It is theoretically possible to avoid misfolding into non-covalent lasso entanglements using small molecule drugs.

ABSTRACT: A novel class of protein misfolding characterized by either the formation of non-native noncovalent lasso entanglements in the misfolded structure or loss of native entanglements has been predicted to exist and found circumstantial support through biochemical assays and limited-proteolysis mass spectrometry data. Here, we examine whether it is possible to design small molecule compounds that can bind to specific folding intermediates and thereby avoid these misfolded states in computer simulations under idealized conditions (perfect drug-binding specificity, zero promiscuity, and a smooth energy landscape). Studying two proteins, type III chloramphenicol acetyltransferase (CAT-III) and D-alanyl-D-alanine ligase B (DDLB), that were previously suggested to form soluble misfolded states throu

SUBMITTER: Jiang Y 

PROVIDER: S-EPMC10931463 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature