Conformational dynamics of Ribonuclease Sa and its S48P mutant: Implications for the stability of the mutant protein

The optimization of β-turns has been used as a strategy to increase protein thermal stability. One example is the S48P mutation in Ribonuclease Sa, introduced to optimize a β-turn, which increases the stability of the protein as determined experimentally. Here, we have studied ⁴⁸SYGY⁵¹ β-turn and its S48P mutant from RNase Sa, as a peptide and as part of the protein, using molecular dynamics simulations. The turn propensity of the region ⁴⁸SYGY⁵¹ shows an increase in both the peptide and protein models on S48P mutation. The mutant protein shows an overall decrease in conformational dynamics and a decrease in conformational heterogeneity as compared to the wildtype protein. A comparatively restricted sampling of the φ-ψ region of GLN47, a pre PRO48 residue, in the mutant protein and some local changes in hydrogen bonding patterns involving residues 20-24 might be contributing to the mutant protein stability. In addition, some long-range hydrogen bonding interactions involving the 60s loop and the salt-bridge interaction involving ASP17-ARG63 could also be contributing to the increase in rigidity and stability of the mutant protein.