Research output: Contribution to journal › Article › peer-review
Thermodynamic Swings: How Ideal Complex of Cas9-RNA/DNA Forms. / Zhdanova, Polina V.; Lomzov, Alexander A.; Prokhorova, Daria V. et al.
In: International Journal of Molecular Sciences, Vol. 23, No. 16, 8891, 10.08.2022.Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - Thermodynamic Swings: How Ideal Complex of Cas9-RNA/DNA Forms
AU - Zhdanova, Polina V.
AU - Lomzov, Alexander A.
AU - Prokhorova, Daria V.
AU - Stepanov, Grigory A.
AU - Chernonosov, Alexander A.
AU - Koval, Vladimir V.
N1 - Publisher Copyright: © 2022 by the authors.
PY - 2022/8/10
Y1 - 2022/8/10
N2 - Most processes of the recognition and formation of specific complexes in living systems begin with collisions in solutions or quasi-solutions. Then, the thermodynamic regulation of complex formation and fine tuning of complexes come into play. Precise regulation is very important in all cellular processes, including genome editing using the CRISPR-Cas9 tool. The Cas9 endonuclease is an essential component of the CRISPR-Cas-based genome editing systems. The attainment of high-specificity and -efficiency Cas9 during targeted DNA cleavage is the main problem that limits the practical application of the CRISPR-Cas9 system. In this study, we analyzed the thermodynamics of interaction of a complex's components of Cas9-RNA/DNA through experimental and computer simulation methods. We found that there is a small energetic preference during Cas9-RNA/DNA formation from the Cas9-RNA and DNA/DNA duplex. The small difference in binding energy is relevant for biological interactions and could be part of the sequence-specific recognition of double-stranded DNA by the CRISPR-Cas9 system.
AB - Most processes of the recognition and formation of specific complexes in living systems begin with collisions in solutions or quasi-solutions. Then, the thermodynamic regulation of complex formation and fine tuning of complexes come into play. Precise regulation is very important in all cellular processes, including genome editing using the CRISPR-Cas9 tool. The Cas9 endonuclease is an essential component of the CRISPR-Cas-based genome editing systems. The attainment of high-specificity and -efficiency Cas9 during targeted DNA cleavage is the main problem that limits the practical application of the CRISPR-Cas9 system. In this study, we analyzed the thermodynamics of interaction of a complex's components of Cas9-RNA/DNA through experimental and computer simulation methods. We found that there is a small energetic preference during Cas9-RNA/DNA formation from the Cas9-RNA and DNA/DNA duplex. The small difference in binding energy is relevant for biological interactions and could be part of the sequence-specific recognition of double-stranded DNA by the CRISPR-Cas9 system.
KW - Cas9
KW - CRISPR–Cas systems
KW - ITC
KW - molecular dynamics
KW - single-guide RNA
KW - thermodynamics
UR - http://www.scopus.com/inward/record.url?scp=85137125956&partnerID=8YFLogxK
U2 - 10.3390/ijms23168891
DO - 10.3390/ijms23168891
M3 - Article
C2 - 36012157
AN - SCOPUS:85137125956
VL - 23
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
SN - 1661-6596
IS - 16
M1 - 8891
ER -
ID: 37098243