Molecular modelling of ionic liquids: Perfluorinated anionic species with enlarged halogen substitutions

Sun, Zhaoxi; Zheng, Lei; Zhang, Zuo-yuan; Cong, Yalong; Yang, Jingjing; Wang, Xiaohui

doi:10.1016/j.molliq.2023.121599

Cited by 6 publications

(1 citation statement)

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“…The chemical structures of all molecules are either grabbed from the PubChem database or constructed by modifications of existing molecules of similar chemical structures (i.e., template modeling). According to our previous validation of popular charge schemes, the restrained electrostatic potential (RESP) scheme serves as a robust and accurate option for many macrocyclic hosts including cucurbiturils ,, and many other organic and inorganic molecules. − We thus optimize each molecule B3LYP − /6-31G* and then derive RESP charges based on the HF − /6-31G* electrostatic potential. The other parameters of fixed-charge force fields (e.g., bond stretching, torsion, and vdW) are grabbed from the transferable GAFF2 parameter set for all guest molecules, while for the macrocyclic hosts, we apply either GAFF or GAFF2 in our modeling due to the observed differences in host dynamics reported in our recent works. , …”

Section: Computational Detailsmentioning

confidence: 99%

Screening Power of End-Point Free-Energy Calculations in Cucurbituril Host–Guest Systems

Liu,

Zheng,

Qin

et al. 2023

J. Chem. Inf. Model.

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End-point free-energy methods as an indispensable component in virtual screening are commonly recognized as a tool with a certain level of screening power in pharmaceutical research. While a huge number of records could be found for end-point applications in protein–ligand, protein–protein, and protein–DNA complexes from academic and industrial reports, up to now, there is no large-scale benchmark in host–guest complexes supporting the screening power of end-point free-energy techniques. A good benchmark requires a data set of sufficient coverage of pharmaceutically relevant chemical space, a long-time sampling length supporting the trajectory approximation of the ensemble average, and a sufficient sample size of receptor–acceptor pairs to stabilize the performance statistics. In this work, selecting a popular family of macrocyclic hosts named cucurbiturils, we construct a large data set containing 154 host–guest pairs, perform extensive end-point sampling of several hundred nanosecond lengths for each system, and extract the free-energy estimates with a variety of end-point free-energy techniques, including the advanced three-trajectory dielectric-constant-variable regime proposed in our recent work. The best-performing end-point protocol employs GAFF2 for solute descriptions, the three-trajectory end-point sampling regime, and the MM/GBSA Hamiltonian in free-energy extraction, achieving a high ranking metrics of Kendall τ > 0.6, a Pearlman predictive index of ∼0.8, and a high scoring power of Pearson r > 0.8. The current project as the first large-scale systematic benchmark of end-point methods in host–guest complexes in academic publications provides solid evidence of the applicability of end-point techniques and direct guidance of computational setups in practical host–guest systems.

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