Spectral analysis of molecular dynamics simulations on PDZ: MD sectors
| Autor: | Bharat Lakhani, David L. Beveridge, Kelly M. Thayer, Emily Black |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Physics
0303 health sciences Sequence Spectrum Analysis 030303 biophysics PDZ domain PDZ Domains General Medicine Covariance Molecular Dynamics Simulation Article 03 medical and health sciences Molecular dynamics Prediction algorithms Protein stability Structural Biology Statistical coupling analysis Anisotropy Thermodynamics Spectral analysis Statistical physics Molecular Biology Algorithms |
| Zdroj: | J Biomol Struct Dyn |
| ISSN: | 1538-0254 |
| Popis: | Protein “sectors” is a theoretical construct positing that sparse subsets of amino acid residues form cooperative networks that are key elements of protein stability, ligand binding, and allosterism. Sectors in have been obtained for a number of proteins by Statistical Coupling Analysis (SCA) method of Ranganathan and co-workers, which involves the spectral analysis of conservation-weighted evolutionary covariance matrices obtained from a multiple sequence alignments of homologous families of proteins. SCA sectors have been successfully indentified with functional properties and allosterism in particular for a number of protein families. Here we investigate the utility of the sector idea for the analysis of physics-based molecular dynamics (MD) trajectories on proteins. The test case for this project is PSD95- PDZ3, a protein well characterized by x-ray crystallography, NMR spectroscopy and site specific mutagenisis, and one of the smallest systems for which allosterism has been experimentally observed. All-atom MD simulations were performed for a total of 500 nanoseconds. MD-calculated covariance matrices for the fluctuations of residue displacements and non-bonded interaction energies were subjected to spectral analysis in a manner analogous to that used to analyze positional correlation matrices in SCA. The composition of MD sectors was compared with results on SCA sectors and site specific mutagenesis. The agreement indicates that MD sectors to be a useful paradigm for analyzing protein MD trajectories, and likewise accounts for single domain allosterism in PDZ3. MD sectors are expected to be useful in the development of experimentally testable hypotheses on cooperativity, ligand binding, allosterism, and allosteric drug design. |
| Databáze: | OpenAIRE |
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