Wells Stephen, Menor Scott, Hespenheide Brandon, Thorpe M F
Department of Physics and Astronomy, Arizona State University, Tempe, AZ 85287-1504, USA.
Phys Biol. 2005 Nov 9;2(4):S127-36. doi: 10.1088/1478-3975/2/4/S07.
We describe a new computational method, FRODA (framework rigidity optimized dynamic algorithm), for exploring the internal mobility of proteins. The rigid regions in the protein are first determined, and then replaced by ghost templates which are used to guide the movements of the atoms in the protein. Using random moves, the available conformational phase space of a 100 residue protein can be well explored in approximately 10-100 min of computer time using a single processor. All of the covalent, hydrophobic and hydrogen bond constraints are maintained, and van der Waals overlaps are avoided, throughout the simulation. We illustrate the results of a FRODA simulation on barnase, and show that good agreement is obtained with nuclear magnetic resonance experiments. We additionally show how FRODA can be used to find a pathway from one conformation to another. This directed dynamics is illustrated with the protein dihydrofolate reductase.
我们描述了一种用于探索蛋白质内部流动性的新计算方法——FRODA（框架刚性优化动态算法）。首先确定蛋白质中的刚性区域，然后用虚拟模板替换这些区域，虚拟模板用于引导蛋白质中原子的运动。通过随机移动，使用单个处理器在大约10 - 100分钟的计算机时间内可以很好地探索一个100个残基的蛋白质的可用构象相空间。在整个模拟过程中，所有共价键、疏水键和氢键约束都得以维持，并且避免了范德华重叠。我们展示了FRODA对核糖核酸酶 barnase 的模拟结果，并表明与核磁共振实验结果吻合良好。我们还展示了FRODA如何用于找到从一种构象到另一种构象的途径。这种定向动力学通过蛋白质二氢叶酸还原酶进行了说明。
