Determination of Ensemble-Average Pairwise Root Mean-Square Deviation from Experimental B-Factors
| Autor: | Bojan Zagrovic, Antonija Kuzmanic |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Protein Folding
root-mean square deviation B-factors ensemble-average Protein Conformation Biophysics Crystallography X-Ray 010402 general chemistry 01 natural sciences Measure (mathematics) 03 medical and health sciences Molecular dynamics Computational chemistry Cluster (physics) Statistical physics Root-mean-square deviation 030304 developmental biology Quantitative Biology::Biomolecules 0303 health sciences Basis (linear algebra) Chemistry Protein Microfilament Proteins computer.file_format Protein Data Bank Protein Structure Tertiary 0104 chemical sciences Distribution (mathematics) Pairwise comparison computer |
| Zdroj: | Biophysical Journal. 98:861-871 |
| ISSN: | 0006-3495 |
| DOI: | 10.1016/j.bpj.2009.11.011 |
| Popis: | Root mean-square deviation (RMSD) after roto-translational least-squares fitting is a measure of global structural similarity of macromolecules used commonly. On the other hand, experimental x-ray B-factors are used frequently to study local structural heterogeneity and dynamics in macromolecules by providing direct information about root mean-square fluctuations (RMSF) that can also be calculated from molecular dynamics simulations. We provide a mathematical derivation showing that, given a set of conservative assumptions, a root mean-square ensemble-average of an all-against-all distribution of pairwise RMSD for a single molecular species, (1/2), is directly related to average B-factors (B) and (1/2). We show this relationship and explore its limits of validity on a heterogeneous ensemble of structures taken from molecular dynamics simulations of villin headpiece generated using distributed-computing techniques and the Folding@Home cluster. Our results provide a basis for quantifying global structural diversity of macromolecules in crystals directly from x-ray experiments, and we show this on a large set of structures taken from the Protein Data Bank. In particular, we show that the ensemble-average pairwise backbone RMSD for a microscopic ensemble underlying a typical protein x-ray structure is approximately 1.1 A, under the assumption that the principal contribution to experimental B-factors is conformational variability. |
| Databáze: | OpenAIRE |
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