Borguesan Bruno, Barbachan e Silva Mariel, Grisci Bruno, Inostroza-Ponta Mario, Dorn Márcio
Federal University of Rio Grande do Sul, Institute of Informatics, Av. Bento Gonçalves 9500, 91501-970 Porto Alegre, RS, Brazil.
Departamento de Ingeniería Informática, Center for Biotechnology and Bioengineering, Universidad de Santiago de Chile, Av. Ecuador 3659, Santiago, Chile.
Comput Biol Chem. 2015 Dec;59 Pt A:142-57. doi: 10.1016/j.compbiolchem.2015.08.006. Epub 2015 Sep 5.
Tertiary protein structure prediction is one of the most challenging problems in structural bioinformatics. Despite the advances in algorithm development and computational strategies, predicting the folded structure of a protein only from its amino acid sequence remains as an unsolved problem. We present a new computational approach to predict the native-like three-dimensional structure of proteins. Conformational preferences of amino acid residues and secondary structure information were obtained from protein templates stored in the Protein Data Bank and represented as an Angle Probability List. Two knowledge-based prediction methods based on Genetic Algorithms and Particle Swarm Optimization were developed using this information. The proposed method has been tested with twenty-six case studies selected to validate our approach with different classes of proteins and folding patterns. Stereochemical and structural analysis were performed for each predicted three-dimensional structure. Results achieved suggest that the Angle Probability List can improve the effectiveness of metaheuristics used to predicted the three-dimensional structure of protein molecules by reducing its conformational search space.
三级蛋白质结构预测是结构生物信息学中最具挑战性的问题之一。尽管在算法开发和计算策略方面取得了进展,但仅从氨基酸序列预测蛋白质的折叠结构仍然是一个未解决的问题。我们提出了一种新的计算方法来预测蛋白质的天然三维结构。氨基酸残基的构象偏好和二级结构信息从存储在蛋白质数据库中的蛋白质模板中获得,并表示为角度概率列表。利用这些信息开发了两种基于遗传算法和粒子群优化的基于知识的预测方法。该方法已通过26个案例研究进行了测试,这些案例研究旨在验证我们针对不同类型蛋白质和折叠模式的方法。对每个预测的三维结构进行了立体化学和结构分析。结果表明,角度概率列表可以通过减少其构象搜索空间来提高用于预测蛋白质分子三维结构的元启发式算法的有效性。