Why RMSD Alone Is Not Enough to Prove Protein Stability

By BioDockify Computational Research Team · August 9, 2026 · MD Analysis

A critical analysis of RMSD limitations for stability assessment. Explains why RMSD can be misleading and why multiple metrics must be used together.

Read the complete article with tables, code and references on BioDockify.

Key References

• Kuzmanic, A. & Zagrovic, B. Effects of increased sampling on protein molecular dynamics. J. Phys. Chem. B 114, 7745-7751 (2010).
• Maiorov, V.N. & Crippen, G.M. Significance of root-mean-square deviation in comparing three-dimensional structures. J. Mol. Biol. 235, 625-634 (1994).
• Kufareva, I. & Abagyan, R. Methods of protein structure comparison. Methods Mol. Biol. 857, 231-257 (2012).

Scope & Limitations

RMSD is a global metric — misses local changes RMSD plateau can occur at unfolded state Multi-domain proteins have misleading RMSD