A kinematic view of loop closure
A kinematic view of loop closure
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DOI：
10.1002/jcc.10416
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发表时间：
2004-03-01
影响因子：
3
通讯作者：
Dill, KA
中科院分区：
文献类型：
--
作者：
Coutsias, EA;Seok, C;Dill, KA
我们考虑循环闭合的问题，即找到蛋白质分子链段的可能的骨干结构的集合，该链段与几何与前面的部分和后面的部分一致。我们基于在最一般的倾斜旋转器中，基于关于等效旋转器链接的运动学的机器人文献来确定六个扭转的循环构象的问题，以在一个变量中找到16度多项式的真实根。我们为多项式提供了简单的直观视图和派生，其中三对扭转轴都有一个共同点。我们的方法概括了以前的分析环关闭工作的工作，因为扭转角不必是连续的，并且在自由扭转之间允许任何刚性中间的段。我们的方法还允许在键角和肽扭转角的柔韧性较小。这实质上扩大了可溶剂构型的空间，这是通过将方法应用于环状五肽的建模所证明的。我们将进一步申请给两个重要问题。首先，我们表明，该分析环闭合算法可以有效地与现有的环路构建算法相结合，以样品循环超过三个残基。其次，我们表明，当应用于八遗词环的全局最小化时，通过采用循环闭合算法产生的局部移动来使蒙特卡洛最小化更加有效。我们的循环封闭算法可在http：// dillgroup上自由获得。 ucsf.edu/loop_closure/。 （c）2004年Wiley期刊公司
We consider the problem of loop closure, i.e., of finding the ensemble of possible backbone structures of a chain segment of a protein molecule that is geometrically consistent with preceding and following parts of the chain whose structures are given. We reduce this problem of determining the loop conformations of six torsions to finding the real roots of a 16th degree polynomial in one variable, based on the robotics literature on the kinematics of the equivalent rotator linkage in the most general case of oblique rotators. We provide a simple intuitive view and derivation of the polynomial for the case in which each of the three pair of torsional axes has a common point. Our method generalizes previous work on analytical loop closure in that the torsion angles need not be consecutive, and any rigid intervening segments are allowed between the free torsions. Our approach also allows for a small degree of flexibility in the bond angles and the peptide torsion angles; this substantially enlarges the space of solvable configurations as is demonstrated by an application of the method to the modeling of cyclic pentapeptides. We give further applications to two important problems. First, we show that this analytical loop closure algorithm can be efficiently combined with an existing loop-construction algorithm to sample loops longer than three residues. Second, we show that Monte Carlo minimization is made severalfold more efficient by employing the local moves generated by the loop closure algorithm, when applied to the global minimization of an eight-residue loop. Our loop closure algorithm is freely available at http://dillgroup. ucsf.edu/loop_closure/. (C) 2004 Wiley Periodicals, Inc.