Computational Modeling on Aquaporin-3 as Skin Cancer Target: A Virtual Screening Study.
AQP3 protein
MM-GBSA analysis
molecular docking
molecular dynamics
pharmacophore-based filter
Journal
Frontiers in chemistry
ISSN: 2296-2646
Titre abrégé: Front Chem
Pays: Switzerland
ID NLM: 101627988
Informations de publication
Date de publication:
2020
2020
Historique:
received:
18
12
2019
accepted:
17
03
2020
entrez:
1
5
2020
pubmed:
1
5
2020
medline:
1
5
2020
Statut:
epublish
Résumé
Aquaporin-3 (AQP3) is one of the aquaglyceroporins, which is expressed in the basolateral layer of the skin membrane. Studies have reported that human skin squamous cell carcinoma overexpresses AQP3 and inhibition of its function may alleviate skin tumorigenesis. In the present study, we have applied a virtual screening method that encompasses filters for physicochemical properties and molecular docking to select potential hit compounds that bind to the Aquaporin-3 protein. Based on molecular docking results, the top 20 hit compounds were analyzed for stability in the binding pocket using unconstrained molecular dynamics simulations and further evaluated for binding free energy. Furthermore, examined the ligand-unbinding pathway of the inhibitor from its bound form to explore possible routes for inhibitor approach to the ligand-binding site. With a good docking score, stability in the binding pocket, and free energy of binding, these hit compounds can be developed as Aquaporin-3 inhibitors in the near future.
Identifiants
pubmed: 32351935
doi: 10.3389/fchem.2020.00250
pmc: PMC7175779
doi:
Types de publication
Journal Article
Langues
eng
Pagination
250Informations de copyright
Copyright © 2020 Yadav, Kumar, Choi, Chaudhary and Kim.
Références
Chem Commun (Camb). 2017 Mar 30;53(27):3830-3833
pubmed: 28304043
J Cell Physiol. 2014 Nov;229(11):1787-801
pubmed: 24676973
Chemistry. 2019 Jul 2;25(37):8713-8718
pubmed: 31081563
Prog Histochem Cytochem. 2004;39(1):1-83
pubmed: 15242101
Proteins. 2011 Oct;79(10):2794-812
pubmed: 21905107
J Pharm Sci. 2008 Jan;97(1):584-98
pubmed: 17722002
FEBS Lett. 2002 Nov 20;531(3):443-7
pubmed: 12435590
J Mol Model. 2012 Jun;18(6):2513-25
pubmed: 22038459
Front Pharmacol. 2018 Jun 27;9:644
pubmed: 29997501
CA Cancer J Clin. 2003 Jan-Feb;53(1):5-26
pubmed: 12568441
J Biol Chem. 1993 Jan 5;268(1):17-20
pubmed: 7677994
J Chem Inf Model. 2009 Feb;49(2):377-89
pubmed: 19434839
J Chem Theory Comput. 2011 Dec 13;7(12):4026-37
pubmed: 26598349
Adv Drug Deliv Rev. 2006 Nov 30;58(12-13):1431-50
pubmed: 17097188
J Cell Biochem. 2020 Jan 6;:
pubmed: 31904142
J Biomol Struct Dyn. 2020 Mar 2;:1-11
pubmed: 32072876
Proc Natl Acad Sci U S A. 2010 Oct 5;107(40):17164-9
pubmed: 20855585
J Chem Inf Model. 2013 Jan 28;53(1):201-9
pubmed: 23268595
Phys Rev E Stat Phys Plasmas Fluids Relat Interdiscip Topics. 1993 May;47(5):3145-3151
pubmed: 9960366
Sci Rep. 2016 Dec 06;6:38128
pubmed: 27922047
J Comput Aided Mol Des. 2013 Mar;27(3):221-34
pubmed: 23579614
Curr Drug Targets. 2014;15(8):753-61
pubmed: 24975562
Proc Natl Acad Sci U S A. 2003 Jun 10;100(12):7360-5
pubmed: 12771381
Cell Commun Signal. 2015 Sep 14;13:39
pubmed: 26369938
J Med Chem. 2004 Mar 25;47(7):1739-49
pubmed: 15027865
Pharm Res. 1995 Nov;12(11):1628-33
pubmed: 8592661
J Comput Chem. 2018 Apr 30;39(11):665-678
pubmed: 29315658
J Membr Biol. 1996 Oct;153(3):171-80
pubmed: 8849412
Int J Pharm. 2011 Oct 10;418(1):115-29
pubmed: 21356301
Drug Des Devel Ther. 2017 Jun 22;11:1859-1870
pubmed: 28694686
PLoS One. 2012;7(5):e37435
pubmed: 22624030
Br J Dermatol. 2003 Dec;149(6):1200-6
pubmed: 14674897
Crit Rev Oncol Hematol. 2002 Mar;41(3):269-85
pubmed: 11880204
ChemMedChem. 2013 Jul;8(7):1086-92
pubmed: 23653381
Nat Rev Drug Discov. 2014 Apr;13(4):259-77
pubmed: 24625825
J Chem Inf Model. 2011 Apr 25;51(4):777-87
pubmed: 21417262
Drug Des Devel Ther. 2010 Sep 07;4:173-86
pubmed: 20856844
J Mol Med (Berl). 2008 May;86(5):523-9
pubmed: 18311471
J Chem Theory Comput. 2010 May 11;6(5):1509-19
pubmed: 26615687
Med Chem. 2013 Dec;9(8):1073-84
pubmed: 23675978
Mol Pharmacol. 2009 Jul;76(1):105-12
pubmed: 19403703
Acta Pharmacol Sin. 2004 Jan;25(1):90-7
pubmed: 14704128
J Invest Dermatol. 2012 Sep;132(9):2131-3
pubmed: 22895445
Curr Opin Struct Biol. 2002 Aug;12(4):509-15
pubmed: 12163075
Annu Rev Med. 2012;63:303-16
pubmed: 22248325
J Invest Dermatol. 2008 Sep;128(9):2145-51
pubmed: 18548108
Mol Cell Biol. 2008 Jan;28(1):326-32
pubmed: 17967887
J Comput Aided Mol Des. 2009 Aug;23(8):541-54
pubmed: 19421721
J Am Soc Nephrol. 2013 Apr;24(5):685-6
pubmed: 23599384
Pharm Res. 1992 May;9(5):663-9
pubmed: 1608900
Biochim Biophys Acta. 2001 Dec 3;1522(2):82-8
pubmed: 11750058
J Mol Med (Berl). 2008 Feb;86(2):221-31
pubmed: 17968524
Sci Rep. 2018 Mar 19;8(1):4777
pubmed: 29556059
Arch Pharm Res. 2018 Dec;41(12):1178-1189
pubmed: 28822076
J Cheminform. 2009 May 20;1(1):6
pubmed: 20298524
Chem Biol Drug Des. 2006 May;67(5):370-2
pubmed: 16784462
Metallomics. 2018 May 23;10(5):696-712
pubmed: 29766198
J Comput Chem. 2004 Oct;25(13):1656-76
pubmed: 15264259
Int J Cancer. 1985 Apr 15;35(4):427-33
pubmed: 3988369
Inorg Chem. 2019 Feb 4;58(3):2140-2148
pubmed: 30645101
Am J Physiol Renal Physiol. 2000 Jan;278(1):F13-28
pubmed: 10644652
Sci Rep. 2015 Jul 29;5:12484
pubmed: 26219409
Mol Pharmacol. 2016 Jan;89(1):133-40
pubmed: 26467039
J Drug Target. 1998;6(2):151-65
pubmed: 9886238
J Biomol Struct Dyn. 2020 Mar 5;:1-11
pubmed: 32072880
J Biol Chem. 2002 Nov 29;277(48):46616-21
pubmed: 12270942
Curr Med Chem. 2014;21(9):1160-70
pubmed: 24180274
J Chem Inf Model. 2017 May 22;57(5):1013-1017
pubmed: 28459556
Sci Rep. 2019 Mar 14;9(1):4496
pubmed: 30872693
Int J Mol Sci. 2017 Oct 07;18(10):
pubmed: 28991174
Mol Pharmacol. 2000 May;57(5):1021-6
pubmed: 10779387
ACS Chem Biol. 2011 Mar 18;6(3):208-17
pubmed: 21261294
Sci Rep. 2020 Feb 25;10(1):3396
pubmed: 32099012