Conformational relaxation and ligand binding in myoglobin

Area of Science:

• Biophysics
• Protein dynamics
• Spectroscopy

Background:

• Myoglobin's function relies on protein conformational changes.
• Understanding these dynamics is key to protein function.
• Carbon monoxide (CO) is a common ligand studied in myoglobin.

Purpose of the Study:

• To investigate the relationship between myoglobin's conformational relaxation and carbon monoxide (CO) rebinding kinetics.
• To characterize the timescales and molecular basis of these processes.
• To develop and apply advanced kinetic models and numerical techniques.

Main Methods:

• Absorption spectroscopy with nanosecond time resolution.
• Kinetic data analysis using empirical and molecular models.
• Variable temperature and viscosity experiments.
• Singular value decomposition and Monte Carlo methods for data fitting.

Main Results:

• Myoglobin conformational relaxation occurs on the same timescale as geminate CO rebinding.
• Two distinct conformations of myoglobin were identified, differing in CO rebinding rates by over 100-fold.
• The transition rate between conformations is viscosity-dependent, suggesting global protein movements.
• Spectral differences between conformations resemble hemoglobin's R and T states.

Conclusions:

• Conformational changes are intrinsically linked to ligand rebinding in myoglobin.
• The observed conformational relaxation is likely the final stage of a process beginning on the picosecond timescale.
• This relaxation may explain temperature-dependent ligand rebinding phenomena observed in other studies.