Schlessinger Avner, Punta Marco, Rost Burkhard
Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY, USA.
Bioinformatics. 2007 Sep 15;23(18):2376-84. doi: 10.1093/bioinformatics/btm349. Epub 2007 Aug 20.
Natively unstructured (also dubbed intrinsically disordered) regions in proteins lack a defined 3D structure under physiological conditions and often adopt regular structures under particular conditions. Proteins with such regions are overly abundant in eukaryotes, they may increase functional complexity of organisms and they usually evade structure determination in the unbound form. Low propensity for the formation of internal residue contacts has been previously used to predict natively unstructured regions.
We combined PROFcon predictions for protein-specific contacts with a generic pairwise potential to predict unstructured regions. This novel method, Ucon, outperformed the best available methods in predicting proteins with long unstructured regions. Furthermore, Ucon correctly identified cases missed by other methods. By computing the difference between predictions based on specific contacts (approach introduced here) and those based on generic potentials (realized in other methods), we might identify unstructured regions that are involved in protein-protein binding. We discussed one example to illustrate this ambitious aim. Overall, Ucon added quality and an orthogonal aspect that may help in the experimental study of unstructured regions in network hubs.
http://www.predictprotein.org/submit_ucon.html.
Supplementary data are available at Bioinformatics online.
蛋白质中的天然非结构化（也称为内在无序）区域在生理条件下缺乏明确的三维结构，并且在特定条件下通常会形成规则结构。具有此类区域的蛋白质在真核生物中极为丰富，它们可能会增加生物体的功能复杂性，并且通常以未结合形式逃避结构测定。先前已利用内部残基接触形成的低倾向性来预测天然非结构化区域。
我们将针对蛋白质特异性接触的PROFcon预测与通用的成对势相结合，以预测非结构化区域。这种名为Ucon的新方法在预测具有长非结构化区域的蛋白质方面优于现有最佳方法。此外，Ucon正确识别出了其他方法遗漏的情况。通过计算基于特异性接触的预测（此处介绍的方法）与基于通用势的预测（其他方法中实现的）之间的差异，我们或许能够识别出参与蛋白质-蛋白质结合的非结构化区域。我们讨论了一个例子来说明这一宏大目标。总体而言，Ucon提高了质量并提供了一个正交方面，这可能有助于对网络枢纽中非结构化区域的实验研究。
http://www.predictprotein.org/submit_ucon.html。
补充数据可在《生物信息学》在线获取。
