Exploring protein structural ensembles: Integration of sparse experimental data from electron paramagnetic resonance spectroscopy with molecular modeling methods
- Institute for Drug Discovery, Leipzig University Medical School, Germany
- Institute for Medical Physics and Biophysics, Leipzig University Medical School, Germany
- Integrative Center for Bioinformatics, Leipzig University, Germany
Figures
Figure 1
The conformational landscape of proteins.
Figure 2
Computational approaches for the analysis and interpretations of continuous wave (CW) electron paramagnetic resonance (EPR) data.
(A) Semi-empirical analysis of the CW EPR lineshape provides insight into the rate of motion (δ), polarity (A’zz) of the spin label environment, parallel (A॥), and perpendicular (A⊥) compounds of CW …
Figure 3
Computational methods for double electron–electron resonance (DEER) data analysis and integration.
(A, B) Combining approaches simultaneously model the dynamics of both a protein and spin labels. Full-atom and dummy representations of spin labels are possible. (C, D) Discriminating approaches …
Tables
Table 1
Summarizing information on electron paramagnetic resonance (EPR) spectroscopic techniques.
| Method | Features | References | |||
|---|---|---|---|---|---|
| Dynamics (timescale) | Structure(resolution) | Population | Computational analysis | ||
| CW EPR | Yes (10−10 to 10−7s) | Yes, via scanning (topology) | Yes, ≤3 conformations | Semi-empirical and lineshape analysis | Marsh, 1981; Hubbell and Altenbach, 1994; Columbus and Hubbell, 2002 |
| ST EPR | Yes (10−7 to 10−3 s) | No | No | Heuristic analysis | Hyde and Dalton, 1972 |
| TR EPR | Yes (>10−3 s) | No | Yes | Lineshape analysis | Farahbakhsh et al., 1993 |
| DEER | No | Yes (<10−10 m) | Yes | Parametric and non-parametric fitting models | Jeschke, 2012 |
| ENDOR | No | Yes (>10−11 m) | Yes | Lineshape analysis | Lubitz et al., 2002 |
| SR EPR | Yes, (10−6 to 10−5 s) | No | Yes, ≤2 conformations | Exponential fitting | Bridges et al., 2010 |
