A replica exchange umbrella sampling (REUS) approach to predict host-guest binding free energies in SAMPL8 challenge.
A replica exchange umbrella sampling (REUS) approach to predict host-guest binding free energies in SAMPL8 challenge.
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DOI：
10.1007/s10822-021-00385-7
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发表时间：
2021-05
影响因子：
3.5
通讯作者：
Brooks BR
中科院分区：
文献类型：
--
作者：
Ghorbani M;Hudson PS;Jones MR;Aviat F;Meana-Pañeda R;Klauda JB;Brooks BR
在这项研究中，我们报告了各种滥用药物与葫芦-[8]-脲的结合自由能计算，作为SAMPL 8盲法挑战的一部分。力场参数由不同量子力学理论水平的力匹配得到。使用圆柱形约束的双交换伞采样（雷乌斯）方法来增强主客体结合的采样。结合自由能通过从对称和圆柱形主体的一侧拉动客体分子，然后进入并穿过主体，并从另一侧拉出（双向）来计算，与仅拉动到圆柱形主体内的结合姿势（单向）相比。力匹配MP2参数集的初始结果导致实验值的RMSE为4.68。然而，使用CHARMM广义力场参数和力匹配的PM 6-D 3 H4参数进行的后续研究分别从和的实验中得到了RMSE，这证明了在给出更合适的能量学描述的情况下，雷乌斯在准确计算结合自由能方面的潜力。此外，我们比较了所谓的双向和单向自由能方法的自由能，发现结合自由能是高度相似的。然而，双向方法中的一个问题是主机两侧的轮廓不对称。这主要是由于这些较大系统的采样不足，可以通过更长的采样模拟来避免。总的来说，雷乌斯在束缚自由能计算方面表现出很大的潜力。在线版本包含补充材料，可通过10.1007/s10822-021-00385-7获得。
In this study, we report binding free energy calculations of various drugs-of-abuse to Cucurbit-[8]-uril as part of the SAMPL8 blind challenge. Force-field parameters were obtained from force-matching with different quantum mechanical levels of theory. The Replica Exchange Umbrella Sampling (REUS) approach was used with a cylindrical restraint to enhance the sampling of host–guest binding. Binding free energy was calculated by pulling the guest molecule from one side of the symmetric and cylindrical host, then into and through the host, and out the other side (bidirectional) as compared to pulling only to the bound pose inside the cylindrical host (unidirectional). The initial results with force-matched MP2 parameter set led to RMSE of 4.68 from experimental values. However, the follow-up study with CHARMM generalized force field parameters and force-matched PM6-D3H4 parameters resulted in RMSEs from experiment of and , respectively, which demonstrates the potential of REUS for accurate binding free energy calculation given a more suitable description of energetics. Moreover, we compared the free energies for the so called bidirectional and unidirectional free energy approach and found that the binding free energies were highly similar. However, one issue in the bidirectional approach is the asymmetry of profile on the two sides of the host. This is mainly due to the insufficient sampling for these larger systems and can be avoided by longer sampling simulations. Overall REUS shows great promise for binding free energy calculations. The online version contains supplementary material available at 10.1007/s10822-021-00385-7.
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影响因子：
3
作者：
Mayne, Christopher G.;Saam, Jan;Schulten, Klaus;Tajkhorshid, Emad;Gumbart, James C.
通讯作者：
Gumbart, James C.
影响因子：
3
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