Loopholes and missing links in protein modeling
Loopholes and missing links in protein modeling
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DOI：
10.1110/ps.072887807
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发表时间：
2007-09-01
期刊：
影响因子：
8
通讯作者：
Krystek, Stanley R., Jr.
中科院分区：
文献类型：
--
作者：
Rossi, Karen A.;Weigelt, Carolyn A.;Krystek, Stanley R., Jr.
本文提供了一个无偏的比较四个商用程序的环路采样，总理，建模，ICM，和Sysphon，其中每一个使用不同的建模协议。该研究评估了结果的质量，并审查了每种方法的相对优势和劣势。待建模的环组的长度从4 - 12个氨基酸变化。用于回路建模的方法可以分为两种方法：从头回路生成（Modeler和Prime）和数据库搜索（Syslog和ICM）。使用建模环与天然结构的比较来确定每种方法的准确度。对于短环长度（4至6个残基），所有方案返回类似的结果，但是随着环长度增加，结果的质量在程序之间变化。引物产生的环对于多达10个残基的环具有RSD < 2.5埃，而其他三种方法在7个残基环处满足2.5埃标准。此外，软件利用二硫键和X射线晶体堆积的能力影响了结果的质量。在最后的分析中，每个程序中排名最高的循环很少是相对于本机模板具有最低RMSD的循环，这揭示了所有程序中正确排名建模循环的弱点。
This paper provides an unbiased comparison of four commercially available programs for loop sampling, Prime, Modeler, ICM, and Sybyl, each of which uses a different modeling protocol. The study assesses the quality of results and examines the relative strengths and weaknesses of each method. The set of loops to be modeled varied in length from 4 -12 amino acids. The approaches used for loop modeling can be classified into two methodologies: ab initio loop generation ( Modeler and Prime) and database searches ( Sybyl and ICM). Comparison of the modeled loops to the native structures was used to determine the accuracy of each method. All of the protocols returned similar results for short loop lengths ( four to six residues), but as loop length increased, the quality of the results varied among the programs. Prime generated loops with RMSDs < 2.5 angstrom for loops up to 10 residues, while the other three methods met the 2.5 angstrom criteria at seven-residue loops. Additionally, the ability of the software to utilize disulfide bonds and X-ray crystal packing influenced the quality of the results. In the final analysis, the top-ranking loop from each program was rarely the loop with the lowest RMSD with respect to the native template, revealing a weakness in all programs to correctly rank the modeled loops.