Dynamics of Disordered Proteins under Confinement: Memory Effects and Internal Friction

Area of Science:

• Biophysics
• Computational Biology
• Protein Dynamics

Background:

• Many proteins function as intrinsically disordered proteins (IDPs) under physiological conditions.
• Protein dynamics, including target search and folding upon binding, are critical for function.
• The nature of internal friction in unfolded proteins remains a subject of debate.

Purpose of the Study:

• To investigate the effects of confinement on the dynamics and internal friction of disordered peptides.
• To understand how induced compactness influences protein reconfiguration timescales and relaxation spectra.

Main Methods:

• Systematic atomistic molecular simulations of disordered peptides under varying degrees of confinement.
• Analysis of peptide reconfiguration timescales and relaxation time distributions.

Main Results:

• Confinement leads to an exponential increase in average peptide reconfiguration timescales as spatial dimensions decrease.
• Confinement broadens the spectrum of relaxation timescales, introducing long-tailed distributions.
• The observed dynamics deviate from predictions of standard Rouse and Zimm models.

Conclusions:

• Confinement significantly alters protein dynamics, increasing reconfiguration times and broadening relaxation spectra.
• The broadening of relaxation times necessitates more general models beyond standard Rouse/Zimm models for protein dynamics.
• Anomalous diffusion effects in intramolecular distances should be considered when interpreting experimental data.