Prediction of SAMPL3 host-guest affinities with the binding energy distribution analysis method (BEDAM).
Prediction of SAMPL3 host-guest affinities with the binding energy distribution analysis method (BEDAM).
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DOI：
10.1007/s10822-012-9552-3
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发表时间：
2012-05
影响因子：
3.5
通讯作者：
Levy, Ronald M.
中科院分区：
文献类型：
--
作者：
Gallicchio, Emilio;Levy, Ronald M.
BEDAM计算描述了预测一系列麻醉药物的结合自由能到最近表征的无环葫芦比脲宿主。作为SAMPL3主客亲和盲挑战的一部分进行的建模预测通常与实验测量结果具有良好的定量一致性。结合自由能的计算值与实测值的相关系数为70%，具有较高的统计显著性。考虑了多种构象立体异构体和客体的质子化态。在酸性模拟条件下得到了较好的一致性和较高的统计置信度。结果表明，如果不考虑重组能和构型熵效应，就不可能达到这种程度的定量一致。在模拟中观察到宿主、客体及其配合物的广泛构象变化，影响了结合自由能的估计和结构预测。作为平行哈密顿复制交换分子动力学BEDAM协议的一部分，引入了构象储层技术，以充分捕获构象变异性。研究表明，这些先进的计算策略导致了这些系统的收敛自由能估计，为利用主客结合自由能数据进行力场验证和开发提供了前景。
BEDAM calculations are described to predict the free energies of binding of a series of anaesthetic drugs to a recently characterized acyclic cucurbituril host. The modeling predictions, conducted as part of the SAMPL3 host-guest affinity blind challenge, are generally in good quantitative agreement with the experimental measurements. The correlation coefficient between computed and measured binding free energies is 70% with high statistical significance. Multiple conformational stereoisomers and protonation states of the guests have been considered. Better agreement is obtained with high statistical confidence under acidic modeling conditions. It is shown that this level of quantitative agreement could have not been reached without taking into account reorganization energy and configurational entropy effects. Extensive conformational variability of the host, the guests and their complexes is observed in the simulations, affecting binding free energy estimates and structural predictions. A conformational reservoir technique is introduced as part of the parallel Hamiltonian replica exchange molecular dynamics BEDAM protocol to fully capture conformational variability. It is shown that these advanced computational strategies lead to converged free energy estimates for these systems, offering the prospect of utilizing host-guest binding free energy data for force field validation and development.
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影响因子：
3.6
作者：
Ma, Da;Zavalij, Peter Y.;Isaacs, Lyle
通讯作者：
Isaacs, Lyle
影响因子：
3
作者：
Gallicchio, Emilio;Levy, Ronald M.;Parashar, Manish
通讯作者：
Parashar, Manish
影响因子：
3.3
作者：
Hagen, Morten;Kim, Byungchan;Berne, B. J.
通讯作者：
Berne, B. J.
影响因子：
15
作者：
Moghaddam S;Yang C;Rekharsky M;Ko YH;Kim K;Inoue Y;Gilson MK
通讯作者：
Gilson MK
DOI：
10.1021/jp807701h
发表时间：
2009-02-26
期刊：
The journal of physical chemistry. B
影响因子：
--
作者：
Deng Y;Roux B
通讯作者：
Roux B