In silico directed evolution of Anabas testudineus AtMP1 antimicrobial peptide to improve in vitro anticancer activity
Various studies have demonstrated that directed evolution is a powerful tool in enhancing protein properties. In this study, directed evolution was used to enhance the efficacy of synthesised Anabas testudineus AtMP1 antimicrobial peptides (AMPs) in inhibiting the proliferation of cancer cells. The...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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PeerJ
2024
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| Online Access: | http://psasir.upm.edu.my/id/eprint/116710/ http://psasir.upm.edu.my/id/eprint/116710/1/116710.pdf |
| _version_ | 1848867072520486912 |
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| author | Fazry, Shazrul Najm, Ahmed Abdulkareem Mahdi, Ibrahim Mahmood Ang, Arnold Lee, LiTing Loh, Choy-Theng Syed Alwi, Sharifah Sakinah Li, Fang Law, Douglas |
| author_facet | Fazry, Shazrul Najm, Ahmed Abdulkareem Mahdi, Ibrahim Mahmood Ang, Arnold Lee, LiTing Loh, Choy-Theng Syed Alwi, Sharifah Sakinah Li, Fang Law, Douglas |
| author_sort | Fazry, Shazrul |
| building | UPM Institutional Repository |
| collection | Online Access |
| description | Various studies have demonstrated that directed evolution is a powerful tool in enhancing protein properties. In this study, directed evolution was used to enhance the efficacy of synthesised Anabas testudineus AtMP1 antimicrobial peptides (AMPs) in inhibiting the proliferation of cancer cells. The modification of antimicrobial peptides (AMPs) and prediction of peptide properties using bioinformatic tools were carried out using four databases, including ADP3, CAMP-R3, AMPfun, and ANTICP. One modified antimicrobial peptide (AMP), ATMP6 (THPPTTTTTTTTTTTTTAAPARTT), was chosen based on its projected potent anticancer effect, taking into account factors such as amino acid length, net charge, anticancer activity score, and hydrophobicity. The selected AMPs were subjected to study in deep-learning databases, namely ToxIBTL and ToxinPred2, to predict their toxicity. Furthermore, the allergic properties of these antimicrobial peptides (AMPs) were verified by utilising AllerTOP and AllergenFP. Based on the results obtained from the database study, it was projected that antimicrobial peptides (AMPs) demonstrate a lack of toxicity towards human cells that is indicative of the broader population. After 48 hours of incubation, the IC50 values of ATMP6 against the HS27 and MDA-MB-231 cell lines were found to be 48.03 ± 0.013 µg/ml and 7.52 ± 0.027 µg/ml, respectively. The IC50 values of the original peptide ATMP1 against the MDA-MB-231 and HS27 cell lines were determined to be 59.6 ± 0.14 µg/ml and 8.25 ± 0.14 µg/ml, respectively, when compared. Furthermore, the results indicated that the injection of ATMP6 induced apoptosis in the MDA-MB-231 cell lines. The present investigation has revealed new opportunities for advancing novel targeted peptide therapeutics to tackle cancer. |
| first_indexed | 2025-11-15T14:30:41Z |
| format | Article |
| id | upm-116710 |
| institution | Universiti Putra Malaysia |
| institution_category | Local University |
| language | English |
| last_indexed | 2025-11-15T14:30:41Z |
| publishDate | 2024 |
| publisher | PeerJ |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | upm-1167102025-04-15T02:52:21Z http://psasir.upm.edu.my/id/eprint/116710/ In silico directed evolution of Anabas testudineus AtMP1 antimicrobial peptide to improve in vitro anticancer activity Fazry, Shazrul Najm, Ahmed Abdulkareem Mahdi, Ibrahim Mahmood Ang, Arnold Lee, LiTing Loh, Choy-Theng Syed Alwi, Sharifah Sakinah Li, Fang Law, Douglas Various studies have demonstrated that directed evolution is a powerful tool in enhancing protein properties. In this study, directed evolution was used to enhance the efficacy of synthesised Anabas testudineus AtMP1 antimicrobial peptides (AMPs) in inhibiting the proliferation of cancer cells. The modification of antimicrobial peptides (AMPs) and prediction of peptide properties using bioinformatic tools were carried out using four databases, including ADP3, CAMP-R3, AMPfun, and ANTICP. One modified antimicrobial peptide (AMP), ATMP6 (THPPTTTTTTTTTTTTTAAPARTT), was chosen based on its projected potent anticancer effect, taking into account factors such as amino acid length, net charge, anticancer activity score, and hydrophobicity. The selected AMPs were subjected to study in deep-learning databases, namely ToxIBTL and ToxinPred2, to predict their toxicity. Furthermore, the allergic properties of these antimicrobial peptides (AMPs) were verified by utilising AllerTOP and AllergenFP. Based on the results obtained from the database study, it was projected that antimicrobial peptides (AMPs) demonstrate a lack of toxicity towards human cells that is indicative of the broader population. After 48 hours of incubation, the IC50 values of ATMP6 against the HS27 and MDA-MB-231 cell lines were found to be 48.03 ± 0.013 µg/ml and 7.52 ± 0.027 µg/ml, respectively. The IC50 values of the original peptide ATMP1 against the MDA-MB-231 and HS27 cell lines were determined to be 59.6 ± 0.14 µg/ml and 8.25 ± 0.14 µg/ml, respectively, when compared. Furthermore, the results indicated that the injection of ATMP6 induced apoptosis in the MDA-MB-231 cell lines. The present investigation has revealed new opportunities for advancing novel targeted peptide therapeutics to tackle cancer. PeerJ 2024-09-26 Article PeerReviewed text en cc_by_4 http://psasir.upm.edu.my/id/eprint/116710/1/116710.pdf Fazry, Shazrul and Najm, Ahmed Abdulkareem and Mahdi, Ibrahim Mahmood and Ang, Arnold and Lee, LiTing and Loh, Choy-Theng and Syed Alwi, Sharifah Sakinah and Li, Fang and Law, Douglas (2024) In silico directed evolution of Anabas testudineus AtMP1 antimicrobial peptide to improve in vitro anticancer activity. PeerJ, 12 (9). art. no. e17894. ISSN 2167-8359; eISSN: 2167-8359 https://peerj.com/articles/17894/ 10.7717/peerj.17894 |
| spellingShingle | Fazry, Shazrul Najm, Ahmed Abdulkareem Mahdi, Ibrahim Mahmood Ang, Arnold Lee, LiTing Loh, Choy-Theng Syed Alwi, Sharifah Sakinah Li, Fang Law, Douglas In silico directed evolution of Anabas testudineus AtMP1 antimicrobial peptide to improve in vitro anticancer activity |
| title | In silico directed evolution of Anabas testudineus AtMP1 antimicrobial peptide to improve in vitro anticancer activity |
| title_full | In silico directed evolution of Anabas testudineus AtMP1 antimicrobial peptide to improve in vitro anticancer activity |
| title_fullStr | In silico directed evolution of Anabas testudineus AtMP1 antimicrobial peptide to improve in vitro anticancer activity |
| title_full_unstemmed | In silico directed evolution of Anabas testudineus AtMP1 antimicrobial peptide to improve in vitro anticancer activity |
| title_short | In silico directed evolution of Anabas testudineus AtMP1 antimicrobial peptide to improve in vitro anticancer activity |
| title_sort | in silico directed evolution of anabas testudineus atmp1 antimicrobial peptide to improve in vitro anticancer activity |
| url | http://psasir.upm.edu.my/id/eprint/116710/ http://psasir.upm.edu.my/id/eprint/116710/ http://psasir.upm.edu.my/id/eprint/116710/ http://psasir.upm.edu.my/id/eprint/116710/1/116710.pdf |