Computational design of sequence-specific DNA-binding proteins.

ABSTRACT: Sequence-specific DNA-binding proteins (DBPs) have 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 short specific target sequences through interactions with bases in the major groove and use this method to generate binders for five distinct DNA targets with mid-nanomolar to high-nanomolar affinities. The individual binding modules have specificity closely matching the

SUBMITTER: Glasscock CJ 

PROVIDER: S-EPMC12618268 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature