Masica David L, Gray Jeffrey J
Program in Molecular Biophysics, The Johns Hopkins University, Baltimore, Maryland 21218, USA.
Biophys J. 2009 Apr 22;96(8):3082-91. doi: 10.1016/j.bpj.2009.01.033.
We have developed a multiscale structure prediction technique to study solution- and adsorbed-state ensembles of biomineralization proteins. The algorithm employs a Metropolis Monte Carlo-plus-minimization strategy that varies all torsional and rigid-body protein degrees of freedom. We applied the technique to fold statherin, starting from a fully extended peptide chain in solution, in the presence of hydroxyapatite (HAp) (001), (010), and (100) monoclinic crystals. Blind (unbiased) predictions capture experimentally observed macroscopic and high-resolution structural features and show minimal statherin structural change upon adsorption. The dominant structural difference between solution and adsorbed states is an experimentally observed folding event in statherin's helical binding domain. Whereas predicted statherin conformers vary slightly at three different HAp crystal faces, geometric and chemical similarities of the surfaces allow structurally promiscuous binding. Finally, we compare blind predictions with those obtained from simulation biased to satisfy all previously published solid-state NMR (ssNMR) distance and angle measurements (acquired from HAp-adsorbed statherin). Atomic clashes in these structures suggest a plausible, alternative interpretation of some ssNMR measurements as intermolecular rather than intramolecular. This work demonstrates that a combination of ssNMR and structure prediction could effectively determine high-resolution protein structures at biomineral interfaces.
我们开发了一种多尺度结构预测技术,用于研究生物矿化蛋白的溶液态和吸附态集合。该算法采用了一种Metropolis蒙特卡罗加最小化策略,该策略可以改变蛋白质的所有扭转和刚体自由度。我们将该技术应用于折叠组蛋白,从溶液中完全伸展的肽链开始,在存在羟基磷灰石(HAp)(001)、(010)和(100)单斜晶体的情况下。盲法(无偏)预测捕捉到了实验观察到的宏观和高分辨率结构特征,并显示组蛋白在吸附时结构变化最小。溶液态和吸附态之间的主要结构差异是在组蛋白螺旋结合域中实验观察到的折叠事件。虽然预测的组蛋白构象在三个不同的HAp晶面上略有不同,但表面的几何和化学相似性允许结构上的混杂结合。最后,我们将盲法预测与通过偏向于满足所有先前发表的固态核磁共振(ssNMR)距离和角度测量(从HAp吸附的组蛋白获得)的模拟得到的预测进行比较。这些结构中的原子冲突表明,对一些ssNMR测量结果有一个合理的、替代的解释,即分子间而非分子内的解释。这项工作表明ssNMR和结构预测相结合可以有效地确定生物矿化界面处的高分辨率蛋白质结构。