DETERMINATION OF 3-DIMENSIONAL STRUCTURES OF PROTEINS FROM INTERPROTON DISTANCE DATA BY DYNAMICAL SIMULATED ANNEALING FROM A RANDOM ARRAY OF ATOMS - CIRCUMVENTING PROBLEMS ASSOCIATED WITH FOLDING
DETERMINATION OF 3-DIMENSIONAL STRUCTURES OF PROTEINS FROM INTERPROTON DISTANCE DATA BY DYNAMICAL SIMULATED ANNEALING FROM A RANDOM ARRAY OF ATOMS - CIRCUMVENTING PROBLEMS ASSOCIATED WITH FOLDING
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DOI：
10.1016/0014-5793(88)80559-3
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发表时间：
1988-10-24
期刊：
影响因子：
3.5
通讯作者：
GRONENBORN, AM
中科院分区：
文献类型：
--
作者：
NILGES, M;CLORE, GM;GRONENBORN, AM
提出了一种基于模拟退火原理的新实空间方法，用于根据 NMR 数据得出的质子间距离限制来确定蛋白质结构。该方法通过从完全随机的原子阵列开始并在目标函数中适当地引入共价、质子间距离和排斥范德华项的力常数，避免了与迄今为止描述的所有实空间方法相关的折叠问题。通过求解牛顿运动方程在高温下模拟该系统。由于在模拟的早期阶段所有力常数的值都非常低，因此可以克服蛋白质不同折叠之间的能量障碍，并且可靠地定位目标函数的全局最小值。此外，由于原子最初只是弱耦合，因此它们可以基本上独立地移动以满足约束。使用小蛋白质的两个例子来说明该方法，即crambin（46个残基）和马铃薯羧肽酶抑制剂（39个残基）。
A new real space method, based on the principles of simulated annealing, is presented for determining protein structures on the basis of interproton distance restraints derived from NMR data. The method circumvents the folding problem associated with all real space methods described to date, by starting from a completely random array of atoms and introducing the force constants for the covalent, interproton distance and repulsive van der Waals terms in the target function appropriately. The system is simulated at high temperature by solving Newton's equations of motion. As the values of all force constants are very low during the early stages of the simulation, energy barriers between different folds of the protein can be overcome, and the global minimum of the target function is reliably located. Further, because the atoms are initially only weakly coupled, they can move essentially independently to satisfy the restraints. The method is illustrated using two examples of small proteins, namely crambin (46 residues) and potato carboxypeptidase inhibitor (39 residues).