The role of SAXS and molecular simulations in 3D structure elucidation of a DNA aptamer against lung cancer.
SAXS
aptamer
fragment molecular orbital
lung adenocarcinoma
molecular dynamics
molecular simulations
oligonucleotide
small-angle X-ray scattering
spatial structure
tertiary structure
Journal
Molecular therapy. Nucleic acids
ISSN: 2162-2531
Titre abrégé: Mol Ther Nucleic Acids
Pays: United States
ID NLM: 101581621
Informations de publication
Date de publication:
03 Sep 2021
03 Sep 2021
Historique:
received:
22
01
2021
accepted:
17
07
2021
entrez:
30
8
2021
pubmed:
31
8
2021
medline:
31
8
2021
Statut:
epublish
Résumé
Aptamers are short, single-stranded DNA or RNA oligonucleotide molecules that function as synthetic analogs of antibodies and bind to a target molecule with high specificity. Aptamer affinity entirely depends on its tertiary structure and charge distribution. Therefore, length and structure optimization are essential for increasing aptamer specificity and affinity. Here, we present a general optimization procedure for finding the most populated atomistic structures of DNA aptamers. Based on the existed aptamer LC-18 for lung adenocarcinoma, a new truncated LC-18 (LC-18t) aptamer LC-18t was developed. A three-dimensional (3D) shape of LC-18t was reported based on small-angle X-ray scattering (SAXS) experiments and molecular modeling by fragment molecular orbital or molecular dynamic methods. Molecular simulations revealed an ensemble of possible aptamer conformations in solution that were in close agreement with measured SAXS data. The aptamer LC-18t had stronger binding to cancerous cells in lung tumor tissues and shared the binding site with the original larger aptamer. The suggested approach reveals 3D shapes of aptamers and helps in designing better affinity probes.
Identifiants
pubmed: 34458013
doi: 10.1016/j.omtn.2021.07.015
pii: S2162-2531(21)00183-9
pmc: PMC8379633
doi:
Types de publication
Journal Article
Langues
eng
Pagination
316-327Informations de copyright
© 2021.
Déclaration de conflit d'intérêts
The authors declare no competing interests.
Références
J Am Chem Soc. 2006 Jun 21;128(24):7929-37
pubmed: 16771507
Nucleic Acids Res. 2015 Jul 1;43(W1):W225-30
pubmed: 25855813
Chembiochem. 2003 Oct 6;4(10):936-62
pubmed: 14523911
Science. 1990 Aug 3;249(4968):505-10
pubmed: 2200121
Nature. 1990 Aug 30;346(6287):818-22
pubmed: 1697402
J Cheminform. 2012 Aug 13;4(1):17
pubmed: 22889332
Nature. 2002 Jul 11;418(6894):222-8
pubmed: 12110898
Molecules. 2019 Nov 30;24(23):
pubmed: 31801185
Eur Biophys J. 2012 Oct;41(10):789-99
pubmed: 22639100
Nucleic Acids Res. 2021 Aug 20;49(14):e84
pubmed: 34107023
Nat Rev Mol Cell Biol. 2009 Feb;10(2):126-39
pubmed: 19165215
Acta Crystallogr D Struct Biol. 2017 May 1;73(Pt 5):449-464
pubmed: 28471369
J Appl Crystallogr. 2015 Mar 12;48(Pt 2):431-443
pubmed: 25844078
J Mol Graph. 1996 Feb;14(1):33-8, 27-8
pubmed: 8744570
Nature. 2002 Jul 11;418(6894):229-35
pubmed: 12110899
Proc Natl Acad Sci U S A. 2016 Nov 22;113(47):E7456-E7463
pubmed: 27821763
J Biomol Struct Dyn. 2004 Aug;22(1):25-33
pubmed: 15214802
Nat Struct Biol. 1998 Feb;5(2):133-9
pubmed: 9461079
J Biomol Struct Dyn. 2011 Oct;29(2):403-16
pubmed: 21875158
Int J Mol Sci. 2012;13(8):10537-10552
pubmed: 22949878
J Chem Theory Comput. 2015 Aug 11;11(8):3696-713
pubmed: 26574453
Annu Rev Biophys. 2013;42:415-41
pubmed: 23495971
Nature. 2001 Feb 15;409(6822):814-6
pubmed: 11236992
Biophys J. 1999 Jun;76(6):2879-86
pubmed: 10354416
J Chem Theory Comput. 2014 Apr 8;10(4):1518-1537
pubmed: 24803865
J Struct Biol. 2010 Oct;172(1):128-41
pubmed: 20558299
Nucleic Acids Res. 1987 Jan 12;15(1):267-75
pubmed: 3822804
Methods. 2012 May;57(1):11-24
pubmed: 22633887
Biophys Chem. 2016 Mar;210:9-13
pubmed: 26493008
Nucleic Acids Res. 1999 Feb 15;27(4):949-55
pubmed: 9927725
Cell. 2009 Feb 20;136(4):731-45
pubmed: 19239892
Nat Methods. 2016 Jan;13(1):55-8
pubmed: 26569599
Curr Res Struct Biol. 2020 Aug 27;2:164-170
pubmed: 34235476
PLoS Comput Biol. 2020 Apr 27;16(4):e1007870
pubmed: 32339173
J Chem Theory Comput. 2015 Feb 10;11(2):780-7
pubmed: 25688181
Biochemistry (Mosc). 2019 Dec;84(12):1521-1528
pubmed: 31870256
Phys Chem Chem Phys. 2016 Aug 10;18(32):22047-61
pubmed: 27215663
Nucleic Acids Res. 2003 Jul 1;31(13):3406-15
pubmed: 12824337
ChemMedChem. 2020 Feb 17;15(4):363-369
pubmed: 31825565
Cancers (Basel). 2017 Nov 13;9(11):
pubmed: 29137182
Genome Res. 1999 Nov;9(11):1106-15
pubmed: 10568750
Nucleic Acids Res. 2009 Jul;37(12):e87
pubmed: 19465396
RNA. 2005 Jun;11(6):853-63
pubmed: 15923372
RNA. 2002 Jun;8(6):707-17
pubmed: 12088144
J Appl Crystallogr. 2021 Feb 01;54(Pt 1):343-355
pubmed: 33833657
Mol Ther. 2015 Sep;23(9):1486-96
pubmed: 26061649
Hortic Res. 2018 Sep 17;5:63
pubmed: 30245834
Molecules. 2016 Nov 25;21(12):
pubmed: 27898020
Biotechnol J. 2020 Mar;15(3):e1900368
pubmed: 31840436
Angew Chem Int Ed Engl. 2004 Jan;43(2):187-92
pubmed: 14695605
RNA. 1998 Jun;4(6):669-79
pubmed: 9622126
Sci Rep. 2016 Oct 03;6:34350
pubmed: 27694916
Curr Opin Struct Biol. 2004 Jun;14(3):374-9
pubmed: 15193319
J Biomol NMR. 2013 Jun;56(2):95-112
pubmed: 23564038
Protein Sci. 2020 Jan;29(1):66-75
pubmed: 31576635
Bioinformatics. 2018 Jun 1;34(11):1944-1946
pubmed: 29300836
J Chem Theory Comput. 2014 Nov 11;10(11):4801-12
pubmed: 26584367
Nucleic Acids Res. 2008 Jul 1;36(Web Server issue):W163-9
pubmed: 18440976
J Phys Chem B. 2015 Jun 4;119(22):6571-83
pubmed: 25963836
J Appl Crystallogr. 2009 Apr 1;42(Pt 2):342-346
pubmed: 27630371
J Chem Phys. 2020 Apr 21;152(15):154102
pubmed: 32321259
J Chem Phys. 2007 Jan 7;126(1):014101
pubmed: 17212484
Anal Bioanal Chem. 2019 Oct;411(25):6723-6732
pubmed: 31396648
Chembiochem. 2012 Sep 24;13(14):1990-2001
pubmed: 22936620
Proc Natl Acad Sci U S A. 2005 Dec 27;102(52):18902-7
pubmed: 16357200
Nucleic Acids Res. 2012 Sep;40(16):8119-28
pubmed: 22669903