Protein Structure Inspired Discovery of a Novel Inducer of Anoikis in Human Melanoma.

ABSTRACT: Drug discovery historically starts with an established function, either that of compounds or proteins. This can hamper discovery of novel therapeutics. As structure determines function, we hypothesized that unique 3D protein structures constitute primary data that can inform novel discovery. Using a computationally intensive physics-based analytical platform operating at supercomputing speeds, we probed a high-resolution protein X-ray crystallographic library developed by us. For each of the eight identified novel 3D structures, we analyzed binding of sixty million compounds. Top-ranking compounds were acquired and screened for efficacy against breast, prostate, colon, or lung cancer, and for toxicity on normal human bone marrow stem cells, both using eight-day colony formation assays. Eff

SUBMITTER: Qiao F 

PROVIDER: S-EPMC11429909 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature