Andrec Michael, Harano Yuichi, Jacobson Matthew P, Friesner Richard A, Levy Ronald M
Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, 610 Taylor Road, Piscataway, NJ 08854-8087, USA.
J Struct Funct Genomics. 2002;2(2):103-11. doi: 10.1023/a:1020435630054.
Residual dipolar couplings provide significant structural information for proteins in the solution state, which makes them attractive for the rapid determination of protein structures. While dipolar couplings contain inherent structural ambiguities, these can be reduced via an overlap similarity measure that insists that protein fragments assigned to overlapping regions of the sequence must have self-consistent structures. This allows us to determine a backbone fold (including the correct Calpha-Cbeta bond orientations) using only residual dipolar coupling data from one ordering medium. The resulting backbone structures are of sufficient quality to allow for modeling of sidechain rotamer states using a rotamer prediction algorithm and a force field employing the Surface Generalized Born continuum solvation model. We demonstrate the applicability of the method using experimental data for ubiquitin. These results illustrate the synergies that are possible between protein structural database and molecular modeling methods and NMR spectroscopy, and we expect that the further development of these methods will lead to the extraction of high resolution structural information from minimal NMR data.
残余偶极耦合为溶液状态下的蛋白质提供了重要的结构信息，这使得它们对于快速确定蛋白质结构具有吸引力。虽然偶极耦合存在固有的结构模糊性，但可以通过重叠相似性度量来减少这些模糊性，该度量要求分配到序列重叠区域的蛋白质片段必须具有自洽的结构。这使我们能够仅使用来自一种有序介质的残余偶极耦合数据来确定主链折叠（包括正确的Cα-Cβ键取向）。所得的主链结构质量足以使用旋转异构体预测算法和采用表面广义玻恩连续溶剂化模型的力场来模拟侧链旋转异构体状态。我们使用泛素的实验数据证明了该方法的适用性。这些结果说明了蛋白质结构数据库与分子建模方法以及核磁共振光谱之间可能存在的协同作用，并且我们预计这些方法的进一步发展将导致从最少的核磁共振数据中提取高分辨率结构信息。
