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

Polina V. Zhdanova, Alexander A. Lomzov, Daria V. Prokhorova, Grigory A. Stepanov, Alexander A. Chernonosov, Vladimir V. Koval

Результат исследования: Научные публикации в периодических изданияхстатьярецензирование

Аннотация

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.

Язык оригиналаанглийский
Номер статьи8891
ЖурналInternational Journal of Molecular Sciences
Том23
Номер выпуска16
DOI
СостояниеОпубликовано - 10 авг. 2022

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