Computational design of sequence-specific DNA-binding proteins.

ABSTRACT: Sequence-specific DNA-binding proteins (DBPs) play critical roles in biology and biotechnology, and there has been considerable interest in the engineering of DBPs with new or altered specificities for genome editing and other applications. While there has been some success in reprogramming naturally occurring DBPs using selection methods, the computational design of new DBPs that recognize arbitrary target sites remains an outstanding challenge. We describe a computational method for the design of small DBPs that recognize specific target sequences through interactions with bases in the major groove, and employ this method in conjunction with experimental screening to generate binders for 5 distinct DNA targets. These binders exhibit specificity closely matching the computational models f

SUBMITTER: Glasscock CJ 

PROVIDER: S-EPMC10542524 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature