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Biotechnology Journal

Publication date: 2011-06
Pages: 674 - 85
ISSN: 1860-6768, 1860-7314 PMID: 21538897
DOI: 10.1002/biot.201000331
Publisher: Wiley-VCH


Castillo Cano, Virginia
Graña-Montes, Ricardo ; Sabate, Raimon ; Ventura, Salvador


Algorithms, Amino Acid Sequence, Amyloid, Databases, Protein, Models, Chemical, Protein Binding, Protein Folding, Protein Structure, Secondary, Proteins, Proteome, Software, Biotechnology, 1002 Environmental Biotechnology, 1003 Industrial Biotechnology, 1004 Medical Biotechnology


In the cell, protein folding into stable globular conformations is in competition with aggregation into non-functional and usually toxic structures, since the biophysical properties that promote folding also tend to favor intermolecular contacts, leading to the formation of β-sheet-enriched insoluble assemblies. The formation of protein deposits is linked to at least 20 different human disorders, ranging from dementia to diabetes. Furthermore, protein deposition inside cells represents a major obstacle for the biotechnological production of polypeptides. Importantly, the aggregation behavior of polypeptides appears to be strongly influenced by the intrinsic properties encoded in their sequences and specifically by the presence of selective short regions with high aggregation propensity. This allows computational methods to be used to analyze the aggregation properties of proteins without the previous requirement for structural information. Applications range from the identification of individual amyloidogenic regions in disease-linked polypeptides to the analysis of the aggregation properties of complete proteomes. Herein, we review these theoretical approaches and illustrate how they have become important and useful tools in understanding the molecular mechanisms underlying protein aggregation.