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首页> 外文期刊>The journal of physical chemistry, A. Molecules, spectroscopy, kinetics, environment, & general theory >Substituent-Modulated Affinities of Halobenzene Derivatives to the HIV-1 Integrase Recognition Site. Analyses of the Interaction Energies by Parallel Quantum Chemical and Polarizable Molecular Mechanics
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Substituent-Modulated Affinities of Halobenzene Derivatives to the HIV-1 Integrase Recognition Site. Analyses of the Interaction Energies by Parallel Quantum Chemical and Polarizable Molecular Mechanics

机译：卤代苯衍生物对HIV-1整合酶识别位点的取代基调节亲和力。平行量子化学与极化分子力学的相互作用能分析

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摘要

The C-X bond of halobenzenes (X = Cl, Br) has a dual character, its electron density being depleted in its prolongation and built-up on its sides. We have recently considered three protein or nucleic acid recognition sites of halobenzenes and quantified the energy gains that either electron-attracting substituents or electron-donating ones contribute due to such a character (El Hage et al., paper in revision). Nonadditivity was found to impact the total interaction energies. We focus here on one recognition site, that of the HIV-1 integrase, in which the halobenzene ring of the drug elvitegravir is sandwiched between a guanine and a cytosine base. We perform energy-decomposition analyses of the ab initio quantum-chemistry (QC) binding energies of the parent halobenzene ring and its derivatives with this G-C base pair. In these complexes, the nonadditivity of ΔE could be traced back mostly to the polarization contribution Epol. In view of large-scale applications to the entirety of the complex formed between the integrase, the viral DNA, and the whole drug, the analyses were performed in parallel with a polarizable molecular mechanics method, SIBFA. This method could faithfully reproduce most features of the QC energies. This is due to its use of QC-derived distributed multipoles and polarizabilities, which enable us to account for both nonisotropy and nonadditivity.
机译：卤代苯的C-X键（X = Cl，Br）具有双重特征，其电子密度随着其延长而增加，并在其侧面累积。我们最近考虑了卤代苯的三个蛋白质或核酸识别位点，并量化了由于这种特性而吸引电子的取代基或给电子的取代基所贡献的能量增益（El Hage等人，修订版）。发现非可加性影响总相互作用能。我们在这里集中于一个识别位点，即HIV-1整合酶的识别位点，其中药物elvitegravir的卤代苯环被夹在鸟嘌呤和胞嘧啶碱基之间。我们使用该G-C碱基对进行了母体卤代苯环及其衍生物的从头算量子化学（QC）结合能的能量分解分析。在这些络合物中，ΔE的非可加性可以追溯到极化贡献Epol。鉴于大规模应用在整合酶，病毒DNA和整个药物之间形成的复合物的整体，分析与极化分子力学方法SIBFA并行进行。这种方法可以忠实地再现QC能量的大多数特征。这是由于其使用了QC衍生的分布式多极子和极化率，这使我们能够解释非均质性和非可加性。

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