Unveiling New Strategies to Target and Inhibit KRAS in Cancer

Researchers have created multiple global atlases of inhibitory allosteric communication in KRAS, a protein involved in signaling pathways and a known therapeutic target. By quantifying the impact of over 26,000 mutations on the folding and binding of KRAS, the study identified allosteric sites that can be targeted for inhibition. The central beta sheet of KRAS was found to be particularly effective in allosteric propagation, and multiple surface pockets were validated as allosterically active, including a distal pocket in the C-terminal lobe of the protein. This research provides insights into the regulatory and therapeutic potential of allosteric modulation in proteins.