#24 · Structural bio & protein design

Protonation, hydration and conformation gate enzyme and motor state switching

The dominant thread is that function depends on the distribution of conformational and protonation states rather than a single static structure. In xanthan glycosyltransferase GumK, AI-based docking with GNINA and AlphaFold3/Boltz cofolding ensembles links conformation to donor selectivity, though this is docking-based rather than direct transition mapping. Constant-pH MD and FEP/pKa calculations on C. jejuni MotAB show asymmetric D22 hydration and protonation switching of dual aspartates driving flagellar rotation. For SARS-CoV-2 nsp16, MD and AI/ML suggest nsp10 activates the enzyme via a hydrophobic latch, while monomeric nsp16 closes its SAM pocket. QM/MM metadynamics and umbrella sampling map the PL42 lyase beta-elimination free-energy surface, implicating His85. What is new is explicit treatment of protonation, hydration, and conformational gating as state-switching elements.