Homology Model and Docking-Based Virtual Screening for Ligands of Human Dyskerin as New Inhibitors of Telomerase for Cancer Treatment

Armando, Romina; Gómez, Diego Luis Mengual; Juritz, Ezequiel; Menna, Pablo Lorenzano; Gomez, Daniel E.

doi:10.3390/ijms19103216

Cited by 17 publications

(16 citation statements)

References 45 publications

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“…This method has been applied in most proteins to generate new structures from sequences, crucial for protein model design and protein folding. Additionally, this technique has been widely used to analyse protein structures and intermolecular interaction patterns of various proteins [12,13].…”

Section: Introductionmentioning

confidence: 99%

TAF1A and ZBTB41 serve as novel key genes in cervical cancer identified by integrated approaches

et al. 2020

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Cervical cancer (CC) is the second most common cancer and the leading cause of cancer mortality in women. Numerous studies have found that the development of CC was associated with multiple genes. However, the mechanisms on gene level are enigmatic, hindering the understanding of its functional roles. This study sought to identify prognostic biomarkers of CC, and explore their biological functions. Here we conducted an integrated analysis to screen potential vital genes. Candidate genes were further tested by experiments in clinical specimens and cancer cell line. Then, molecular modeling was used to predict the three-dimensional structure of candidate genes’ proteins, and the interaction pattern was analyzed by docking simulation technique. Among the potential genes identified, we found that TAF1A and ZBTB41 were highly correlated. Furthermore, there was a definite interaction between the proteins of TAF1A and ZBTB41, which was affected by the activity of the p53 signaling pathway. In conclusion, our findings identified TAF1A and ZBTB41 could serve as biomarkers of CC. We confirmed their biological function and deciphered their interaction for the first time, which may be helpful for developing further researches.

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Section: Introductionmentioning

confidence: 99%

TAF1A and ZBTB41 serve as novel key genes in cervical cancer identified by integrated approaches

et al. 2020

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“…However, the effects of YBX1 inhibitors on drug resistance in breast cancer require further investigation ( Jiang et al, 2022 ). Three inhibitors were developed based on the interaction between DKC1 and TERC to inhibit telomerase activity in breast cancer cell lines, which may aid in development of pseudouridine synthase inhibitors for treatment of cancer ( Armando et al, 2018 ).…”

Section: Ribonucleic Acid Modifications As Potential Drug Targets In ...mentioning

confidence: 99%

The Key Role of RNA Modification in Breast Cancer

Liu

Zhu

Jiang

et al. 2022

Front. Cell Dev. Biol.

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The modulation of the function and expression of epigenetic regulators of RNA modification has gradually become the hotspot of cancer research. Studies have shown that alteration of epigenetic modifications can promote the development and metastasis of breast cancer. This review highlights the progress in characterization of the link between RNA modification and the prognosis, carcinogenesis and treatment of breast cancer, which may provide a new theoretical basis for development of effective strategies for monitoring of breast cancer based on epigenetics.

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“…Even though docking is widely used as a method of virtual screening (VS), ligand-based approaches could be as effective as docking, , especially when cocrystal structures with good quality three-dimensional coordinates are not available. If one is unable to build a sufficiently good homology model, ligand-based virtual screening remains the only option.…”

Section: Introductionmentioning

confidence: 99%

Indexing Ultrafast Shape-Based Descriptors in MongoDB to Identify TLR4 Pathway Agonists

Polyakov

Alexandrov²,

Maderna

et al. 2022

J. Chem. Inf. Model.

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A method is presented for an ultrafast shape-based search workflow for the screening of large compound collections, i.e., those of vendors. The three-dimensional shape of a molecule dictates its biological activity by enabling the molecule to fit into binding pockets of proteins. Quite often, distinctly different chemical compounds that have similar shapes can bind in a similar way. OpenEye pioneered an algorithm for comparing shapes of molecules by overlaying them in a computer and measuring differences between a query molecule and a target molecule. Overlaying shapes is a computationally intensive process and represents a bottleneck in searching for similar molecules. More recent publications describe alternative methods of overlaying molecules, which are accomplished by comparing shape-based descriptors. These methods were implemented in the Open Drug Discovery Toolkit (ODDT) package. We utilized a combination of open-source software packages like ODDT and RDkit to implement a workflow for ultrafast conformer generation and matching that does not require storing precomputed conformers on the file system or in memory. Moreover, the generated descriptors could be optionally stored in MongoDB for performing searches in the future. To speed up the search, we created a set of indexes from the transformed shape-based descriptors. We are in the process of calculating descriptors for multiple vendors, including Enamine’s “REAL” collection of 1.2 billion compounds. Currently, the shape similarity search on more than 70 million compounds takes less than 8 s! We exemplified our methodology with the screen of compounds that can act as putative TLR4 agonists. The search was based on a literature-known small-molecule TLR4 agonist series. In due course, we identified compounds with novel structural motifs that were active in mouse and human TLR4 reporter cell lines.

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Homology Model and Docking-Based Virtual Screening for Ligands of Human Dyskerin as New Inhibitors of Telomerase for Cancer Treatment

Cited by 17 publications

References 45 publications

TAF1A and ZBTB41 serve as novel key genes in cervical cancer identified by integrated approaches

TAF1A and ZBTB41 serve as novel key genes in cervical cancer identified by integrated approaches

The Key Role of RNA Modification in Breast Cancer

Indexing Ultrafast Shape-Based Descriptors in MongoDB to Identify TLR4 Pathway Agonists

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