Mupain: Better binding with higher entropy

Mupain: Better binding with higher entropy

PDB entry:

The structure of a cyclic peptide, mupain, which acts as a protease inhibitor has been released this week, in several variants derived from a peptide library.

Because the peptide does not align properly with the active site residues, it is not cleaved and so acts as an inhibitor not a substrate.

An aspartate-to-alanine substitution resulted in increased binding affinity in spite of a less favorable binding entropy which the authors attribute to increased flexibility allowing more favorable interactions. 

The work is descibed by Zhao et al. in PLoS ONE. DOI: