The relationship between protein sequence and its thermodynamic stability is a critical aspect of computational protein design. In this work, we present a new theoretical method to calculate the free energy change (ΔΔG) resulting from a single-point amino acid mutation to alanine in a protein sequence. The method is derived based on physical interactions and is very efficient in estimating the free energy changes caused by a series of alanine mutations from just a single molecular dynamics (MD) trajectory. Numerical calculations are carried out on a total of 547 alanine mutations in 19 diverse proteins whose experimental results are available. The comparison between the experimental ΔΔGexp and the calculated values shows a generally good correlation with a correlation coefficient of 0.67. Both the advantages and limitations of this method are discussed. This method provides an efficient and valuable tool for protein design and engineering.
ASJC Scopus subject areas
- General Physics and Astronomy
- Physical and Theoretical Chemistry