BCL::Fold - De Novo Prediction of Complex and Large Protein Topologies by Assembly of Secondary Structure Elements
BCL::Fold - De Novo Prediction of Complex and Large Protein Topologies by Assembly of Secondary Structure Elements
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DOI：
10.1371/journal.pone.0049240
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发表时间：
2012-11-16
期刊：
影响因子：
3.7
通讯作者：
Meiler, Jens
中科院分区：
文献类型：
--
作者：
Karakas, Mert;Woetzel, Nils;Meiler, Jens
计算从头蛋白质结构预测仅限于简单拓扑结构的小蛋白质。目前的工作探索了一种方法，通过组装蛋白质拓扑结构从理想化的α-螺旋和β-链，以超越目前的限制。该算法进行了蒙特卡洛大都会模拟退火折叠模拟。它优化了基于知识的潜力，分析回转半径，β链配对，二级结构元件（SSE）包装，氨基酸对距离，氨基酸环境，接触顺序，二级结构预测一致性和环闭合。蛋白质链的中断有利于非局部接触的采样，从而产生复杂的蛋白质拓扑结构。通过排除柔性环区域进一步减小构象搜索空间的大小来加速折叠模拟。该算法以长度在83至293个氨基酸之间的66种蛋白质为基准。对于这些蛋白质中的61种，所获得的最佳仅SSE模型具有低于8.0埃的RMSD 100，并且恢复了超过20%的天然接触。该算法组装蛋白质拓扑结构与多达215个残基和相对接触顺序为0.46。该方法是定制的，以结合使用低分辨率或稀疏的实验数据集，这往往提供限制的区域定义的二级结构。
Computational de novo protein structure prediction is limited to small proteins of simple topology. The present work explores an approach to extend beyond the current limitations through assembling protein topologies from idealized alpha-helices and beta-strands. The algorithm performs a Monte Carlo Metropolis simulated annealing folding simulation. It optimizes a knowledge-based potential that analyzes radius of gyration, beta-strand pairing, secondary structure element (SSE) packing, amino acid pair distance, amino acid environment, contact order, secondary structure prediction agreement and loop closure. Discontinuation of the protein chain favors sampling of non-local contacts and thereby creation of complex protein topologies. The folding simulation is accelerated through exclusion of flexible loop regions further reducing the size of the conformational search space. The algorithm is benchmarked on 66 proteins with lengths between 83 and 293 amino acids. For 61 out of these proteins, the best SSE-only models obtained have an RMSD100 below 8.0 angstrom and recover more than 20% of the native contacts. The algorithm assembles protein topologies with up to 215 residues and a relative contact order of 0.46. The method is tailored to be used in conjunction with low-resolution or sparse experimental data sets which often provide restraints for regions of defined secondary structure.