.png){kind=icon}
返回
Decoding CRISPR-Cas PAM recognition with UniDesign
.png){kind=icon}
OA
AI
DOI：10.1093/bib/bbad133.png)
.png){kind=icon}
原文求助.png){kind=icon}
分享.png){kind=icon}
收藏
摘要
En 中文
The critical first step in Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)associated (CRISPRCas) protein-mediated gene editing is recognizing a preferred protospacer adjacent motif (PAM) on target DNAs by the proteins PAM-interacting amino acids (PIAAs). Thus, accurate computational modeling of PAM recognition is useful in assisting CRISPRCas engineering to relax or tighten PAM requirements for subsequent applications. Here, we describe a universal computational protein design framework (UniDesign) for designing proteinnucleic acid interactions. As a proof of concept, we applied UniDesign to decode the PAMPIAA interactions for eight Cas9 and two Cas12a proteins. We show that, given native PIAAs, the UniDesign-predicted PAMs are largely identical to the natural PAMs of all Cas proteins. In turn, given natural PAMs, the computationally redesigned PIAA residues largely recapitulated the native PIAAs (74% and 86% in terms of identity and similarity, respectively). These results demonstrate that UniDesign faithfully captures the mutual preference between natural PAMs and native PIAAs, suggesting it is a useful tool for engineering CRISPRCas and other nucleic acid-interacting proteins. UniDesign is open-sourced at https://github.com/tommyhuangthu/UniDesign.
Keyword:
CRISPR-Cas
PAM
gene editing
computational protein design
UniDesign
期刊
IF:
7.7
论文数:
5.8K
被引数:
2.7W
机构
引用论文
The Neisseria meningitidis CRISPR-Cas9 System Enables Specific Genome Editing in Mammalian Cells
OAAI
OAAI分享收藏分享收藏分享收藏Crystal Structure of the Minimal Cas9 from Campylobacter jejuni Reveals the Molecular Diversity in the CRISPR-Cas9 Systems.png)
MOLECULAR CELLOAAI
MOLECULAR CELLIF16.6
OAAI分享收藏Automated Structure- and Sequence-Based Design of Proteins for High Bacterial Expression and Stability基于结构和序列的蛋白质的自动化设计，以实现高细菌表达和稳定性MOLECULAR CELLOAAI
MOLECULAR CELLIF16.6
OAAI分享收藏The molecular basis for recognition of 5′-NNNCC-3′ PAM and its methylation state by Acidothermus cellulolyticus Cas9NATURE COMMUNICATIONSOAAI
NATURE COMMUNICATIONSIF15.7
OAAI分享收藏
查看更多内容