Extracting knowledge from protein structure geometry.
Extracting knowledge from protein structure geometry.
复制标题
从蛋白质结构几何中提取知识。
DOI：
10.1002/prot.24242
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发表时间：
2013
期刊：
影响因子：
2.9
通讯作者：
Koehl,Patrice
中科院分区：
文献类型：
--
作者：
Rogen,Peter;Koehl,Patrice
蛋白质结构预测技术分两步进行，即为感兴趣的蛋白质生成许多结构模型，然后评估所有这些模型以识别那些天然的。理论上，第二步很容易，因为天然结构对应于其自由能表面的最小值。然而，众所周知，情况更加复杂，因为目前用于分子模拟的力场无法从错误折叠的结构中识别出天然状态。在试图解决这个问题，我们遵循另一种方法，并从天然和错误折叠的蛋白质结构的构象提取的几何知识中获得一个新的潜力。这种新的潜力，公制蛋白质潜力（MPP），有两个主要特点是其成功的关键。首先，它是复合的，因为它包括蛋白质的局部和非局部几何信息。在短程水平上，它通过引入新的局部能量项来捕获和量化蛋白质骨架的短（7聚体）片段的序列和结构之间的映射。然后用非局部残基成对势和溶剂势来增强局部能量项。其次，它被优化以产生结构模型的能量与其相对于相应蛋白质的天然结构的均方根（RMS）之间的最大化相关性。我们已经证明，MPP在RMS和能量之间产生高相关值，并且它能够从一组高分辨率诱饵中检索蛋白质的天然结构。蛋白质2013。© 2012 Wiley Periodicals，Inc.
Protein structure prediction techniques proceed in two steps, namely the generation of many structural models for the protein of interest, followed by an evaluation of all these models to identify those that are native‐like. In theory, the second step is easy, as native structures correspond to minima of their free energy surfaces. It is well known however that the situation is more complicated as the current force fields used for molecular simulations fail to recognize native states from misfolded structures. In an attempt to solve this problem, we follow an alternate approach and derive a new potential from geometric knowledge extracted from native and misfolded conformers of protein structures. This new potential, Metric Protein Potential (MPP), has two main features that are key to its success. Firstly, it is composite in that it includes local and nonlocal geometric information on proteins. At the short range level, it captures and quantifies the mapping between the sequences and structures of short (7‐mer) fragments of protein backbones through the introduction of a new local energy term. The local energy term is then augmented with a nonlocal residue‐based pairwise potential, and a solvent potential. Secondly, it is optimized to yield a maximized correlation between the energy of a structural model and its root mean square (RMS) to the native structure of the corresponding protein. We have shown that MPP yields high correlation values between RMS and energy and that it is able to retrieve the native structure of a protein from a set of high‐resolution decoys. Proteins 2013. © 2012 Wiley Periodicals, Inc.