Adaptive Multilevel Splitting Method for Molecular Dynamics Calculation of Benzamidine-Trypsin Dissociation Time.
Adaptive Multilevel Splitting Method for Molecular Dynamics Calculation of Benzamidine-Trypsin Dissociation Time.
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DOI：
10.1021/acs.jctc.6b00277
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发表时间：
2016-06-14
影响因子：
5.5
通讯作者：
Lelièvre T
中科院分区：
文献类型：
--
作者：
Teo I;Mayne CG;Schulten K;Lelièvre T
自适应多电平和（AMS）是一种稀有事件采样方法，它需要最小的参数调整，并且允许对给定稀有事件的过渡路径进行无偏采样。以往的模拟研究已经在Monte Carlo和分子动力学（MD）模拟中验证了AMS计算简单系统过渡时间的效率和准确性。现在，AMS首次应用于蛋白质-配体解离的MD模拟，与之前的测试案例相比，复杂性有了飞跃。令人感兴趣的是解离率，这通常太低，无法用于传统的MD。目前的研究与其他最近的努力一起，在MD中开发先进的采样技术来计算解离率，这在制药领域作为药物功效的指标越来越重要。这里研究的系统，苯胺结合胰蛋白酶，是许多这些努力的一个共同的例子。AMS估计的解离速率为（2.6±2.4）× 102 s−1，与实验值吻合较好。
Adaptive Multilevel Summation (AMS) is a rare event sampling method that requires minimal parameter tuning and that allows unbiased sampling of transition pathways of a given rare event. Previous simulation studies have verified the efficiency and accuracy of AMS in the calculation of transition times for simple systems in both Monte Carlo and molecular dynamics (MD) simulations. Now, AMS is applied for the first time to a MD simulation of protein-ligand dissociation, representing a leap in complexity from the previous test cases. Of interest is the dissociation rate, which is typically too low to be accessible to conventional MD. The present study joins other recent efforts to develop advanced sampling techniques in MD to calculate dissociation rates, which are gaining importance in the pharmaceutical field as indicators of drug efficacy. The system investigated here, benzamidine bound to trypsin, is an example common to many of these efforts. The AMS estimate of the dissociation rate was found to be (2.6 ± 2.4) × 102 s−1, which compares well with the experimental value.
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影响因子：
4.3
作者：
Huang D;Caflisch A
通讯作者：
Caflisch A
DOI：
10.1021/jz101461d
发表时间：
2011
期刊：
The journal of physical chemistry letters
影响因子：
--
作者：
Jiang W;Hardy DJ;Phillips JC;Mackerell AD Jr;Schulten K;Roux B
通讯作者：
Roux B
影响因子：
2.2
作者：
Cerou, F.;Del Moral, P.;Guyader, A.
通讯作者：
Guyader, A.
DOI：
10.1051/proc/201448009
发表时间：
2015-01-01
期刊：
ESAIM. Proceedings and surveys
影响因子：
--
作者：
Aristoff, David;Lelievre, Tony;Teo, Ivan
通讯作者：
Teo, Ivan
影响因子：
5.4
作者：
GLYNN, PW;IGLEHART, DL
通讯作者：
IGLEHART, DL