#38 · Structural bio & protein design

Simulations link confinement, condensate solvation and proton switching to function

The dominant thread is that local environment sets the protonation and conformational states that govern molecular behaviour, probed by simulation across scales. Coarse-grained work extends Helical Coherence Theory to multi-persistence-length dsDNA under spherical confinement, reporting non-monotonic, ion-dependent pairing dynamics relevant to homologous gene pairing. All-atom constant-pH molecular dynamics of phase-separated condensates finds protonated states favoured, shifting residue pKa values relative to bulk solvent. Simulations of respiratory complex I show histidine switch dynamics coupled to lysine charge states, which may gate proton transfer. What is new across these studies is the explicit treatment of confinement, condensate solvation and charge-state coupling as direct modulators of molecular behaviour rather than fixed backdrop. The thread is not uniform: the DNA study addresses ion-dependent geometry, while the other two address protonation.