Prediction of the maximal stability temperature of monomeric globular proteins solely from amino acid sequence

Abstract

Globular protein thermostability is characterized the cold denaturation, maximal stability (T_ms) and heat denaturation temperatures. For mesophilic globular proteins, T_ms typically ranges from −25°C to +35°C. We show that the indirect estimate of T_ms from calorimetry and the direct estimate from chemical denaturation performed in a range of temperatures are in close agreement. The heat capacity change of unfolding per mol residue (ΔC_p) alone is shown to accurately predict T_ms.ΔC_p and hence T_ms can be predicted solely from the protein sequence. The average difference in free energy of unfolding at the observed and predicted values of T_ms is 1.0 kcal mol⁻¹, which is small compared to typical values of the total free energy of unfolding.