Dynamical theory of activated processes in globular proteins

Area of Science:

• Biophysics
• Computational Chemistry
• Biochemistry

Background:

• Globular proteins facilitate crucial biological processes like ligand binding and enzymatic catalysis.
• Accurate calculation of reaction rates within proteins is essential for understanding these processes.
• Existing methods often struggle to precisely model the complex dynamics of protein reactions.

Purpose of the Study:

• To introduce a novel computational method for determining reaction rates in globular proteins.
• To assess the feasibility of calculating rate constants for protein-bound reactions.
• To investigate the influence of solvent effects on reactions occurring at the protein surface.

Main Methods:

• The method combines the determination of transition-state probability with the calculation of reactive flux.
• Umbrella sampling simulations are employed to evaluate the transition-state probability.
• Previously established approaches are used to compute the dynamics of transition-state trajectories.

Main Results:

• The study successfully applied the method to calculate the rate constant for rotational isomerization in the bovine pancreatic trypsin inhibitor.
• Results demonstrate the feasibility of calculating reaction rates for processes within proteins.
• Solvent effects were identified as significant for reactions occurring near the protein surface.

Conclusions:

• The presented method offers a viable approach for calculating reaction rates in globular proteins.
• Understanding solvent-protein interactions is critical for accurately modeling surface-localized protein reactions.
• This work paves the way for more precise predictions of protein-mediated reaction kinetics.