Conchillo-Solé Oscar, de Groot Natalia S, Avilés Francesc X, Vendrell Josep, Daura Xavier, Ventura Salvador
Institut de Biotecnologia i de Biomedicina (IBB), Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain.
BMC Bioinformatics. 2007 Feb 27;8:65. doi: 10.1186/1471-2105-8-65.
Protein aggregation correlates with the development of several debilitating human disorders of growing incidence, such as Alzheimer's and Parkinson's diseases. On the biotechnological side, protein production is often hampered by the accumulation of recombinant proteins into aggregates. Thus, the development of methods to anticipate the aggregation properties of polypeptides is receiving increasing attention. AGGRESCAN is a web-based software for the prediction of aggregation-prone segments in protein sequences, the analysis of the effect of mutations on protein aggregation propensities and the comparison of the aggregation properties of different proteins or protein sets.
AGGRESCAN is based on an aggregation-propensity scale for natural amino acids derived from in vivo experiments and on the assumption that short and specific sequence stretches modulate protein aggregation. The algorithm is shown to identify a series of protein fragments involved in the aggregation of disease-related proteins and to predict the effect of genetic mutations on their deposition propensities. It also provides new insights into the differential aggregation properties displayed by globular proteins, natively unfolded polypeptides, amyloidogenic proteins and proteins found in bacterial inclusion bodies.
By identifying aggregation-prone segments in proteins, AGGRESCAN http://bioinf.uab.es/aggrescan/ shall facilitate (i) the identification of possible therapeutic targets for anti-depositional strategies in conformational diseases and (ii) the anticipation of aggregation phenomena during storage or recombinant production of bioactive polypeptides or polypeptide sets.
蛋白质聚集与几种日益常见的使人衰弱的人类疾病的发展相关，如阿尔茨海默病和帕金森病。在生物技术方面，重组蛋白的积累常常阻碍蛋白质的生产。因此，开发预测多肽聚集特性的方法越来越受到关注。AGGRESCAN是一款基于网络的软件，用于预测蛋白质序列中易于聚集的片段、分析突变对蛋白质聚集倾向的影响以及比较不同蛋白质或蛋白质组的聚集特性。
AGGRESCAN基于从体内实验得出的天然氨基酸聚集倾向量表，并假设短的特定序列片段调节蛋白质聚集。该算法被证明能够识别一系列与疾病相关蛋白质聚集有关的蛋白质片段，并预测基因突变对其沉积倾向的影响。它还为球状蛋白、天然未折叠多肽、淀粉样蛋白和细菌包涵体中的蛋白质所显示的不同聚集特性提供了新的见解。
通过识别蛋白质中易于聚集的片段，AGGRESCAN（http://bioinf.uab.es/aggrescan/）将有助于：（i）确定构象疾病中抗沉积策略的可能治疗靶点；（ii）预测生物活性多肽或多肽组在储存或重组生产过程中的聚集现象。
