Targeted Protein Degradation: Advances, Challenges, and Prospects for Computational Methods.

ABSTRACT: The therapeutic approach of targeted protein degradation (TPD) is gaining momentum due to its potentially superior effects compared with protein inhibition. Recent advancements in the biotech and pharmaceutical sectors have led to the development of compounds that are currently in human trials, with some showing promising clinical results. However, the use of computational tools in TPD is still limited, as it has distinct characteristics compared with traditional computational drug design methods. TPD involves creating a ternary structure (protein-degrader-ligase) responsible for the biological function, such as ubiquitination and subsequent proteasomal degradation, which depends on the spatial orientation of the protein of interest (POI) relative to E2-loaded ubiquitin. Modeling this stru

SUBMITTER: Mostofian B 

PROVIDER: S-EPMC10498452 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature