Dunbrack R L, Karplus M
Department of Chemistry, Harvard University, Cambridge, MA 02138.
J Mol Biol. 1993 Mar 20;230(2):543-74. doi: 10.1006/jmbi.1993.1170.
A backbone-dependent rotamer library for amino acid side-chains is developed and used for constructing protein side-chain conformations from the main-chain co-ordinates. The rotamer library is obtained from 132 protein chains in the Brookhaven Protein Database. A grid of 20 degrees by 20 degrees blocks for the main-chain angles phi, psi is used in the rotamer library. Significant correlations are found between side-chain dihedral angle probabilities and backbone phi, psi values. These probabilities are used to place the side-chains on the known backbone in test applications for six proteins for which high-resolution crystal structures are available. A minimization scheme is used to reorient side-chains that conflict with the backbone or other side-chains after the initial placement. The initial placement yields 59% of both chi 1 and chi 2 values in the correct position (to within 40 degrees) for thermolysin to 81% for crambin. After refinement the values range from 61% (lysozyme) to 89% (crambin). It is evident from the results that a single protein does not adequately test a prediction scheme. The computation time required by the method scales linearly with the number of side-chains. An initial prediction from the library takes only a few seconds of computer time, while the iterative refinement takes on the order of hours. The method is automated and can easily be applied to aid experimental side-chain determinations and homology modeling. The high degree of correlation between backbone and side-chain conformations may introduce a simplification in the protein folding process by reducing the available conformational space.
开发了一种基于主链的氨基酸侧链旋转异构体库，并用于根据主链坐标构建蛋白质侧链构象。该旋转异构体库取自布鲁克海文蛋白质数据库中的132条蛋白质链。在旋转异构体库中使用了一个由主链角度φ、ψ构成的20度×20度的网格。发现侧链二面角概率与主链φ、ψ值之间存在显著相关性。在六个有高分辨率晶体结构的蛋白质的测试应用中，这些概率被用于将侧链放置在已知的主链上。在初始放置后，使用一种最小化方案来重新定向与主链或其他侧链冲突的侧链。初始放置后，嗜热菌蛋白酶的χ1和χ2值在正确位置（误差在40度以内）的比例为59%，而胰凝乳蛋白酶原的这一比例为81%。经过优化后，该比例范围从61%（溶菌酶）到89%（胰凝乳蛋白酶原）。从结果可以明显看出，单一蛋白质不足以充分测试一种预测方案。该方法所需的计算时间与侧链数量呈线性关系。从库中进行的初始预测仅需几秒钟的计算机时间，而迭代优化则需要数小时。该方法是自动化的，可轻松应用于辅助实验性侧链确定和同源建模。主链和侧链构象之间的高度相关性可能通过减少可用的构象空间，在蛋白质折叠过程中引入一种简化。
