Computational Screening for the Anticancer Potential of Seed-Derived Antioxidant Peptides: A Cheminformatic Approach

Abstract

Some seed-derived antioxidant peptides are known to regulate cellular modulators of ROS production, including those proposed to be promising targets of anticancer therapy. Nevertheless, research in this direction is relatively slow owing to the inevitable time-consuming nature of wet-lab experimentations. To help expedite such explorations, we performed structure-based virtual screening on seed-derived antioxidant peptides in the literature for anticancer potential. The ability of the peptides to interact with myeloperoxidase, xanthine oxidase, Keap1, and p47phox was examined. We generated a virtual library of 677 peptides based on a database and literature search. Screening for anticancer potential, non-toxicity, non-allergenicity, non-hemolyticity narrowed down the collection to five candidates. Molecular docking found LYSPH as the most promising in targeting myeloperoxidase, xanthine oxidase, and Keap1, whereas PSYLNTPLL was the best candidate to bind stably to key residues in p47phox. Stability of the four peptide-target complexes was supported by molecular dynamics simulation. LYSPH and PSYLNTPLL were predicted to have cell- and blood-brain barrier penetrating potential, although intolerant to gastrointestinal digestion. Computational alanine scanning found tyrosine residues in both peptides as crucial to stable binding to the targets. Overall, LYSPH and PSYLNTPLL are two potential anticancer peptides that deserve deeper exploration in future.

Open-Source Browser-Based Tools for Structure-Based Computer-Aided Drug Discovery

“…Webina thus simplifies the docking process, making it accessible even to novices. Though only recently published, several researchers have already used Webina to study compounds with analgesic [ 62 ], anti-cancer [ 63 , 64 ], anti-bacterial [ 65 ], anti-viral [ 66 , 67 , 68 ], and antioxidant [ 69 ] properties, among others [ 70 , 71 ]. The Webina app and source code are freely available online under the terms of the open-source Apache License, version 2.0 ( Table 1 ).…”

Bioactive peptides derived fromRadix Angelicae sinensisinhibit ferroptosis in HT22 cells through direct Keap1–Nrf2 PPI inhibition

“…Notably, bioactive peptides originated from plant proteins have captured worldwide attention due to their advantages of environmental protection, sustainability, low cost, and low toxicity. [12][13][14][15] So far, a large number of Keap1-Nrf2 PPI inhibitory peptides have been isolated from plant proteins. For instance, peptides from Acaudina molpadioides, cottonseed, and broken rice, exert great antioxidant activity in vitro and in vivo through Keap1-Nrf2 PPI inhibition.…”

Redox Active Molecules in Cancer Treatments

“…They present antioxidative or targeted oxidative effects of miscellaneous small-molecular-weight compounds or proteins against a variety of cancer types: An endogenous compound—melatonin [ 2 ]. Natural plant compounds (naringenin [ 3 ], papaverine [ 4 ], polyphenols isolated from Myrciaria trunciflora [ 5 ] or Anneslea fragrans [ 6 ], and seed-derived peptides [ 7 ]), natural compounds also found in animals (melatonin [ 2 , 8 ]), and peptides as well as proteins from Jellyfish venom [ 9 ]. Synthetic compounds, i.e., alkyl thiols [ 10 ], dimethyl sulfoxide [ 11 ], metformin and S63845 [ 12 ], the ruthenium complex [Ru(Phen) 3 ] 2+ [ 13 ], and copper-based compounds—Casiopeinas [ 14 ].…”

“…Natural plant compounds (naringenin [ 3 ], papaverine [ 4 ], polyphenols isolated from Myrciaria trunciflora [ 5 ] or Anneslea fragrans [ 6 ], and seed-derived peptides [ 7 ]), natural compounds also found in animals (melatonin [ 2 , 8 ]), and peptides as well as proteins from Jellyfish venom [ 9 ].…”

“…Some other studies used in vitro assays such as cell cycle analyses [ 2 , 3 , 4 , 9 ], DNA fragmentation assays [ 3 , 9 ], analyses of the expression of apoptosis-related proteins and/or genes [ 9 , 11 , 12 ], etc. The two included studies are based on the application of state-of-the-art chemoinformatic analysis and modeling approaches—molecular docking and molecular dynamics [ 7 , 18 ].…”