Molecular insights of newly identified potential peptide inhibitors of hypoxia inducible factor 1α causing breast cancer

Manimaran, D; Ghanendra, Shanmugam; Sridhar, Menakha; Kaliaperumal, Jagatheesh; Muniyaraj, Sangeetha; Mohankumar, Thangavel; Vijayakumar, Rajendran; Krishnan, Manigandan; Balakrishnan, Rengasamy; Elangovan, Namasivayam

doi:10.1016/j.molstruc.2018.09.072

Cited by 6 publications

(7 citation statements)

References 24 publications

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“…having a peptide sequence KAKLF) displayed the highest interaction energy score of − 4.81 kcal/mol with the HIF-1α receptor. These results indicated that peptide ID: 10 as derived from this study is a promising ACP with promising potential against breast cancer when compared to peptide ID: 10 as proposed by the previous study 60 . However, additional in vitro and in vivo approaches will be needed for further development of novel ACPs against breast cancer.…”

Section: Resultssupporting

confidence: 61%

“…We noticed that scores for the top 20 ACPs with the highest ACP scores (S(P)) were in ranges of 636.59–700.64 whereby the threshold value was 311 (Table 1 ). Interestingly, the peptide sequence of KAKLF having an ACP score of 645 was found in the top 9 peptides having a high docking score of -29.75 kJ/mol towards the hypoxia inducible factor 1α (HIF-1α) as reported in the previous study 60 .…”

Section: Resultssupporting

confidence: 57%

“…As seen from Table 5 , the interaction energies of ACPs ID: 21–29 are ranging from − 4.81 kcal/mol to 11.98 kcal/mol. Amongst the 9 ACPs as reported by a previous study 60 , peptide ID: 25 (i.e. having a peptide sequence KAKLF) displayed the highest interaction energy score of − 4.81 kcal/mol with the HIF-1α receptor.…”

Section: Resultsmentioning

confidence: 62%

“…Inspired by this study 60 , the top 20 ACPs (ID: 1-20) derived from the iACP-FSCM were then docked with the predicted binding sites of HIF-1α in order to estimate their interaction energies (kcal/mol) for finding a new www.nature.com/scientificreports/ potential peptide-based drug for HIF-1α. In order to make a fair comparison, the same experimental setup was used for estimating interaction energies of the top 9 ACPs as proposed by the previous study 60 . In this study, HIF-1α was prepared for docking using the protein preparation features in the Chimera software, which was performed using the default protocol for PDB2PQR and Dock Prep.…”

Section: Characterization Of Anticancer Activities Of Peptides Using mentioning

confidence: 99%

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Improved prediction and characterization of anticancer activities of peptides using a novel flexible scoring card method

Charoenkwan

Chiangjong

Lee

et al. 2021

Sci Rep

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As anticancer peptides (ACPs) have attracted great interest for cancer treatment, several approaches based on machine learning have been proposed for ACP identification. Although existing methods have afforded high prediction accuracies, however such models are using a large number of descriptors together with complex ensemble approaches that consequently leads to low interpretability and thus poses a challenge for biologists and biochemists. Therefore, it is desirable to develop a simple, interpretable and efficient predictor for accurate ACP identification as well as providing the means for the rational design of new anticancer peptides with promising potential for clinical application. Herein, we propose a novel flexible scoring card method (FSCM) making use of propensity scores of local and global sequential information for the development of a sequence-based ACP predictor (named iACP-FSCM) for improving the prediction accuracy and model interpretability. To the best of our knowledge, iACP-FSCM represents the first sequence-based ACP predictor for rationalizing an in-depth understanding into the molecular basis for the enhancement of anticancer activities of peptides via the use of FSCM-derived propensity scores. The independent testing results showed that the iACP-FSCM provided accuracies of 0.825 and 0.910 as evaluated on the main and alternative datasets, respectively. Results from comparative benchmarking demonstrated that iACP-FSCM could outperform seven other existing ACP predictors with marked improvements of 7% and 17% for accuracy and MCC, respectively, on the main dataset. Furthermore, the iACP-FSCM (0.910) achieved very comparable results to that of the state-of-the-art ensemble model AntiCP2.0 (0.920) as evaluated on the alternative dataset. Comparative results demonstrated that iACP-FSCM was the most suitable choice for ACP identification and characterization considering its simplicity, interpretability and generalizability. It is highly anticipated that the iACP-FSCM may be a robust tool for the rapid screening and identification of promising ACPs for clinical use.

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Section: Resultssupporting

confidence: 61%

Section: Resultssupporting

confidence: 57%

Section: Resultsmentioning

confidence: 62%

Section: Characterization Of Anticancer Activities Of Peptides Using mentioning

confidence: 99%

See 2 more Smart Citations

Improved prediction and characterization of anticancer activities of peptides using a novel flexible scoring card method

Charoenkwan

Chiangjong

Lee

et al. 2021

Sci Rep

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“…A binding energy value of −5.557 kcal/mol in the optimal spatial structure (Figure 8a) was shown by the presence of the hydrogen bond, such that LSGYGP has a strong affinity toward NF-κB. Hydrophobic interactions have been regarded as the most important non-covalent force in the literature, and have been shown to be responsible for multiple phenomena, including the binding of enzymes to substrates, folding of proteins, and structure stabilization of proteins [47]. In the LSGYGP–NF-κB interaction, most of the amino acid interactions are attributed to the hydrophobic amino acids of LSGYGP.…”

Section: Discussionmentioning

confidence: 99%

In Vitro Vascular-Protective Effects of a Tilapia By-Product Oligopeptide on Angiotensin II-Induced Hypertensive Endothelial Injury in HUVEC by Nrf2/NF-κB Pathways

et al. 2019

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Angiotensin II (Ang II) is closely involved in endothelial injury during the development of hypertension. In this study, the protective effects of the tilapia by-product oligopeptide Leu-Ser-Gly-Tyr-Gly-Pro (LSGYGP) on oxidative stress and endothelial injury in Angiotensin II (Ang II)-stimulated human umbilical vein endothelial cells (HUVEC) were evaluated. LSGYGP dose-dependently suppressed the fluorescence intensities of nitric oxide (NO) and reactive oxygen species (ROS), inhibited the nuclear factor-kappa B (NF-κB) pathway, and reduced inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and endothelin-1 (ET-1) expression, as shown by western blot. In addition, it attenuated the expression of gamma-glutamyltransferase (GGT) and heme oxygenase 1 (HO-1), as well as increasing superoxide dismutase (SOD) and glutathione (GSH) expression through the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. Other experiments revealed that LSGYGP increased the apoptotic inhibition ratio between cleaved-caspase-3/procaspase-3, reduced expressions of pro-apoptotic ratio between Bcl-2/Bax, inhibited phosphorylation of mitogen-activated protein kinases (MAPK), and increased phosphorylation of the serine/threonine kinase (Akt) pathway. Furthermore, LSGYGP significantly decreased Ang II-induced DNA damage in a comet assay, and molecular docking results showed that the steady interaction between LSGYGP with NF-κB may be attributed to hydrogen bonds. These results suggest that this oligopeptide is effective in protecting against Ang II-induced HUVEC injury through the reduction of oxidative stress and alleviating endothelial damage. Thus, it has the potential for the therapeutic treatment of hypertension-associated diseases.

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Application of molecular docking in elaborating molecular mechanisms and interactions of supramolecular cyclodextrin

Guo

Zong

et al. 2022

Carbohydrate Polymers

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Molecular insights of newly identified potential peptide inhibitors of hypoxia inducible factor 1α causing breast cancer

Cited by 6 publications

References 24 publications

Improved prediction and characterization of anticancer activities of peptides using a novel flexible scoring card method

Improved prediction and characterization of anticancer activities of peptides using a novel flexible scoring card method

In Vitro Vascular-Protective Effects of a Tilapia By-Product Oligopeptide on Angiotensin II-Induced Hypertensive Endothelial Injury in HUVEC by Nrf2/NF-κB Pathways

Application of molecular docking in elaborating molecular mechanisms and interactions of supramolecular cyclodextrin

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