Decoding Protein Stabilization: Impact on Aggregation, Solubility, and Unfolding Mechanisms.

ABSTRACT: Modern computational tools can predict the mutational effects on protein stability, sometimes at the expense of activity or solubility. Here, we investigate two homologous computationally stabilized haloalkane dehalogenases: (i) the soluble thermostable DhaA115 (T_m^app = 74 °C) and (ii) the poorly soluble and aggregating thermostable LinB116 (T_m^app = 65 °C), together with their respective wild-type variants. The intriguing difference in the solubility of these highly homologous proteins has remained unexplained for three decades. We combined experimental and in-silico techniques and examined the effects of stabilization on solubility and aggregation propensity. A detailed analysis of the unfolding mechanisms in the context of aggrega

SUBMITTER: Havlasek M 

PROVIDER: S-EPMC12381856 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature