Computational design of thermostabilizing D-amino acid substitutions.

ABSTRACT: Judicious incorporation of D-amino acids in engineered proteins confers many advantages such as preventing degradation by endogenous proteases and promoting novel structures and functions not accessible to homochiral polypeptides. Glycine to D-alanine substitutions at the carboxy termini can stabilize α-helices by reducing conformational entropy. Beyond alanine, we propose additional side chain effects on the degree of stabilization conferred by D-amino acid substitutions. A detailed, molecular understanding of backbone and side chain interactions is important for developing rational, broadly applicable strategies in using D-amino acids to increase protein thermostability. Insight from structural bioinformatics combined with computational protein design can successfully guide the selection

SUBMITTER: Rodriguez-Granillo A 

PROVIDER: S-EPMC3443866 | biostudies-literature | 2011 Nov

REPOSITORIES: biostudies-literature