Energetic conflicts in catalytic sites of protein enzymes

LUNA, DIEGO; GUZOVSKY, ANA BRENDA; FREIBERGER, MARIA I.; WOLYNES, PETER G.

Conferencia; 27 Intelligent Systems for Molecular Biology/ 18 European Conference on Computational Biology 2019; 2019

IntroductionWhile proteins fold, strong energetic conflicts are minimized towards their native states according to the principle of minimal frustration. Local violations of this principle allow proteins to encode the complex energy landscapes, required for active biological functions. Enzymatic reaction rates strongly depend on precise and conserved arrangements bringing together in space residues that would otherwise adopt different interactions. Hence, catalytic sites are expected to be locally frustrated.ResultsWe quantified local energetic conflicts of all protein enzymes with known structures and experimentally annotated catalytic residues. Catalytic sites are effectively highly frustrated in extant enzymes, regardless of protein oligomeric state, topology, and enzymatic class. We show that, in the context of protein families, frustration at catalytic sites is more evolutionarily conserved than the primary structure itself (Freiberger et. al, PNAS 2019). Additionally, we will also discuss the appearance of specific frustration patterns along the evolutionary history of protein superfamilies.