Assessment of Four Theoretical Approaches to Predict Protein Flexibility in the Crystal Phase and Solution

• Published in: Journal of chemical theory and computation Vol. 20; no. 17; pp. 7667 - 7681
• Main Authors: Dziadek, Ł. J., Sieradzan, A. K., Czaplewski, C., Zalewski, M., Banaś, F., Toczek, M., Nisterenko, W., Grudinin, S., Liwo, A., Giełdoń, A.
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 10-09-2024
• Subjects: Biomolecular Systems; Cabs; Correlation coefficients; Crystallography; Crystallography, X-Ray; Models, Molecular; NMR spectroscopy; Nuclear Magnetic Resonance, Biomolecular; Polypeptides; Protein Conformation; Protein Structure, Secondary; Proteins; Proteins - chemistry; Rigid blocks; Solutions
• ISSN: 1549-9618; 1549-9626; 1549-9626
• DOI: 10.1021/acs.jctc.4c00754

In this paper, we evaluated the ability of four coarse-grained methods to predict protein flexible regions with potential biological importance, UNRES-flex, UNRES-DSSP-flex (based on the united residue model of polypeptide chains without and with secondary structure restraints, respectively), CABS-flex (based on the C-α, C-β, and side chain model), and nonlinear rigid block normal mode analysis (NOLB) with a set of 100 protein structures determined by NMR spectroscopy or X-ray crystallography, with all secondary structure types. End regions with high fluctuations were excluded from analysis. The Pearson and Spearman correlation coefficients were used to quantify the conformity between the calculated and experimental fluctuation profiles, the latter determined from NMR ensembles and X-ray B-factors, respectively. For X-ray structures (corresponding to proteins in a crowded environment), NOLB resulted in the best agreement between the predicted and experimental fluctuation profiles, while for NMR structures (corresponding to proteins in solution), the ranking of performance is CABS-flex > UNRES-DSSP-flex > UNRES-flex > NOLB; however, CABS-flex sometimes exaggerated the extent of small fluctuations, as opposed to UNRES-DSSP-flex.