Cargando…

A Molecular Docking Study of Human STEAP2 for the Discovery of New Potential Anti-Prostate Cancer Chemotherapeutic Candidates

Prostate cancer is a rising health concern and accounts for 3.8% of all cancer deaths globally. Uganda has one of the highest incidence rates of the disease in Africa at 5.2% with the majority of diagnosed patients found to have advanced disease. This study aimed to use the STEAP2 protein (prostate...

Descripción completa

Detalles Bibliográficos
Autores principales: Ongaba, Timothy, Ndekezi, Christian, Nakiddu, Nana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9580961/
https://www.ncbi.nlm.nih.gov/pubmed/36304279
http://dx.doi.org/10.3389/fbinf.2022.869375
_version_ 1784812509999398912
author Ongaba, Timothy
Ndekezi, Christian
Nakiddu, Nana
author_facet Ongaba, Timothy
Ndekezi, Christian
Nakiddu, Nana
author_sort Ongaba, Timothy
collection PubMed
description Prostate cancer is a rising health concern and accounts for 3.8% of all cancer deaths globally. Uganda has one of the highest incidence rates of the disease in Africa at 5.2% with the majority of diagnosed patients found to have advanced disease. This study aimed to use the STEAP2 protein (prostate cancer–specific biomarker) for the discovery of new targeted therapy. To determine the most likely compound that can bind to the STEAP2 protein, we docked the modeled STEAP2 3D structure against 2466 FDA (Food and Drug Administration)-approved drug candidates using AutoDock Vina. Protein basic local alignment search tool (BLASTp) search, multiple sequence alignment (MSA), and phylogenetics were further carried out to analyze the diversity of this marker and determine its conserved domains as suitable target regions. Six promising drug candidates (ligands) were identified. Triptorelin had the highest binding energy (−12.1 kcal/mol) followed by leuprolide (docking energy: −11.2 kcal/mol). All the top two drug candidates interacted with residues Ser-372 and Gly-369 in close proximity with the iron-binding domain (an important catalyst of metal reduction). The two drugs had earlier been approved for the treatment of advanced prostate cancer with an elusive mode of action. Through this study, further insight into figuring out their interaction with STEAP2 might be important during treatment.
format Online
Article
Text
id pubmed-9580961
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-95809612022-10-26 A Molecular Docking Study of Human STEAP2 for the Discovery of New Potential Anti-Prostate Cancer Chemotherapeutic Candidates Ongaba, Timothy Ndekezi, Christian Nakiddu, Nana Front Bioinform Bioinformatics Prostate cancer is a rising health concern and accounts for 3.8% of all cancer deaths globally. Uganda has one of the highest incidence rates of the disease in Africa at 5.2% with the majority of diagnosed patients found to have advanced disease. This study aimed to use the STEAP2 protein (prostate cancer–specific biomarker) for the discovery of new targeted therapy. To determine the most likely compound that can bind to the STEAP2 protein, we docked the modeled STEAP2 3D structure against 2466 FDA (Food and Drug Administration)-approved drug candidates using AutoDock Vina. Protein basic local alignment search tool (BLASTp) search, multiple sequence alignment (MSA), and phylogenetics were further carried out to analyze the diversity of this marker and determine its conserved domains as suitable target regions. Six promising drug candidates (ligands) were identified. Triptorelin had the highest binding energy (−12.1 kcal/mol) followed by leuprolide (docking energy: −11.2 kcal/mol). All the top two drug candidates interacted with residues Ser-372 and Gly-369 in close proximity with the iron-binding domain (an important catalyst of metal reduction). The two drugs had earlier been approved for the treatment of advanced prostate cancer with an elusive mode of action. Through this study, further insight into figuring out their interaction with STEAP2 might be important during treatment. Frontiers Media S.A. 2022-05-24 /pmc/articles/PMC9580961/ /pubmed/36304279 http://dx.doi.org/10.3389/fbinf.2022.869375 Text en Copyright © 2022 Ongaba, Ndekezi and Nakiddu. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Bioinformatics
Ongaba, Timothy
Ndekezi, Christian
Nakiddu, Nana
A Molecular Docking Study of Human STEAP2 for the Discovery of New Potential Anti-Prostate Cancer Chemotherapeutic Candidates
title A Molecular Docking Study of Human STEAP2 for the Discovery of New Potential Anti-Prostate Cancer Chemotherapeutic Candidates
title_full A Molecular Docking Study of Human STEAP2 for the Discovery of New Potential Anti-Prostate Cancer Chemotherapeutic Candidates
title_fullStr A Molecular Docking Study of Human STEAP2 for the Discovery of New Potential Anti-Prostate Cancer Chemotherapeutic Candidates
title_full_unstemmed A Molecular Docking Study of Human STEAP2 for the Discovery of New Potential Anti-Prostate Cancer Chemotherapeutic Candidates
title_short A Molecular Docking Study of Human STEAP2 for the Discovery of New Potential Anti-Prostate Cancer Chemotherapeutic Candidates
title_sort molecular docking study of human steap2 for the discovery of new potential anti-prostate cancer chemotherapeutic candidates
topic Bioinformatics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9580961/
https://www.ncbi.nlm.nih.gov/pubmed/36304279
http://dx.doi.org/10.3389/fbinf.2022.869375
work_keys_str_mv AT ongabatimothy amoleculardockingstudyofhumansteap2forthediscoveryofnewpotentialantiprostatecancerchemotherapeuticcandidates
AT ndekezichristian amoleculardockingstudyofhumansteap2forthediscoveryofnewpotentialantiprostatecancerchemotherapeuticcandidates
AT nakiddunana amoleculardockingstudyofhumansteap2forthediscoveryofnewpotentialantiprostatecancerchemotherapeuticcandidates
AT ongabatimothy moleculardockingstudyofhumansteap2forthediscoveryofnewpotentialantiprostatecancerchemotherapeuticcandidates
AT ndekezichristian moleculardockingstudyofhumansteap2forthediscoveryofnewpotentialantiprostatecancerchemotherapeuticcandidates
AT nakiddunana moleculardockingstudyofhumansteap2forthediscoveryofnewpotentialantiprostatecancerchemotherapeuticcandidates