Possible Explanation of Destabilization of Asn to Ala Mutants

possible reasons  explanation  effect on mutant  support observed destab. of mutant?
residue conformational entropy Ala in bigger hole: more freedom motion, favored entropically stabilize mutant opposite observed. 

free energy excess cavity formation

energy penalty to make an unoccupied cavity

approx.  0. 8 kcal/mol



support observed but not size of observed effect (2.9 kcal/mol

free energy change for protein conformational changes rearrange protein to fill cavity stabilize mutant opposite observed