Inverse Molecular Docking Elucidating the Anticarcinogenic Potential of the Hop Natural Product Xanthohumol and Its Metabolites
Abstract
:1. Introduction
2. Materials and Methods
2.1. Inverse Molecular Docking
2.2. Preparation and Execution of Inverse Docking Procedure Using CANDOCK Algorithm
2.3. Method Validation Using Retrospective Metrics
3. Results and Discussion
3.1. Novel Human Protein Targets of Xanthohumol
3.2. Novel Human Protein Targets of Isoxanthohumol, 8-Prenylnaringenin, and 6-Prenylnaringenin
3.3. Method Validation
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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PDB ID with Chain | Protein Name | Predicted Docking Score (arb. Units) * | Protein Function | Anticarcinogenic Function ** | Correlation with Xanthohumol *** |
---|---|---|---|---|---|
5kjkA | N-lysine methyltransferase SMYD2 | −64.79 | Suppresses cell proliferation and directly regulates p53 function [32,33]. | Yes [32] | No |
5synA | Acyl-protein thioesterase 2 | −64.13 | Involved in depalmitoylation [34]. | Yes [34] | No |
3fedA | Glutamate carboxypeptidase III | −62.50 | Involved in a variety of neuropathologies and malignancies such as glutamatergic neurotoxicity and prostate cancer [35]. | Yes [36] | No |
4y30A | Arginine N-methyltransferase 6 | −62.00 | Involved in the regulation of transcription process, signal transduction, human immunodeficiency virus pathogenesis, DNA damage response, and cell cycle progression [37,38,39]. | Yes [38] | No |
4jijA | Matrix metalloproteinase 9 | −59.85 | The main function of MMP-9 is proteolytic activity in the extracellular environment [40,41]. | Yes [40] | Yes [41] |
3e7oA | Mitogen-activated protein kinase 9 | −59.84 | The mitogen-activated protein kinase pathway controls the growth and survival of a broad spectrum of human tumors [42]. | Yes [42] | Yes [43] |
4zzxA | Poly [ADP-ribose] polymerase 2 | −59.83 | Involved in a number of cellular processes such as DNA repair, genomic stability, programmed cell death [44]. | Yes [45] | Yes [46,47] |
2ffqA | Ras-related protein Rab-6B | −59.78 | Protein has a regulatory role in the retrograde transport of cargo in neutral cells [48,49]. | Yes [49] | No |
4lhwA | Ras-related protein Rab-8A | −59.77 | Overactivity of Ras signaling can lead to cancer, and it was found in human tumors [49]. | No | No |
3ru0A | SET and MYND domain-containing protein 3 | −59.53 | Regulates chromatin during the development of myocardial and skeletal muscles [50]. | Yes [50] | No |
3ma2D | Matrix metalloproteinase-14 | −59.24 | Plays a critical role in conferring cells with the ability to remodel and penetrate the extracellular matrix [51]. | Yes [51] | No |
3lawA | Ras-related protein Rab-7a | −58.93 | Ras inhibitors have been studied as a treatment for cancer and other diseases with Ras overexpression [49]. | No | No |
1zd9A | ADP-ribosylation factor-like 10B | −57.56 | Physiological function of this protein is not known. | No | No |
1vzoA | Ribosomal protein S6 kinase alpha 5 | −57.32 | Involved in several pathways such as MAPK signaling pathway, adrenergic signaling in cardiomyocytes, TNF signaling pathway, and possesses several biochemical functions such as ATP binding, histone kinase activity (H3-S10 specific), magnesium ion binding [52]. | Yes [52] | No |
5fbeA | Complement factor D | −57.27 | The complement system plays an important role in the innate defense against common invading pathogens [53]. | No | No |
1mrqA | Aldo-keto reductase family 1 member C1 | −56.90 | Involved in maintaining steroid hormone homeostasis, prostaglandin metabolism, and metabolic activation of polycyclic aromatic hydrocarbons [54]. | Yes [54] | No |
2c73A | Amine oxidase (flavin-containing) B | −56.87 | Plays an important role in neuroactive, vasoactive amines and is correlated with the production of neurotoxins in Parkinson’s disease [55]. | No | No |
1zq9A | Probable dimethyladenosine transferase | −56.86 | Protein is involved in the pre-rRNA procedure, which leads to small-subunit rRNA production [56]. | Yes [56] | No |
5fa6A | NADPH- -cytochrome P450 reductase | −56.81 | Protein is the redox partner of various P450s involved in primary and secondary metabolism [57]. | No | No |
2h44A | cGMP-specific 3′,5′-cyclic phosphodiesterase | −56.65 | The protein catalyzes the hydrolysis of 3′,5′-cyclic nucleotides to their respective nucleoside 5′-monophosphates [58]. | No | No |
1ck7A | Gelatinase A | −56.53 | Protein is a member of the gelatin-binding structure group and forms part of the matrix metalloproteinases (MMPs) [59]. | Yes [59] | Yes [60] |
1t91A | Ras-related protein Rab-7 | −56.21 | Ras signaling proteins have been found in human tumors [49]. | No | No |
3ghvA | Dihydrofolate reductase | −56.01 | Converts dihydrofolate into tetrahydrofolate and plays a crucial role in cell metabolism and cellular growth [61]. | Yes [62] | No |
3gz9A | Peroxisome proliferator-activated receptor delta | −55.95 | Protein is involved in differentiation, lipid accumulation, directional sensing, polarization, and migration of keratinocytes [63,64]. | Yes [64] | No |
2bzgA | Thiopurine S-methyltransferase | −55.80 | Protein is an enzyme in the cytoplasm that is involved in catalyzing the S-methylation of thiopurine drugs [65]. | No | No |
1zc3A | Ras-related protein Ral-A | −55.56 | Because of presence of Ras proteins in tumor, the Ras inhibitors have been studied [49]. | No | No |
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Kores, K.; Kolenc, Z.; Furlan, V.; Bren, U. Inverse Molecular Docking Elucidating the Anticarcinogenic Potential of the Hop Natural Product Xanthohumol and Its Metabolites. Foods 2022, 11, 1253. https://doi.org/10.3390/foods11091253
Kores K, Kolenc Z, Furlan V, Bren U. Inverse Molecular Docking Elucidating the Anticarcinogenic Potential of the Hop Natural Product Xanthohumol and Its Metabolites. Foods. 2022; 11(9):1253. https://doi.org/10.3390/foods11091253
Chicago/Turabian StyleKores, Katarina, Zala Kolenc, Veronika Furlan, and Urban Bren. 2022. "Inverse Molecular Docking Elucidating the Anticarcinogenic Potential of the Hop Natural Product Xanthohumol and Its Metabolites" Foods 11, no. 9: 1253. https://doi.org/10.3390/foods11091253