AGGRESCAN: a server for the prediction and evaluation of "hot spots" of aggregation in polypeptides.
AGGRESCAN: a server for the prediction and evaluation of "hot spots" of aggregation in polypeptides.
复制标题
DOI：
10.1186/1471-2105-8-65
复制
发表时间：
2007-02-27
影响因子：
3
通讯作者：
Ventura S
中科院分区：
文献类型：
--
作者：
Conchillo-Solé O;de Groot NS;Avilés FX;Vendrell J;Daura X;Ventura S
蛋白质聚集与几种发病率不断增长的衰弱性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，蛋白质生产往往受到重组蛋白聚集成聚集体的阻碍。因此，开发预测多肽聚集特性的方法正受到越来越多的关注。AGGRESCAN是一个基于网络的软件，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基于来自体内实验的天然氨基酸的聚集倾向量表，并假设短且特异性的序列延伸调节蛋白质聚集。该算法被证明，以确定一系列的蛋白质片段参与疾病相关蛋白质的聚集，并预测其沉积倾向的基因突变的影响。它还提供了新的见解，显示球状蛋白，天然未折叠的多肽，淀粉样蛋白和蛋白质中发现的细菌包涵体的差异聚集特性。通过鉴定蛋白质中易聚集的片段，AGGRESCAN将有助于（i）鉴定构象疾病中抗沉积策略的可能治疗靶点，以及（ii）预测生物活性多肽或多肽组储存或重组生产过程中的聚集现象。
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 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.
登录
查看更多内容
DOI：
10.1073/pnas.0303758100
发表时间：
2003-12-23
影响因子：
11.1
作者：
Fändrich, M;Forge, V;Diekmann, S
通讯作者：
Diekmann, S
DOI：
10.1073/pnas.212527999
发表时间：
2002-12-10
影响因子：
11.1
作者：
Chiti, F;Calamai, M;Dobson, CM
通讯作者：
Dobson, CM
DOI：
10.1073/pnas.96.7.3590
发表时间：
1999-03-30
影响因子：
11.1
作者：
Chiti, F;Webster, P;Dobson, CM
通讯作者：
Dobson, CM
影响因子：
2.9
作者：
Gamblin, TC;Berry, RW;Binder, LI
通讯作者：
Binder, LI
影响因子：
5.4
作者：
de Groot, NS;Aviles, FX;Ventura, S
通讯作者：
Ventura, S