Thermodynamic Swings: How Ideal Complex of Cas9-RNA/DNA Forms

Thermodynamic Swings: How Ideal Complex of Cas9-RNA/DNA Forms Full article

Journal

International Journal of Molecular Sciences
, E-ISSN: 1422-0067

Output data

Year: 2022, Volume: 23, Number: 16, DOI: 10.3390/ijms23168891

Tags

Cas9; CRISPR–Cas systems; ITC; molecular dynamics; single-guide RNA; thermodynamics

Authors

Zhdanova P.V. ^1,2 , Lomzov A.A. ^1,2 , Prokhorova D.V. ¹ , Stepanov G.A. ¹ , Chernonosov A.A. ¹ , Koval V.V. ^1,2

Affiliations

1	Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences (SB RAS), Novosibirsk, 630090, Russian Federation
2	Department of Natural Sciences, Novosibirsk State University, Novosibirsk, 630090, Russian Federation

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.

Zhdanova P.V. , Lomzov A.A. , Prokhorova D.V. , Stepanov G.A. , Chernonosov A.A. , Koval V.V.
Thermodynamic Swings: How Ideal Complex of Cas9-RNA/DNA Forms
International Journal of Molecular Sciences. 2022. V.23. N16. DOI: 10.3390/ijms23168891 WOS Scopus OpenAlex

Published print:

Aug 10, 2022

Web of science:	WOS:000846651600001
Scopus:	2-s2.0-85137125956
OpenAlex:	W4293680663

DB	Citing
Scopus	1
OpenAlex	2
Web of science	3