionmentioning

confidence: 99%

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Genome-wide in silico analysis for novel regulators of gametocyte development critical for transmission of Plasmodium falciparum

2023

Trop Biomed

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Malaria, caused by the unicellular Apicomplexan protozoa of the genus Plasmodium, is an infectious disease transmitted via female Anopheles mosquitoes. The sexual stage (gametocytes) of malaria parasites is the key to the transmission of parasites from vertebrate hosts to mosquitoes, representing critical bottleneck of the parasite life cycle. This study has established a systematic computational pipeline to achieve the genome-wide in silico analysis and find 708 novels potentially indispensable genes for gametocyte development, consisting of 644 protein coding genes, 56 ncRNA genes and 8 pseudogenes, with a total of 191 genes in the transmembrane, 29 protein coding genes to be exported proteins, and 58 genes in apicoplast regions. Furthermore, Gene Ontology analysis showed that the largest cluster was cellular processes with nucleus and cytosol highest, followed by molecular function with binding and oxidoreductase activities abundant. Meanwhile, when a text searched, using PlasmoDB, there were 300 genes with annotations of "putative", and 196 genes with annotations of "unknown function". These data would be helpful to provide potential targets for effective malaria transmission-blocking strategies.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Genome-wide in silico analysis for novel regulators of gametocyte development critical for transmission of Plasmodium falciparum

2023

Trop Biomed

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“…With the emerging sequencing technologies, various efforts were facilitated by annotating the Plasmodium genome ( Kissinger et al, 2002 ; Bahl et al, 2003 ). Multiple studies based on proteome and genome were conducted to develop novel technologies to understand disease-resistance mechanisms in Plasmodium ( Sardar et al, 2021 ; Sourabh et al, 2021 ). While the advancement of sequencing technologies are highly beneficial to understand specific pathways and mechanism related to the disease, the most undesirable aspect for any newly sequenced genome is when almost half of the annotated proteins or genes are in the uncharacterized category and annotated as “Hypothetical proteins (HPs)” ( Galperin and Koonin, 2004 ; Singh et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

In-Silico Functional Annotation of Plasmodium falciparum Hypothetical Proteins to Identify Novel Drug Targets

Singh

Gupta

2022

Front. Genet.

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Plasmodium falciparum is one of the plasmodium species responsible for the majority of life-threatening malaria cases. The current antimalarial therapies are becoming less effective due to growing drug resistance, leading to the urgent requirement for alternative and more effective antimalarial drugs or vaccines. To facilitate the novel drug discovery or vaccine development efforts, recent advances in sequencing technologies provide valuable information about the whole genome of the parasite, yet a lot more needs to be deciphered due to its incomplete proteome annotation. Surprisingly, out of the 5,389 proteins currently annotated in the Plasmodium falciparum 3D7 strain, 1,626 proteins (∼30% data) are annotated as hypothetical proteins. In parasite genomic studies, the challenge to annotate hypothetical proteins is often ignored, which may obscure the crucial information related to the pathogenicity of the parasite. In this study, we attempt to characterize hypothetical proteins of the parasite to identify novel drug targets using a computational pipeline. The study reveals that out of the overall pool of the hypothetical proteins, 266 proteins have conserved functional signatures. Furthermore, the pathway analysis of these proteins revealed that 23 proteins have an essential role in various biochemical, signalling and metabolic pathways. Additionally, all the proteins (266) were subjected to computational structure analysis. We could successfully model 11 proteins. We validated and checked the structural stability of the models by performing molecular dynamics simulation. Interestingly, eight proteins show stable conformations, and seven proteins are specific for Plasmodium falciparum, based on homology analysis. Lastly, mapping the seven shortlisted hypothetical proteins on the Plasmodium falciparum protein-protein interaction network revealed 3,299 nodes and 2,750,692 edges. Our study revealed interesting functional details of seven hypothetical proteins of the parasite, which help learn more about the less-studied molecules and their interactions, providing valuable clues to unravel the role of these proteins via future experimental validation.

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“…Mosquito genome annotation helps in various efforts initiative to control malaria infection [16,1] . There are numerous studies has been conducted based on the proteome and genome to develop new malaria-fighting technology [28,29] . Advancement in the sequencing technology enhances the knowledge about pathway and mechanism of targeted diseases.…”

Section: Introductionmentioning

confidence: 99%

In-silico characterization and evolutionary analysis of conserved GPI-anchored protein SGU (Secretory Glycoconjugate of Unknownfunction) in Anopheles gambiae

Singh¹,

Kirar²,

Sehrawat³

2022

Int. J. Mosq. Res.

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To control malaria, researchers are focused on immunogenic protein to develop a vaccine against this life-threatening disease. The target immunogenic proteins against parasite infection and other diseases are mostly focused on GPI-anchor proteins. AgSGU is secretory glycoconjugate, the second most expressed protein in mosquito midgut after blood feeding. Recent studies confirmed that Pfs47 is the key protein for ookinetes invasion in the mosquito midgut and AGAP006398 act as a receptor for Pfs47. Protein interaction pathway analysis using bioinformatics approaches shows that AgSGU makes a complex with AGAP006398 and Pfs47, so here we target AgSGU protein for its functional and molecular characterization. Blastp analysis showing its conservancy in most Anopheles mosquito species. Phylogenetic evolutionary analysis shows that AgSGU is an independently evolved protein and closely related to ACON000570 in Anopheles coluzzii. Domain architecture analysis results that it is composed of a single MBF2 domain which acts as a transcriptional activator factor. The 3-D structure was prepared by I-TASSER and refined with the Galaxy Refine tool. The calculated RMSD value for the predicted structure was 0.558, suggesting the reliability of the 3-D structure. AgSGU was docked with AGAP006398 and Pfs47 and interacted effectively with both the protein. The antigenicity evaluation confirmed its potential to activate the immune response. The C-ImmSim immune response analysis proved that AgSGU protein activates both humoral and acquired immune responses. Finally, these studies conclude that AgSGU protein is a potential target for developing a transmission-blocking vaccine against malaria.

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In-silico profiling and structural insights into the impact of nSNPs in the P. falciparum acetyl-CoA transporter gene to understand the mechanism of drug resistance in malaria

Cited by 4 publications

References 55 publications

Genome-wide in silico analysis for novel regulators of gametocyte development critical for transmission of Plasmodium falciparum

Genome-wide in silico analysis for novel regulators of gametocyte development critical for transmission of Plasmodium falciparum

In-Silico Functional Annotation of Plasmodium falciparum Hypothetical Proteins to Identify Novel Drug Targets

In-silico characterization and evolutionary analysis of conserved GPI-anchored protein SGU (Secretory Glycoconjugate of Unknownfunction) in Anopheles gambiae

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