Joshua A Dudley, Sojeong Park, Oliver Cho, Nicholas G M Wells, Meagan E MacDonald, Katerina M Blejec, Emmanuel Fetene, Eric Zanderigo, Scott Houliston, Jennifer C Liddle, Chad M Dashnaw, T Michael Sabo, Bryan F Shaw, Jeremy L Balsbaugh, Gabriel J Rocklin, Colin A Smith
The de novo design of miniprotein inhibitors has recently emerged as a new technology to create proteins that bind with high affinity to specific therapeutic targets. Their size, ease of expression, and apparent high stability makes them excellent candidates for a new class of protein drugs. However, beyond circular dichroism melts and hydrogen/deuterium exchange experiments, little is known about their dynamics, especially at the elevated temperatures they seemingly tolerate quite well. To address that and gain insight for future designs, we have focused on identifying unintended and previously overlooked heat-induced structural and chemical changes in a particularly stable model miniprotein, EHEE_rd2_0005...
June 2024: Protein Science