Kuriyan J, Brünger A T, Karplus M, Hendrickson W A
Laboratory of Bioorganic Chemistry and Biochemistry, Rockefeller University, New York, NY 10021.
Acta Crystallogr A. 1989 Jun 1;45 ( Pt 6):396-409. doi: 10.1107/s0108767389000437.
The recently developed method of structure factor refinement by molecular dynamics with simulated annealing [Brünger, Kuriyan & Karplus (1987). Science, 235, 458-460] is tested on the 118 residue protein myohemerythrin. A highly refined structure for this protein at 1.3/1.7 A resolution has recently been published [Sheriff, Hendrickson & Smith (1987). J. Mol. Biol. 197, 273-296]. This is compared with the results of simulated annealing refinement (with no manual intervention) starting from an earlier model for the protein from a stage in the refinement when conventional least-squares methods could not improve the structure. Simulated annealing reduces the R factor at 2.5 A from 39 to 31%, with uniform temperature factors and no solvent molecules and with similar stereochemistry; the comparable value for the manually refined structure is 27.9%. Errors in backbone and sidechain positions up to about 3 A are corrected by the method. The error in backbone positions for roughly 85% of the initial structure is within this range, and in these regions the r.m.s. backbone error is reduced from 1.1 to 0.4 A. For the rest of the structure, including a region which was incorrectly built due to a sequence error, the procedure does not yield any improvement and manual intervention appears to be required. Nevertheless, the overall improvement in the structure results in electron density maps that are easier to interpret and permit identification of the errors in the structure. The general utility of the simulated annealing methodology in X-ray refinement is discussed.
最近开发的通过带有模拟退火的分子动力学进行结构因子精修的方法[布吕格、库里安和卡尔普拉斯（1987年）。《科学》，235卷，458 - 460页]在含有118个残基的肌红蛋白上进行了测试。最近已发表了该蛋白在1.3/1.7埃分辨率下的高度精修结构[谢里夫、亨德里克森和史密斯（1987年）。《分子生物学杂志》，197卷，273 - 296页]。将其与从该蛋白早期模型开始进行模拟退火精修（无人工干预）的结果进行比较，该早期模型处于传统最小二乘法无法改善结构的精修阶段。模拟退火在2.5埃分辨率下将R因子从39%降至31%，温度因子均匀且无溶剂分子，立体化学情况相似；人工精修结构的可比数值为27.9%。该方法校正了主链和侧链位置高达约3埃的误差。初始结构中约85%的主链位置误差在这个范围内，在这些区域主链的均方根误差从1.1埃降至0.4埃。对于结构的其余部分，包括因序列错误而构建错误的一个区域，该程序没有产生任何改善，似乎需要人工干预。然而，结构的整体改善使得电子密度图更易于解读，并能识别结构中的错误。讨论了模拟退火方法在X射线精修中的普遍实用性。
