Kinetic coherence underlies the dynamics of disordered proteins

Area of Science:

• Biophysics
• Computational Biology
• Protein Dynamics

Background:

• Understanding protein dynamics is crucial for comprehending their function.
• Coherence time (τ) quantifies the delay in stochastic behavior after perturbation.
• Simulations explore protein states from folded globule to unfolded molten globule.

Purpose of the Study:

• To investigate the dynamics of lysozyme and Huntingtin interacting protein in different conformational states.
• To analyze coherence times in position and momenta subspaces and their principal components.
• To explore the relationship between structural changes (denaturation) and kinetic coherence.

Main Methods:

• Molecular dynamics simulations of lysozyme and Huntingtin interacting protein.
• Calculation of coherence times (τ) using collective variables and principal components (PCs).
• Analysis of coherence times in position (τq) and momenta (τπ) subspaces.

Main Results:

• In all simulated states, τπ ≈ 3.5τq and τπ ≈ 3.5τq.
• Coherence times of individual PCs showed τ(π) > τ(q) across all states.
• Lysozyme denaturation led to decreased τ(q) but increased τ(π), indicating a gain in kinetic coherence.
• This gain in kinetic coherence was specific to lysozyme and not observed in Huntingtin protein.

Conclusions:

• Protein denaturation can lead to a gain in kinetic coherence, a phenomenon observed in functional lysozyme.
• A 'hidden synchronism' enhances momenta subspace coherence, a generic property across various polypeptides.
• The increase in kinetic coherence during denaturation appears specific to biologically functional proteins like lysozyme.