Universality of fold-encoded localized vibrations in enzymes

Area of Science:

• Biochemistry
• Structural Biology
• Computational Biology

Background:

• Enzymes are crucial biological catalysts accelerating reactions by up to 15 orders of magnitude.
• The precise microscopic mechanisms underlying enzyme catalytic efficiency remain incompletely understood.
• Understanding enzyme dynamics is key to deciphering their structure-function relationship.

Purpose of the Study:

• To elucidate the microscopic dynamical determinants of enzyme catalytic proficiency.
• To investigate the role of vibrations in enzyme-catalyzed reactions.
• To uncover the relationship between protein structure, dynamics, and function.

Main Methods:

• Utilized a sophisticated mathematical approach to analyze enzyme dynamics.
• Investigated picosecond-range vibrations encoded within the 3D protein structure.
• Examined the coupling of vibrations to chemical reaction coordinates at the active site.

Main Results:

• Identified rate-promoting vibrations, localized and optimally coupled to reaction coordinates.
• Discovered a novel link between vibration localization and protein subdomain partitioning.
• Demonstrated universality across over 900 enzyme structures (10,000+ catalytic sites).

Conclusions:

• Enzyme catalysis is governed by specific, localized, picosecond-range vibrations.
• Protein structure partitions into subdomains facilitating long-range communication and enzyme function.
• Provides a unified microscopic explanation for the enzyme structure-dynamics-function link.