Computational studies on mutant protein stability: The correlation between surface thermal expansion and protein stability.
Thermal stability of mutant proteins has been investigated using temperature dependent molecular dynamics (MD) simulations in vacuo. The numerical modeling was aimed at mimicking protein expansion upon heating. After the conditions for an expanding protein accessible surface area were established for T4 lysozyme and barnase wild-type proteins, MD simulations were carried out under the same conditions using the crystal structures of several mutant proteins. The computed thermal expansion of the accessible surface area of mutant proteins was found to be strongly correlated with their experimentally measured stabilities. A similar, albeit weaker, correlation was observed for model mutant proteins. This opens the possibility of obtaining stability information directly from protein structure.
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School of Physics, University of New South Wales, Sydney, Australia.
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D001426:Bacterial Proteins; D017122:Bacteriophage T4 / Q000737:chemistry; D003198:Computer Simulation; D007700:Kinetics; D008956:Models, Chemical; D009113:Muramidase / Q000737:chemistry; D016296:Mutagenesis; D011485:Protein Binding; D011487:Protein Conformation; D012260:Ribonucleases / Q000737:chemistry; D013696:Temperature; D013816:Thermodynamics
D001426:Bacterial Proteins; D012260:Ribonucleases; C019760:Bacillus amyloliquefaciens ribonuclease; D009113:Muramidase