Structure refinement of protein low resolution models using the GNEIMO constrained dynamics method.
Structure refinement of protein low resolution models using the GNEIMO constrained dynamics method.
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DOI：
10.1021/jp209657n
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发表时间：
2012-03-01
影响因子：
3.3
通讯作者：
Vaidehi, Nagarajan
中科院分区：
文献类型：
--
作者：
Park, In-Hee;Gangupomu, Vamshi;Wagner, Jeffrey;Jain, Abhinandan;Vaidehi, Nagarajan
使用同源建模进行蛋白质结构预测的挑战是缺乏可靠的方法来改进低分辨率同源模型。无约束全原子分子动力学（MD）由于其有限的构象搜索，不能很好地用于结构精化。我们已经开发和测试的约束MD方法，基于广义牛顿-欧拉逆质量算子（GNEIMO）算法的蛋白质结构细化。在该方法中，高频自由度被硬完整约束所取代，蛋白质被建模为由柔性扭转铰链连接的刚体簇的集合。这允许更大的积分时间步长，并增强了构象搜索空间。在这项工作中，我们已经证明了使用的约束自由GNEIMO方法的蛋白质结构的细化，从低分辨率诱饵套同源方法。在8种蛋白质中，每种蛋白质有3个诱饵，我们观察到RMSD比这些蛋白质的已知实验结构提高了约2个数量级。GNEIMO方法还显示了天然样构象的群体密度的富集。此外，我们证明了结构优化使用的“冻结和解冻”聚类方案与GNEIMO框架作为一个可行的工具，以提高本地化的构象搜索。我们已经得出了一个强大的协议的基础上GNEIMO复制品交换方法的蛋白质结构的细化，可以很容易地扩展到其他蛋白质，并可能适用于高通量蛋白质结构的细化。
The challenge in protein structure prediction using homology modeling is the lack of reliable methods to refine the low resolution homology models. Unconstrained all-atom molecular dynamics (MD) does not serve well for structure refinement due to its limited conformational search. We have developed and tested the constrained MD method, based on the Generalized Newton-Euler Inverse Mass Operator (GNEIMO) algorithm for protein structure refinement. In this method, the high-frequency degrees of freedom are replaced with hard holonomic constraints and a protein is modeled as a collection of rigid body clusters connected by flexible torsional hinges. This allows larger integration time steps and enhances the conformational search space. In this work, we have demonstrated the use of a constraint free GNEIMO method for protein structure refinement that starts from low-resolution decoy sets derived from homology methods. In the eight proteins with three decoys for each, we observed an improvement of ~2 Å in the RMSD to the known experimental structures of these proteins. The GNEIMO method also showed enrichment in the population density of native-like conformations. In addition, we demonstrated structural refinement using a “Freeze and Thaw” clustering scheme with the GNEIMO framework as a viable tool for enhancing localized conformational search. We have derived a robust protocol based on the GNEIMO replica exchange method for protein structure refinement that can be readily extended to other proteins and possibly applicable for high throughput protein structure refinement.
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DOI：
10.1073/pnas.072665799
发表时间：
2002-04-16
影响因子：
11.1
作者：
Kussell, E;Shimada, J;Shakhnovich, EI
通讯作者：
Shakhnovich, EI
DOI：
10.1002/prot.340230306
发表时间：
1995-11-01
期刊：
PROTEINS-STRUCTURE FUNCTION AND GENETICS
影响因子：
--
作者：
SALI, A;POTTERTON, L;KARPLUS, M
通讯作者：
KARPLUS, M
影响因子：
5.7
作者：
Robustelli, Paul;Kohlhoff, Kai;Vendruscolo, Michele
通讯作者：
Vendruscolo, Michele
影响因子：
5.6
作者：
ABAGYAN, R;ARGOS, P
通讯作者：
ARGOS, P
影响因子：
6.1
作者：
Priestle, JP
通讯作者：
Priestle, JP