Improving the packing and accuracy of NMR structures with a pseudopotential for the radius of gyration
Improving the packing and accuracy of NMR structures with a pseudopotential for the radius of gyration
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DOI：
10.1021/ja9843730
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发表时间：
1999-03-17
影响因子：
15
通讯作者：
Clore, GM
中科院分区：
文献类型：
--
作者：
Kuszewski, J;Gronenborn, AM;Clore, GM
相对于X-射线结构，核磁共振结构往往填充较差，并有一定程度的膨胀。1这并不是溶液和晶体状态之间的差异的反映，而是实验数据和用于确定溶液核磁共振结构的计算方法的性质的反映。事实上，实验的核磁共振观测数据与根据高分辨率晶体结构计算的结果比根据相应的核磁共振结构计算的结果更符合。2核磁共振结构主要基于NOE衍生的短质子间距离限制，通常被归类为射程。NOE限制决定了蛋白质的折叠，并将各种结构元素拉入紧密的空间接近，但用于防止原子重叠的范德华项产生的排斥力往往会扩大结构。由于与NOE数据兼容的扩展结构可能比紧密堆积的结构多得多，因此可以将这种扩展视为一种熵效应。对于球状蛋白质来说，如果结构受到NOE数据的相对较好的限制，那么对于有许多相关的NOE距离限制和结构元件之间的距离受共价几何限制的球状蛋白质来说，膨胀的问题可能不会太严重。另一方面，由于分子间NOE的密度通常是有限的，并且分子间没有共价约束，分子间的界面将特别扩大。因此，需要一种能够抵消扩张趋势的结构性约束。在本文中，我们证明了引入旋转半径的赝势Rgyr，一个提供分子全局构象信息的参数，可以很容易地被纳入到核磁共振结构计算中，并导致精度的显著提高，特别是对于蛋白质-蛋白质复合体。一组原子的Rgyr定义为分子中每个原子到其质心的均方根距离，其中ri和Rj是原子i和j的位置向量，N是原子数。以前的工作表明，根据球状蛋白质或蛋白质结构域中的残基数量，可以使用关系Rgyr(Pred)2.2N残基0.38以合理的精度预测RgyR的值。3Rgyr也可以用小角X射线散射进行实验测量，其观测值与晶体结构计算值之间有很好的一致性。4Rgyr不是几何上特定的量。因此，将蛋白质结构限制在特定的Rgyr目标值并不限制它具有任何特定的结构，而是确保该结构总体上与大多数由X射线结晶学确定其结构的蛋白质一样紧密堆积。
NMR structures tend to be poorly packed and somewhat expanded relative to X-ray structures. 1 This is not a reflection of differences between the solution and crystal states, but rather of the nature of the experimental data and the computational methods employed to determine solution NMR structures. Indeed, the experimental NMR observables agree better with those calculated from high-resolution crystal structures than those calculated from the corresponding NMR structures. 2 NMR structures are mainly based on NOE-derived short interproton distance restraints which are generally classified into ranges. The NOE restraints determine the protein fold and pull the various structural elements into close spatial proximity, but the repulsive forces generated by the van der Waals term used to prevent atomic overlap tend to expand the structure. Because there are many more possible expanded structures than tightly packed ones that are compatible with the NOE data, the expansion can be regarded as an entropic effect. For globular proteins where there are numerous correlated NOE distance restraints and where the distance between structural elements is limited by covalent geometry, the problem of expansion may not be too severe, providing the structure is relatively well restrained by the NOE data. Intermolecular interfaces, on the other hand, will be particularly expanded since the density of intermolecular NOEs is usually limited and there are no intermolecular covalent restraints. Thus, there is a need for a structural restraint that can counteract the tendency toward expansion. In this paper, we demonstrate that the incorporation of a pseudopotential for the radius of gyration, Rgyr, a parameter that provides information regarding the global conformation of a molecule, can readily be incorporated into NMR structure calculations and results in significant increases in accuracy, particularly for protein-protein complexes. The Rgyr of a group of atoms is defined as the rms distance from each atom of the molecule to their centroid where ri and rj are the position vectors of atoms i and j, and N is the number of atoms. Previous work has shown that the value of Rgyr can be predicted with reasonable accuracy on the basis of the number of residues in a globular protein or protein domain using the relationship Rgyr (pred)) 2.2Nresidues 0.38. 3 Rgyr can also be measured experimentally using small-angle X-ray scattering with excellent agreement between observed values and those calculated from crystal structures. 4Rgyr is not a geometrically specific quantity. Thus, restraining a protein structure to a particular target value of Rgyr does not constrain it to have any specific structure, but ensures that the structure is overall about as tightly packed as the majority of proteins whose structures have been determined by X-ray crystallography.