Pressure-Dependent Conformation and Fluctuation in Folded Protein Molecules

Area of Science:

• Biophysics
• Structural Biology
• Protein Dynamics

Background:

• Proteins undergo structural fluctuations at ambient conditions.
• Understanding how external factors like pressure influence these dynamics is crucial for deciphering protein function.

Purpose of the Study:

• To investigate the effects of hydrostatic pressure on protein structure and dynamics.
• To characterize pressure-induced changes in protein fluctuations and their functional implications.

Main Methods:

• Analysis of protein structural changes under varying hydrostatic pressures.
• Examination of hydrogen bond compression and distortion of secondary structures (sheets vs. helices).
• Study of pressure effects on protein fluctuation timescales and populations of excited states.

Main Results:

• Proteins exhibit nonuniform compression under pressure, with larger effects near cavities and buried water.
• Secondary structures like sheets distort more than helices; hydrogen bonds compress slightly.
• Pressure primarily affects slower, larger-scale motions, increasing the population of low-volume excited states and slowing fluctuations.
• In barnase, pressure reveals hierarchical microsecond-timescale fluctuations, suggesting faster motions enable slower ones.

Conclusions:

• Hydrostatic pressure is a valuable tool for probing hierarchical protein dynamics.
• Pressure-induced population of excited states may be functionally relevant.
• Protein structural responses to pressure offer insights into their intrinsic flexibility and functional mechanisms.