Structural Characterization of λ-Repressor Folding from All-Atom Molecular Dynamics Simulations

Area of Science:

• Biophysics
• Computational Biology
• Protein Dynamics

Background:

• The lambda-repressor fragment is an 80-amino acid fast-folding protein.
• Its size presents computational challenges for molecular dynamics (MD) studies.

Purpose of the Study:

• To simulate the folding and unfolding of a novel lambda-repressor fast-folding mutant (λ-HG) in explicit solvent.
• To investigate the folding kinetics using extensive molecular dynamics simulations.

Main Methods:

• Employed an all-atom description for molecular dynamics simulations.
• Utilized a novel tempering method to observe reversible folding and unfolding.
• Conducted extensive MD simulations exceeding 125 microseconds across various temperatures.

Main Results:

• Observed reversible folding and unfolding of the lambda-repressor fragment within a 10-microsecond trajectory.
• Identified a slow-folding pathway at intermediate temperatures.
• The protein adopted a native-like topology under simulated conditions.

Conclusions:

• The study provides insights into the folding kinetics of fast-folding proteins.
• Suggests new experimental observables for monitoring protein folding.
• Proposes a novel mutation to potentially accelerate lambda-repressor folding.