Charge and hydrophobicity patterning along the sequence predicts the folding mechanism and aggregation of proteins: a computational approach.
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.
Zbilut
Joseph P
JP
Department of Molecular Biophysics and Physiology, Rush Medical College, Chicago, IL 60612, USA.
Giuliani
Alessandro
A
Colosimo
Alfredo
A
Mitchell
Julie C
JC
Colafranceschi
Mauro
M
Marwan
Norbert
N
Webber
Charles L
CL
Uversky
Vladimir N
VN
D017766:Acid Anhydride Hydrolases / Q000737:chemistry*; D000595:Amino Acid Sequence; D019281:Dimerization; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D009154:Mutation; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry; D055672:Static Electricity; D000097024:Acylphosphatase
D017766:Acid Anhydride Hydrolases; D011506:Proteins; D000097024:Acylphosphatase