Hydrogen bonds vs RMSD: Geometric reaction coordinates for protein folding

Area of Science:

• Computational Biology
• Biophysics
• Molecular Dynamics

Background:

• Reaction coordinates simplify complex protein dynamics by reducing high-dimensional phase space to fewer degrees of freedom.
• These coordinates aid in understanding protein dynamics, calculating transition rates, and sampling phase space efficiently with molecular dynamics (MD) simulations.
• Ideal reaction coordinates are not known a priori, making their efficient calculation during MD simulations an active research area.

Purpose of the Study:

• To compare the effectiveness of five geometric reaction coordinates in analyzing protein dynamics.
• To evaluate the utility of these coordinates in calculating free energy profiles for peptides and a small protein.
• To identify which geometric reaction coordinates provide the most insightful analysis of protein conformational changes.

Main Methods:

• Extensive molecular dynamics (MD) simulations were performed on two peptides and a small protein.
• Five geometric reaction coordinates were investigated: end-to-end distance, radius of gyration, solvent accessible surface area, root-mean-square distance (RMSD), and mean native hydrogen bond length.
• Free energy profiles were calculated and compared using these reaction coordinates.

Main Results:

• None of the tested geometric reaction coordinates proved to be optimal.
• The root-mean-square distance (RMSD) and mean native hydrogen bond length demonstrated superior performance compared to the other three investigated coordinates.
• These findings suggest RMSD and mean native hydrogen bond length are more effective for simplified mechanistic models of protein dynamics.

Conclusions:

• Geometric reaction coordinates offer a simplified approach to understanding protein dynamics, despite limitations in quantitative accuracy.
• RMSD and mean native hydrogen bond length are more effective than end-to-end distance, radius of gyration, and solvent accessible surface area for analyzing protein conformational changes.
• Further research into optimizing reaction coordinate selection can enhance the study of protein dynamics and mechanisms.