Using DelPhi capabilities to mimic protein's conformational reorganization with amino acid specific dielectric constants.
Using DelPhi capabilities to mimic protein's conformational reorganization with amino acid specific dielectric constants.
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DOI：
10.4208/cicp.300611.120911s
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发表时间：
2013-01
影响因子：
3.7
通讯作者：
Alexov E
中科院分区：
文献类型：
--
作者：
Wang L;Zhang Z;Rocchia W;Alexov E
许多分子事件与相应蛋白质中发生的或大或小的构象变化有关。对这种变化进行建模是一项挑战，需要大量的计算时间。从静电学的角度来看，如果原因是带电氨基酸的插入或缺失，则这些变化可以被视为响应于静电场变化的局部电荷和偶极子的重组。在这里，我们报告了一个大规模的调查建模的折叠能量的变化，由于单突变涉及带电基团。这使得折叠能量的变化被认为主要是静电的起源，并与德尔菲分配蛋白质的内部介电常数的残基特异性值进行计算。将预测的能量变化与实验测量的257个单突变的折叠能量变化进行基准比较。实验值和预测变化之间的最佳拟合用于找出每种氨基酸的内部介电常数的有效值。预测的折叠自由能的变化与最佳的，氨基酸特异性，介电常数RMSD=0.86千卡/摩尔从实验测量的变化。
Many molecular events are associated with small or large conformational changes occurring in the corresponding proteins. Modeling such changes is a challenge and requires significant amount of computing time. From point of view of electrostatics, these changes can be viewed as a reorganization of local charges and dipoles in response to the changes of the electrostatic field, if the cause is insertion or deletion of a charged amino acid. Here we report a large scale investigation of modeling the changes of the folding energy due to single mutations involving charged group. This allows the changes of the folding energy to be considered mostly electrostatics in origin and to be calculated with DelPhi assigning residue-specific value of the internal dielectric constant of protein. The predicted energy changes are benchmarked against experimentally measured changes of the folding energy on a set of 257 single mutations. The best fit between experimental values and predicted changes is used to find out the effective value of the internal dielectric constant for each type of amino acid. The predicted folding free energy changes with the optimal, amino acid specific, dielectric constants are within RMSD=0.86 kcal/mol from experimentally measured changes.
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影响因子：
3.4
作者：
Dong, F;Zhou, HX
通讯作者：
Zhou, HX
DOI：
10.1046/j.1432-1033.2003.03917.x
发表时间：
2004-01-01
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
Alexov, E
通讯作者：
Alexov, E
影响因子：
5.6
作者：
ANTOSIEWICZ, J;MCCAMMON, JA;GILSON, MK
通讯作者：
GILSON, MK
影响因子：
2.9
作者：
GILSON, MK;HONIG, BH
通讯作者：
HONIG, BH
影响因子：
3.4
作者：
Dong, F;Vijayakumar, M;Zhou, HX
通讯作者：
Zhou, HX