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Published on: February 11, 2019
A method for efficient calculation of thermal stability of proteins upon point mutations
1Shanghai Engineering Research Center of Molecular Therapeutics & New Drug Development, Shanghai Key Laboratory of Green Chemistry & Chemical Process, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, China.
Abstract:
A method for efficient prediction of the relative stability of a protein due to a single amino acid point mutation is presented. In this approach, we calculate the free energy change due to an arbitrary point mutation of a protein from a single MD trajectory of the wild type protein. The method is tested on 27 diverse protein systems with a total of 853 mutations and the calculated relative free energies show a generally good correlation with the experimental values (a correlation coefficient of 0.63). Comparison with the free energy perturbation (FEP) method and the recently developed machine learning methods on two different benchmark data sets shows that the current method is computationally efficient and also numerically reliable for predicting the changes in thermostability upon an arbitrary point mutation of a protein. A discussion is provided on how to further improve the accuracy of the method for the prediction of thermostability of proteins.
