On the dissection of the unfolding reaction by the dissolution thermodynamics of N-alkyl amides.
Dissection of the unfolding thermodynamics based on small molecule dissolution led to controversial interpretations. It is proposed here that uncertainty about water transfer processes to be used in first approximation analyses of protein stability may be removed (i) separating liquid-dissolution-like effects from solid-like packing contributions; (ii) taking into account both peptide and side chain dissolution; and (iii) analysing the water-dependent part of the denaturation reaction by the dissolution thermodynamics of liquid N-alkyl amides. Based on these criteria, this paper analyses the entropy of the aqueous transfer of liquid N-alkyl amides filling a gap in a recent model of the unfolding energetics, which was limited to the enthalpy. Both enthalpic and entropic changes accompanying the liquid-dissolution-like immersion of internal amino acid residues in water during unfolding may be unambiguously described within this context. Although the model developed does not deepen our knowledge of protein unfolding, it may be of help in the analysis of whether liquid-dissolution-like effects or solid-like packing contributions play the major role in determining protein stability at elevated temperatures.
Ragone
Raffaele
R
Department of Biochemistry and Biophysics and CRISCEB, Second University of Naples, via Costantinopoli 16, 80138, Naples, Italy. ragone@unina2.it
D000577:Amides / Q000737:chemistry*; D019277:Entropy; D015233:Models, Statistical; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry*; D013696:Temperature; D013816:Thermodynamics
D000577:Amides; D011506:Proteins