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A Protocol for Computer-Based Protein Structure and Function Prediction
Published on: November 3, 2011
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BCL::MP-fold: Membrane protein structure prediction guided by EPR restraints
Axel W Fischer1,2, Nathan S Alexander1,2, Nils Woetzel1,2
1Department of Chemistry, Vanderbilt University, Nashville, Tennessee, 37232.
Proteins
|March 31, 2015
Summary
Determining membrane protein topology is challenging. This study shows Electron Paramagnetic Resonance (EPR) spectroscopy, combined with the BCL::MP-Fold algorithm, accurately predicts membrane protein structures using distance and accessibility data.
Area of Science:
- Biophysics
- Structural Biology
- Computational Biology
Background:
- Determining membrane protein topology is crucial but challenging for traditional methods like X-ray crystallography and NMR spectroscopy.
- Electron Paramagnetic Resonance (EPR) spectroscopy offers an alternative approach for studying membrane protein structure and dynamics.
Purpose of the Study:
- To demonstrate the feasibility of using limited EPR distance and accessibility measurements for membrane protein topology determination.
- To develop and validate an algorithm for assembling secondary structure elements (SSEs) in membrane proteins.
Main Methods:
- Utilized the BCL::MP-Fold (BioChemical Library membrane protein fold) algorithm, employing a Monte Carlo Metropolis (MCM) approach to assemble SSEs.
- Integrated knowledge-based potential functions and a knowledge-based energy function for model evaluation.
- Incorporated limited EPR distance and accessibility measurements to refine and validate predicted models.
Main Results:
- The BCL::MP-Fold algorithm successfully predicted the topology of 29 membrane proteins, with high accuracy (RMSD100 < 4 Å for 15 proteins).
- The algorithm demonstrated significant improvement in discriminating native topologies, with average enrichment increasing from 1.3 to 2.5.
- The study validated the utility of EPR data in enhancing the accuracy of computational protein structure prediction.
Conclusions:
- Limited EPR distance and accessibility measurements are effective for determining membrane protein topology.
- The BCL::MP-Fold algorithm, enhanced by EPR data, provides a powerful tool for predicting membrane protein structures.
- This approach advances the study of membrane protein structure and dynamics, overcoming limitations of conventional techniques.
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