Dispersive interactions govern strong thermal stability of a protein
| Authors | |
|---|---|
| Year of publication | 2007 |
| Type | Article in Periodical |
| Magazine / Source | Chemistry- A European Journal |
| MU Faculty or unit | |
| Citation | |
| Web | http://www3.interscience.wiley.com/cgi-bin/fulltext/114804131/HTMLSTART |
| Field | Biophysics |
| Keywords | ab initio calculations; hydrophobic core; hydrophobic effect; molecular modeling; NMR spectroscopy |
| Description | Rubredoxin from the hyperthermophile Pyrococcus furiosus (Pf Rd) is an extremely thermostable protein, which makes it an attractive subject of protein folding and stability studies. A fundamental question arises of what the reason for such extreme stability is and how it can be elucidated from a complex set of inter-atomic interactions. We addressed this issue first theoretically through a computational analysis of the hydrophobic core of the protein and its mutants including the interactions taking place inside the core. Here we show that a single mutation of one phenylalanine's residues inside the protein's hydrophobic core results in a dramatic decrease in its thermal stability. The calculated unfolding Gibbs energy as well as the stabilisation energy differences between a few core residues follow the same trend as the melting temperature of protein variants determined experimentally by microcalorimetry measurements. NMR experiments have shown that the only part of the protein affected by mutation is the reasonably rearranged hydrophobic core. It is hence concluded that stabilisation energies, which are dominated by London dispersion, represent the main source of stability of this protein. |
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