Molecular dynamics simulations of an engineered T4 lysozyme exclude helix to sheet transition, and provide insights into long distance, intra‐protein switchable motion
| Autor: | Mohammad S. Yousef, Edward Ackad, Laurence Biggers, Hadeer Elhabashy |
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| Rok vydání: | 2019 |
| Předmět: |
Physics
0303 health sciences Markov chain Protein Conformation 030302 biochemistry & molecular biology Dynamics (mechanics) Context (language use) Articles Protein engineering Molecular Dynamics Simulation Protein Engineering Biochemistry Folding (chemistry) Turn (biochemistry) 03 medical and health sciences Molecular dynamics Chemical physics Mutation Helix Bacteriophage T4 Muramidase Molecular Biology 030304 developmental biology |
| Zdroj: | Protein Sci |
| ISSN: | 1469-896X 0961-8368 |
| Popis: | An engineered variant of T4 lysozyme serves as a model for studying induced remote conformational changes in a full protein context. The design involves a duplicated surface helix, flanked by two loops, that switches between two different conformations spanning about 20 Å. Molecular dynamics simulations of the engineered protein, up to 1 μs, rule out α‐helix to β‐sheet transitions within the duplicated helix as suggested by others. These simulations highlight how the use of different force fields can lead to radical differences in the structure of the protein. In addition, Markov state modeling and transition path theory were employed to map a 6.6 μs simulation for possible early intermediate states and to provide insights into the onset of the switching motion. The putative intermediates involve the folding of one helical turn in the C‐terminal loop through energy driven, sequential rearrangement of nearby salt bridges around the key residue Arg63. These results provide a first step towards understanding the energetics and dynamics of a rather complicated intra‐protein motion. |
| Databáze: | OpenAIRE |
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