Cargando…

In Silico Investigation of a Chimeric IL24-LK6 Fusion Protein as a Potent Candidate Against Breast Cancer

Targeted delivery of therapeutic anticancer chimeric molecules enhances the efficacy of drug by improving cellular uptake and circulation time. Engineering the molecules to facilitate the specific interaction between chimeric protein and its receptor is critical to elucidate biological mechanism as...

Descripción completa

Detalles Bibliográficos
Autores principales: Muhammad Rehman, Hafiz, Rehman, Hafiz Muzzammel, Naveed, Muhammad, Khan, Muhammad Tahir, Shabbir, Muhammad Aqib, Aslam, Shakira, Bashir, Hamid
Formato: Online Artículo Texto
Lenguaje:English
Publicado: SAGE Publications 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10291407/
https://www.ncbi.nlm.nih.gov/pubmed/37377793
http://dx.doi.org/10.1177/11779322231182560
_version_ 1785062689221902336
author Muhammad Rehman, Hafiz
Rehman, Hafiz Muzzammel
Naveed, Muhammad
Khan, Muhammad Tahir
Shabbir, Muhammad Aqib
Aslam, Shakira
Bashir, Hamid
author_facet Muhammad Rehman, Hafiz
Rehman, Hafiz Muzzammel
Naveed, Muhammad
Khan, Muhammad Tahir
Shabbir, Muhammad Aqib
Aslam, Shakira
Bashir, Hamid
author_sort Muhammad Rehman, Hafiz
collection PubMed
description Targeted delivery of therapeutic anticancer chimeric molecules enhances the efficacy of drug by improving cellular uptake and circulation time. Engineering the molecules to facilitate the specific interaction between chimeric protein and its receptor is critical to elucidate biological mechanism as well as accuracy in modeling of complexes. A theoretically designed novel protein-protein interfaces can serve as a bottom-up method for comprehensive understanding of interacting protein residues. This study was aimed for in silico analyses of a chimeric fusion protein against breast cancer. The amino acid sequences of the interleukin 24 (IL-24) and LK-6 peptide were used to design the chimeric fusion protein via a rigid linker. The secondary and tertiary structures along with physicochemical properties by ProtParam and solubility were predicted using online software. The validation and quality of the fusion protein was confirmed by Rampage and ERRAT2. The newly designed fusion construct has a total length of 179 amino acids. The top-ranked structure from alpha fold2 showed 18.1 KD molecular weight by ProtParam, quality factor of 94.152 by ERRAT, and a valid structure by a Ramachandran plot with 88.5% residues in the favored region. Finally, the docking and simulation studies were performed using HADDOCK and Desmond module of Schrodinger. The quality, validity, interaction analysis, and stability of the fusion protein depict a functional molecule. The fusion gene IL24-LK6 after cloning and expression in a suitable prokaryotic cell might be a useful candidate for developing a novel anticancer therapy.
format Online
Article
Text
id pubmed-10291407
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher SAGE Publications
record_format MEDLINE/PubMed
spelling pubmed-102914072023-06-27 In Silico Investigation of a Chimeric IL24-LK6 Fusion Protein as a Potent Candidate Against Breast Cancer Muhammad Rehman, Hafiz Rehman, Hafiz Muzzammel Naveed, Muhammad Khan, Muhammad Tahir Shabbir, Muhammad Aqib Aslam, Shakira Bashir, Hamid Bioinform Biol Insights Original Research Article Targeted delivery of therapeutic anticancer chimeric molecules enhances the efficacy of drug by improving cellular uptake and circulation time. Engineering the molecules to facilitate the specific interaction between chimeric protein and its receptor is critical to elucidate biological mechanism as well as accuracy in modeling of complexes. A theoretically designed novel protein-protein interfaces can serve as a bottom-up method for comprehensive understanding of interacting protein residues. This study was aimed for in silico analyses of a chimeric fusion protein against breast cancer. The amino acid sequences of the interleukin 24 (IL-24) and LK-6 peptide were used to design the chimeric fusion protein via a rigid linker. The secondary and tertiary structures along with physicochemical properties by ProtParam and solubility were predicted using online software. The validation and quality of the fusion protein was confirmed by Rampage and ERRAT2. The newly designed fusion construct has a total length of 179 amino acids. The top-ranked structure from alpha fold2 showed 18.1 KD molecular weight by ProtParam, quality factor of 94.152 by ERRAT, and a valid structure by a Ramachandran plot with 88.5% residues in the favored region. Finally, the docking and simulation studies were performed using HADDOCK and Desmond module of Schrodinger. The quality, validity, interaction analysis, and stability of the fusion protein depict a functional molecule. The fusion gene IL24-LK6 after cloning and expression in a suitable prokaryotic cell might be a useful candidate for developing a novel anticancer therapy. SAGE Publications 2023-06-23 /pmc/articles/PMC10291407/ /pubmed/37377793 http://dx.doi.org/10.1177/11779322231182560 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by-nc/4.0/This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page(https://us.sagepub.com/en-us/nam/open-access-at-sage).
spellingShingle Original Research Article
Muhammad Rehman, Hafiz
Rehman, Hafiz Muzzammel
Naveed, Muhammad
Khan, Muhammad Tahir
Shabbir, Muhammad Aqib
Aslam, Shakira
Bashir, Hamid
In Silico Investigation of a Chimeric IL24-LK6 Fusion Protein as a Potent Candidate Against Breast Cancer
title In Silico Investigation of a Chimeric IL24-LK6 Fusion Protein as a Potent Candidate Against Breast Cancer
title_full In Silico Investigation of a Chimeric IL24-LK6 Fusion Protein as a Potent Candidate Against Breast Cancer
title_fullStr In Silico Investigation of a Chimeric IL24-LK6 Fusion Protein as a Potent Candidate Against Breast Cancer
title_full_unstemmed In Silico Investigation of a Chimeric IL24-LK6 Fusion Protein as a Potent Candidate Against Breast Cancer
title_short In Silico Investigation of a Chimeric IL24-LK6 Fusion Protein as a Potent Candidate Against Breast Cancer
title_sort in silico investigation of a chimeric il24-lk6 fusion protein as a potent candidate against breast cancer
topic Original Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10291407/
https://www.ncbi.nlm.nih.gov/pubmed/37377793
http://dx.doi.org/10.1177/11779322231182560
work_keys_str_mv AT muhammadrehmanhafiz insilicoinvestigationofachimericil24lk6fusionproteinasapotentcandidateagainstbreastcancer
AT rehmanhafizmuzzammel insilicoinvestigationofachimericil24lk6fusionproteinasapotentcandidateagainstbreastcancer
AT naveedmuhammad insilicoinvestigationofachimericil24lk6fusionproteinasapotentcandidateagainstbreastcancer
AT khanmuhammadtahir insilicoinvestigationofachimericil24lk6fusionproteinasapotentcandidateagainstbreastcancer
AT shabbirmuhammadaqib insilicoinvestigationofachimericil24lk6fusionproteinasapotentcandidateagainstbreastcancer
AT aslamshakira insilicoinvestigationofachimericil24lk6fusionproteinasapotentcandidateagainstbreastcancer
AT bashirhamid insilicoinvestigationofachimericil24lk6fusionproteinasapotentcandidateagainstbreastcancer