Microsecond folding experiments and simulations: a match is made.

Area of Science:

• Biophysics
• Computational Biology
• Biochemistry

Background:

• Protein folding experiments have accelerated from millisecond to microsecond timescales over two decades.
• Full-atom simulations have advanced from nanoseconds to microseconds and milliseconds.
• The convergence of experimental and simulation timescales enables direct comparison and validation.

Purpose of the Study:

• To compare recent microsecond-timescale experiments and simulations in protein folding.
• To highlight progress in determining native protein structures using physics-based simulations.
• To discuss the refinement of experiments and simulations for quantitative mechanistic insights.

Main Methods:

• Comparison of microsecond-timescale experimental data with full-atom simulations.
• Validation and refinement of protein force fields using experimental data.
• Atomistic interpretation of experimental results through simulation.

Main Results:

• Direct comparison of experiments and simulations is now feasible at the microsecond scale.
• Progress in determining native structures from physics-based simulations.
• Enhanced quantitative understanding of underlying folding mechanisms.

Conclusions:

• The meeting of experimental and simulation timescales significantly advances protein folding research.
• This synergy allows for robust validation of computational models and detailed interpretation of experimental findings.
• Future research can better address complex challenges like multiple reaction coordinates and unfolded/misfolded state structures.