Charge and Hydrophobicity Patterning along the Sequence Predicts the Folding Mechanism and Aggregation of Proteins:A Computational Approach

摘要

The presence of partially folded intermediates along the folding funnel of proteins has been suggested to be a signature of potentially aggregating systems.Many studies have concluded that metastable,highly flexible intermediates are the basic elements of the aggregation process.In a previous paper,we demonstrated how the choice between aggregation and folding behavior was influenced by hydrophobicity distribution patterning along the sequence,as quantified by recurrence quantification analysis(RQA)of the Myiazawa-Jernigan coded primary structures.In the present paper,we tried to unify the"partially folded intermediate"and"hydrophobicity/charge"models of protein aggregation verifying the ability of an empirical relation,developed for rationalizing the effect of different mutations on aggregation propensity of acyl-phosphatase and based on the combination of hydrophobicity RQA and charge descriptors,to discriminate in a statistically significant way two different protein populations:(a)proteins that fold by a process passing by partially folded intermediates and(b)proteins that do not present partially folded intermediates.