Holm L, Sander C
European Molecular Biology Laboratory, Heidelberg, Germany.
J Mol Biol. 1992 May 5;225(1):93-105. doi: 10.1016/0022-2836(92)91028-n.
Important properties of globular proteins, such as the stability of the folded state, depend sensitively on interactions with solvent molecules. An excluded volume approximation to protein-solvent interaction, the solvent contact model, was used to derive atomic solvation preference parameters from a database of known protein structures. The ability of solvation preference to discriminate between correct and incorrect three-dimensional structures for a given sequence, or to identify the correct sequence placement in a given structure, was tested. Backbone co-ordinates were taken from experimentally known structures or hypothetical models and side-chain conformations (in rotamer space) were optimized by an efficient Monte Carlo algorithm using simulated annealing and simple potential functions. Discrimination by solvation preference was very clear between deliberately misfolded and correct globular models as well as between native-like and non-native-like topologies of combinatorially generated myoglobin models. Due to its statistical nature, the evaluation works best on entire protein models, while the identification of incorrect parts of models is more difficult. In one case locally incorrect chain tracing in a crystal structure was identified. The method is computationally fast compared to methods based on surface area calculations and is recommended for use as a diagnostic tool in model building based on sequence similarity, in folding simulations and in protein design.
球状蛋白质的重要特性，如折叠态的稳定性，敏感地依赖于与溶剂分子的相互作用。一种蛋白质 - 溶剂相互作用的排斥体积近似法，即溶剂接触模型，被用于从已知蛋白质结构数据库中推导原子溶剂化偏好参数。测试了溶剂化偏好对于区分给定序列的正确和错误三维结构，或在给定结构中识别正确序列位置的能力。主链坐标取自实验已知结构或假设模型，侧链构象（在旋转异构体空间中）通过使用模拟退火和简单势函数的高效蒙特卡罗算法进行优化。在故意错误折叠的和正确的球状模型之间，以及在组合生成的肌红蛋白模型的天然样和非天然样拓扑结构之间，溶剂化偏好的区分非常明显。由于其统计性质，该评估在整个蛋白质模型上效果最佳，而识别模型的错误部分则更加困难。在一个案例中，识别出了晶体结构中局部错误的链追踪。与基于表面积计算的方法相比，该方法计算速度快，建议用作基于序列相似性的模型构建、折叠模拟和蛋白质设计中的诊断工具。
