Universal Stability Model for Globular Proteins

Boris Fačkovec and Jiří Vondrášek

 

Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, v. v. i., Flemingovo nám. 2, 166 10 Praha, Czech Republic

 

Amino acid substitution is the common approach to engineer stability and function of globular proteins. Stability prediction of protein mutants and decoys from their 3D structures requires universal and

reliable energy function. Currently used functions for globular proteins are predominantly based on statistical force fields or on physics-based force fields lacking electrostatic interactions whose contribution vastly depends on the environment and solvation of the denatured state and is therefore very difficult to be estimated solely from the native structure. Here we propose a simple model of globular protein stability based on all-atom force field calculations integrating all types of stability contributions. From the derived energy functions we are going to develop fast and reliable automatic online predictor of stability change upon mutagenesis from native structure.