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Free-energy barriers in MbCO rebinding.
Polina Banushkina1, Markus Meuwly
1Department of Chemistry, University of Basel, Klingelbergstrasse 80, 4056 Basel, Switzerland.
The Journal of Physical Chemistry. B
|July 21, 2006
Summary
We studied carbon monoxide (CO) rebinding to myoglobin (Mb) using simulations. Native Mb shows barriers consistent with experiments, while the L29F mutant exhibits faster dynamics and easier ligand escape.
Area of Science:
- Biophysics
- Computational Chemistry
- Molecular Dynamics
Background:
- Myoglobin (Mb) is crucial for oxygen transport.
- Understanding ligand rebinding dynamics in Mb is key to protein function.
- The L29F mutation alters Mb's active site environment.
Purpose of the Study:
- To investigate the rebinding of carbon monoxide (CO) to native and L29F mutant myoglobin (Mb).
- To characterize the free-energy landscape and barriers governing CO escape and rebinding.
- To compare simulation results with experimental data for validation.
Main Methods:
- Combined molecular dynamics and stochastic simulations.
- Utilized a fluctuating three-point charge model for CO.
- Employed umbrella sampling and the Smoluchowski equation for free-energy profile construction.
Main Results:
- Simulated rebinding times for native Mb align well with experimental values.
- Identified distinct energy barriers for CO rebinding in native Mb (e.g., 4.3 kcal/mol inner barrier).
- L29F mutant shows a flatter free-energy surface, faster dynamics, and facile escape to the Xe4 pocket.
Conclusions:
- The computational model accurately captures CO rebinding dynamics in myoglobin.
- The L29F mutation significantly alters the protein-ligand interaction landscape.
- Temperature dependence plays a critical role in myoglobin-ligand rebinding kinetics.