Experimental and Computational Analysis of Protein Stabilization by Gly-to-d-Ala Substitution: A Convolution of Native State and Unfolded State Effects.

ABSTRACT: The rational and predictable enhancement of protein stability is an important goal in protein design. Most efforts target the folded state, however stability is the free energy difference between the folded and unfolded states thus both are suitable targets. Strategies directed at the unfolded state usually seek to decrease chain entropy by introducing cross-links or by replacing glycines. Cross-linking has led to mixed results. Replacement of glycine with an l-amino acid, while reducing the entropy of the unfolded state, can introduce unfavorable steric interactions in the folded state, since glycine is often found in conformations that require a positive φ angle such as helical C-capping motifs or type I' and II″ β-turns. l-Amino acids are strongly disfavored in these conformations, but

SUBMITTER: Zou J 

PROVIDER: S-EPMC5442443 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature