Molecular theory of the helix–coil transition in polyamino acids. V. Explanation of the different conformational behavior of valine, isoleucine, and leucine in aqueous solution

Even though poly(L‐valine) and poly(L‐isoleucine) both contain residues that are branched at their β‐carbon atoms, they exhibit a different behavior of their Zimm‐Bragg helix‐growth parameter s in aqueous solution. This quantity increases with temperature for poly(L‐valine) but decreases for poly(L‐isoleucine). The origin of this behavioral difference was examined by computing theoretical values of s versus temperature from interatomic interaction energies, taking solvent (hydrophobic and hydrophilic) effects into account. The calculated s versus temperature curves for both homopolymers are consistent with the observed experimental behavior. The two homopolymers behave differently because of differences in the change in the number of hydration‐shell water molecules accompanying their helix–coil transitions. The larger isoleucine side chains are more crowded together in both the α‐helical and coil forms than are those of valine. Therefore, there is a smaller change in hydration of the isoleucine side chains compared to that of the valine side chains in the helix–coil transition. By analyzing the effects of hydration on the s versus temperature curves, it is possible to account also for the experimental curve for poly(L‐leucine), which exhibits an intermediate behavior between those for poly(L‐valine) and poly(L‐isoleucine).