title: Structural Dynamics of Thrombin-Binding DNA Aptamer d(GGTTGGTGTGGTTGG) Quadruplex DNA Studied by Large-Scale Explicit Solvent Simulations.
abstract: The thrombin-binding aptamer (15-TBA) is a 15-mer DNA oligonucleotide with sequence d(GGTTGGTGTGGTTGG). 15-TBA folds into a quadruplex DNA (G-DNA) structure with two planar G-quartets connected by three single-stranded loops. The arrangement of the 15-TBA-thrombin complex is unclear, particularly with respect to the precise 15-TBA residues that interact with the thrombin structure. Our present understanding suggests either the 15-TBA single stranded loops containing sequential thymidines (TT) or alternatively a single-stranded loop, containing a guanine flanked by 2 thymidines (TGT), physically associates with thrombin protein. In the present study, the explicit solvent molecular dynamics (MD) simulation method was utilized to further analyze the 15-TBA-thrombin three-dimensional structure. Functional annotation of the loop residues was made with long simulations in the parmbsc0 force field. In total, the elapsed time of simulations carried out in this study exceeds 12 microseconds, substantially surpassing previous G-DNA simulation reports. Our simulations suggest that the TGT-loop function is to stabilize the structure of the aptamer, while the TT-loops participate in direct binding to thrombin. The findings of the present report advance our understanding of the molecular structure of the 15-TBA-thrombin structure further enabling the construction of biosensors for aptamer bases and the development of anticoagulant agents.
authors.affiliation: Department of Boiengineering and Bioinformatics, Lomonosov Moscow State University, GSP-1, Leninskie Gory, Moscow, 119991, Russian Federation.|Department of Boiengineering and Bioinformatics, Lomonosov Moscow State University, GSP-1, Leninskie Gory, Moscow, 119991, Russian Federation.|A.N.Belozersky Institute of Physical Chemical Biology, Lomonosov Moscow State University, GSP-1, Leninskie Gory, Moscow, 119991, Russian Federation.|Chemistry Department, Lomonosov Moscow State University, Gsp-1, Leninskie Gory, Moscow, 119991, Russian Federation.|Institute of Biophysics, Academy of Sciences of the Czech Republic, Královopolská 135, 61265 Brno, Czech Republic.
authors.forename: Roman
authors.initials: R
authors.lastname: Reshetnikov
authors.affiliation: Department of Boiengineering and Bioinformatics, Lomonosov Moscow State University, GSP-1, Leninskie Gory, Moscow, 119991, Russian Federation.|Department of Boiengineering and Bioinformatics, Lomonosov Moscow State University, GSP-1, Leninskie Gory, Moscow, 119991, Russian Federation.|A.N.Belozersky Institute of Physical Chemical Biology, Lomonosov Moscow State University, GSP-1, Leninskie Gory, Moscow, 119991, Russian Federation.|Chemistry Department, Lomonosov Moscow State University, Gsp-1, Leninskie Gory, Moscow, 119991, Russian Federation.|Institute of Biophysics, Academy of Sciences of the Czech Republic, Královopolská 135, 61265 Brno, Czech Republic.
authors.forename: Andrey
authors.initials: A
authors.lastname: Golovin
authors.affiliation: Department of Boiengineering and Bioinformatics, Lomonosov Moscow State University, GSP-1, Leninskie Gory, Moscow, 119991, Russian Federation.|Department of Boiengineering and Bioinformatics, Lomonosov Moscow State University, GSP-1, Leninskie Gory, Moscow, 119991, Russian Federation.|A.N.Belozersky Institute of Physical Chemical Biology, Lomonosov Moscow State University, GSP-1, Leninskie Gory, Moscow, 119991, Russian Federation.|Chemistry Department, Lomonosov Moscow State University, Gsp-1, Leninskie Gory, Moscow, 119991, Russian Federation.|Institute of Biophysics, Academy of Sciences of the Czech Republic, Královopolská 135, 61265 Brno, Czech Republic.
authors.forename: Vera
authors.initials: V
authors.lastname: Spiridonova
authors.affiliation: Department of Boiengineering and Bioinformatics, Lomonosov Moscow State University, GSP-1, Leninskie Gory, Moscow, 119991, Russian Federation.|Department of Boiengineering and Bioinformatics, Lomonosov Moscow State University, GSP-1, Leninskie Gory, Moscow, 119991, Russian Federation.|A.N.Belozersky Institute of Physical Chemical Biology, Lomonosov Moscow State University, GSP-1, Leninskie Gory, Moscow, 119991, Russian Federation.|Chemistry Department, Lomonosov Moscow State University, Gsp-1, Leninskie Gory, Moscow, 119991, Russian Federation.|Institute of Biophysics, Academy of Sciences of the Czech Republic, Královopolská 135, 61265 Brno, Czech Republic.
authors.forename: Alexei
authors.initials: A
authors.lastname: Kopylov
authors.affiliation: Department of Boiengineering and Bioinformatics, Lomonosov Moscow State University, GSP-1, Leninskie Gory, Moscow, 119991, Russian Federation.|Department of Boiengineering and Bioinformatics, Lomonosov Moscow State University, GSP-1, Leninskie Gory, Moscow, 119991, Russian Federation.|A.N.Belozersky Institute of Physical Chemical Biology, Lomonosov Moscow State University, GSP-1, Leninskie Gory, Moscow, 119991, Russian Federation.|Chemistry Department, Lomonosov Moscow State University, Gsp-1, Leninskie Gory, Moscow, 119991, Russian Federation.|Institute of Biophysics, Academy of Sciences of the Czech Republic, Královopolská 135, 61265 Brno, Czech Republic.
authors.forename: Jiří
authors.initials: J
authors.lastname: Šponer