Li Da-Wei, Brüschweiler Rafael
Chemical Sciences Laboratory, Department of Chemistry and Biochemistry, and National High Magnetic Field Laboratory, Florida State University, Tallahassee, Florida, USA.
Biophys J. 2009 Apr 22;96(8):3074-81. doi: 10.1016/j.bpj.2009.01.011.
An all-atom local contact model is described that can be used to predict protein motions underlying isotropic crystallographic B-factors. It uses a mean-field approximation to represent the motion of an atom in a harmonic potential generated by the surrounding atoms resting at their equilibrium positions. Based on a 400-ns molecular dynamics simulation of ubiquitin in explicit water, it is found that each surrounding atom stiffens the spring constant by a term that on average scales exponentially with the interatomic distance. This model combines features of the local density model by Halle and the local contact model by Zhang and Brüschweiler. When applied to a nonredundant set of 98 ultra-high resolution protein structures, an average correlation coefficient of 0.75 is obtained for all atoms. The systematic inclusion of crystal contact contributions and fraying effects is found to enhance the performance substantially. Because the computational cost of the local contact model scales linearly with the number of protein atoms, it is applicable to proteins of any size for the prediction of B-factors of both backbone and side-chain atoms. The model performs as well as or better than several other models tested, such as rigid-body motional models, the local density model, and various forms of the elastic network model. It is concluded that at the currently achievable level of accuracy, collective intramolecular motions are not essential for the interpretation of B-factors.
本文描述了一种全原子局部接触模型，该模型可用于预测各向同性晶体学B因子背后的蛋白质运动。它使用平均场近似来表示原子在由处于平衡位置的周围原子产生的谐振势中的运动。基于泛素在显式水中的400纳秒分子动力学模拟，发现每个周围原子通过一个平均随原子间距离呈指数缩放的项来增强弹簧常数。该模型结合了哈勒的局部密度模型和张及布鲁施魏勒的局部接触模型的特点。当应用于98个超高分辨率蛋白质结构的非冗余集时，所有原子的平均相关系数为0.75。发现系统地纳入晶体接触贡献和磨损效应可显著提高性能。由于局部接触模型的计算成本与蛋白质原子数呈线性缩放，因此它适用于任何大小的蛋白质，用于预测主链和侧链原子的B因子。该模型的性能与其他几种测试模型相当或更好，如刚体运动模型、局部密度模型和各种形式的弹性网络模型。得出的结论是，在目前可达到的精度水平下，集体分子内运动对于B因子的解释并非必不可少。
