A new generation of statistical potentials for proteins
A new generation of statistical potentials for proteins
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DOI：
10.1529/biophysj.105.079434
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发表时间：
2006-06-01
影响因子：
3.4
通讯作者：
Rooman, M
中科院分区：
文献类型：
--
作者：
Dehouck, Y;Gilis, D;Rooman, M
我们提出了一种新的和灵活的衍生方案的统计，数据库派生，潜力，它允许一个同时考虑到特定的序列和结构描述符之间的相关性。该方案导致蛋白质的总折叠自由能分解为低阶项的总和，从而提供了独立分析每个贡献并澄清其意义和重要性的可能性，以避免过度计算某些贡献，并更有效地处理有限大小的数据库。此外，这个推导方案似乎是相当普遍的，许多以前开发的潜力可以表示为我们的形式主义的特殊情况。我们使用这种形式主义作为一个框架，以产生不同的残基为基础的能量函数，其性能进行评估的基础上，他们的能力，区分真正的蛋白质诱饵模型。最佳潜力产生的几个耦合项的组合，测量残基类型，骨干扭转角，溶剂accessories，相对位置沿着序列，和残基间的距离之间的相关性。该电位优于所有测试的基于残基的电位，甚至几个基于原子的电位。因此，将其纳入旨在预测蛋白质结构和稳定性的算法中，应该会大大提高其性能。
We propose a novel and flexible derivation scheme of statistical, database-derived, potentials, which allows one to take simultaneously into account specific correlations between several sequence and structure descriptors. This scheme leads to the decomposition of the total folding free energy of a protein into a sum of lower order terms, thereby giving the possibility to analyze independently each contribution and clarify its significance and importance, to avoid overcounting certain contributions, and to deal more efficiently with the limited size of the database. In addition, this derivation scheme appears as quite general, for many previously developed potentials can be expressed as particular cases of our formalism. We use this formalism as a framework to generate different residue-based energy functions, whose performances are assessed on the basis of their ability to discriminate genuine proteins from decoy models. The optimal potential is generated as a combination of several coupling terms, measuring correlations between residue types, backbone torsion angles, solvent accessibilities, relative positions along the sequence, and interresidue distances. This potential outperforms all tested residue-based potentials, and even several atom-based potentials. Its incorporation in algorithms aiming at predicting protein structure and stability should therefore substantially improve their performances.