Документ взят из кэша поисковой машины. Адрес оригинального документа : http://dualopt1.cmm.msu.ru/pub/Projects/ParmBsc0/jctc.ciw Дата изменения: Wed Apr 18 20:48:03 2012 Дата индексирования: Fri Feb 28 20:20:08 2014 Кодировка:

FN Thomson Reuters Web of Knowledge
VR 1.0
PT J
AU Reshetnikov, R
Golovin, A
Spiridonova, V
Kopylov, A
Sponer, J
AF Reshetnikov, Roman
Golovin, Andrey
Spiridonova, Vera
Kopylov, Alexei
Sponer, Jiri
TI Structural Dynamics of Thrombin-Binding DNA Aptamer d(GGTTGGTGTGGTTGG)
Quadruplex DNA Studied by Large-Scale Explicit Solvent Simulations
SO JOURNAL OF CHEMICAL THEORY AND COMPUTATION
LA English
DT Article
ID DENSITY-FUNCTIONAL THEORY; MOLECULAR-DYNAMICS; FORCE-FIELD;
THERMODYNAMIC ANALYSIS; STABILITY; COMPLEX; ALGORITHM; EVOLUTION;
ENERGIES
AB 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.
[GRAPHICS]
.
C1 [Reshetnikov, Roman; Golovin, Andrey] Moscow MV Lomonosov State Univ, Dept Boiengn & Bioinformat, Moscow 119991, Russia.
[Spiridonova, Vera] Moscow MV Lomonosov State Univ, AN Belozersky Inst Phys Chem Biol, Moscow 119991, Russia.
[Kopylov, Alexei] Moscow MV Lomonosov State Univ, Dept Chem, Moscow 119991, Russia.
[Sponer, Jiri] Acad Sci Czech Republic, Inst Biophys, Brno 61265, Czech Republic.
RP Reshetnikov, R (reprint author), Moscow MV Lomonosov State Univ, Dept Boiengn & Bioinformat, GSP-1, Moscow 119991, Russia
EM r.reshetnikov@gmail.com
FU Grant Agency of the Academy of Sciences of the Czech
Republic[IAA400040802]; Grant Agency of the Czech Republic[203/09/1476];
Ministry of Education of the Czech Republic[LC06030]; Academy of
Sciences of the Czech Republic[AV0Z50040507, AV0Z50040702]; Russian
Foundation for Basic Research[08-04-01244-a, 08-04-01540-a]; Ministry of
Education and Science of the Russian Federation[02.512.11.2242]
FX Computer resources were provided by the Research Computing Center of
Moscow State University. The supercomputer, "Chebyshev", was used for
all modeling studies. J.S. was supported by the Grant Agency of the
Academy of Sciences of the Czech Republic grant IAA400040802, Grant
Agency of the Czech Republic grant 203/09/1476, Ministry of Education of
the Czech Republic grant LC06030 and Academy of Sciences of the Czech
Republic, Grants AV0Z50040507 and AV0Z50040702. R.R. is grateful to
Arthur Zalevsky for his help in the preparation of simulations. This
research was also supported by Russian Foundation for Basic Research
Grants 08-04-01244-a and 08-04-01540-a and Ministry of Education and
Science of the Russian Federation Grant 02.512.11.2242.
NR 51
TC 3
Z9 3
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1549-9618
J9 J CHEM THEORY COMPUT
JI J. Chem. Theory Comput.
PD OCT
PY 2010
VL 6
IS 10
BP 3003
EP 3014
DI 10.1021/ct100253m
PG 12
WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical
SC Chemistry; Physics
GA 662UX
UT WOS:000282840600001
ER
EF