A protein folding potential that places the native states of a large number of proteins near a local minimum.
A protein folding potential that places the native states of a large number of proteins near a local minimum.
复制标题
将大量蛋白质的本地状态放置在局部最低限度附近的蛋白质折叠潜力。
DOI：
10.1186/1472-6807-2-4
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发表时间：
2002-08-06
影响因子：
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通讯作者：
Crippen, Gordon M
中科院分区：
文献类型：
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作者：
Chhajer, Mukesh;Crippen, Gordon M
我们提出了一个简单的方法来训练潜在的功能的蛋白质折叠的问题，即使训练使用少量的蛋白质，是能够放置大量的本地构象附近的局部最小值。训练依赖于在二次规划期间通过使用当前电势和使用物理上有意义的目标函数（能量相对于天然构象处的扭转角的导数）使天然构象能量最小化来生成诱饵，以将天然构象放置在局部最小值附近。我们还比较了三种不同类型的能量函数的性能，发现虽然成对能量函数是可训练的，但如果诱饵是通过最小化从天然构象开始的电流势产生的，则溶剂化能量函数本身是不可训练的。当两两相互作用能函数与溶剂化能函数一起使用时，得到了最好的结果。我们能够使用6种蛋白质来训练潜在的函数，其在总共91种蛋白质的局部最小值的约4 μ rmsd内放置总共42种天然构象，在约6 μ rmsd内放置71种天然构象。此外，使用相同的91种蛋白质进行的穿线测试将89种天然构象列为第一，将另外两种列为第二。
We present a simple method to train a potential function for the protein folding problem which, even though trained using a small number of proteins, is able to place a significantly large number of native conformations near a local minimum. The training relies on generating decoys by energy minimization of the native conformations using the current potential and using a physically meaningful objective function (derivative of energy with respect to torsion angles at the native conformation) during the quadratic programming to place the native conformation near a local minimum. We also compare the performance of three different types of energy functions and find that while the pairwise energy function is trainable, a solvation energy function by itself is untrainable if decoys are generated by minimizing the current potential starting at the native conformation. The best results are obtained when a pairwise interaction energy function is used with solvation energy function. We are able to train a potential function using six proteins which places a total of 42 native conformations within ~4 Å rmsd and 71 native conformations within ~6 Å rmsd of a local minimum out of a total of 91 proteins. Furthermore, the threading test using the same 91 proteins ranks 89 native conformations to be first and the other two as second.