Time-resolved observation of protein allosteric communication

Area of Science:

• Biophysics
• Structural Biology
• Computational Biology

Background:

• Allostery is a key biological regulatory mechanism involving communication between distant protein sites.
• The dynamics of allosteric transitions are not well understood.
• Time-resolved infrared spectroscopy suggested multiple timescales for allosteric transitions in PDZ2S.

Purpose of the Study:

• To develop a time-dependent picture of allosteric communication in the photoswitchable PDZ2S domain.
• To investigate the nonlinear and nonlocal nature of allosteric signal propagation.
• To construct a dynamic network model illustrating the allosteric process hierarchy.

Main Methods:

• Extensive nonequilibrium molecular dynamics simulations.
• Development of a dynamic network model.
• Comparison with experimental data from time-resolved infrared spectroscopy.

Main Results:

• Allosteric communication involves genuinely nonlinear and nonlocal propagation of structural and dynamical changes.
• A dynamic network model revealed the process's hierarchy and heterogeneity.
• Three distinct temporal phases were identified: elastic response (nanoseconds), inelastic reorganization (nanoseconds), and structural relaxation (seconds).

Conclusions:

• The study provides a detailed, time-dependent view of allosteric communication in PDZ2S.
• The findings align with experimental observations, validating the simulation approach.
• The research offers insights into allosteric pathways and their relation to protein dynamics, including similarities to downhill folding.