Protein folding by zipping and assembly.

Area of Science:

• Biophysics
• Computational Biology
• Protein Folding

Background:

• Proteins fold into functional native structures rapidly, often in microseconds.
• Understanding protein folding mechanisms is crucial for predicting protein structures.
• Current atomically detailed physical models face challenges in protein structure prediction.

Purpose of the Study:

• To test the zipping and assembly (ZA) mechanism as a model for rapid protein folding.
• To assess the efficacy of the ZA method in predicting native protein structures using physics-based models.
• To determine if physics-based protein structure prediction is practical for small proteins.

Main Methods:

• Applied the zipping and assembly (ZA) search mechanism to protein native structure prediction.
• Utilized the AMBER96 force field with a generalized Born/surface area implicit solvent model.
• Employed replica exchange molecular dynamics for conformational sampling.

Main Results:

• The ZA method converged to an average of 2.2 Å from native structures for eight of nine tested proteins (25–73 amino acids).
• Predicted folding routes were consistent with available experimental Phi values.
• Demonstrated the viability of the ZA mechanism for modeling protein folding.

Conclusions:

• The zipping and assembly (ZA) mechanism is a viable model for how proteins physically fold.
• Physics-based force fields are effective for protein structure prediction.
• Physics-based protein structure prediction shows practical potential, especially for smaller proteins.