Dataset in support of the paper: BRD4: Quantum mechanical protein-ligand binding free energies using the full-protein DFT-based QM-PBSA method

Electronic Supporting Information for Publication "BRD4: Quantum mechanical protein-ligand binding free energies using the full-protein DFT-based QM-PBSA method" in PCCP, published in Physical Chemistry Chemical Physics Fully quantum mechanical approaches to calculating protein-ligand free energies of binding have the potential to reduce empiricism and explicitly account for all physical interactions responsible for protein-ligand binding. In this study, we show a realistic test of the linear-scaling DFT-based QM-PBSA method to estimate quantum mechanical protein-ligand binding free energies for a set of ligands binding to the pharmaceutical drug-target bromodomain containing protein 4 (BRD4). We show that quantum mechanical QM-PBSA is a significant improvement over traditional MM-PBSA in terms of accuracy against experiment and ligand rank ordering and that the quantum and classical binding energies are converged to a similar degree. We test the interaction entropy and normal mode entropy correction terms to QM- and MM-PBSA. The data set contains input and output files for DFT calculations performed and outputs for MM-PBSA/GBSA and normal mode analysis calculations.

发表于《物理化学化学物理》（Physical Chemistry Chemical Physics，简称PCCP）的论文《BRD4：采用全蛋白密度泛函理论（Density Functional Theory，DFT）基量子力学-泊松玻尔兹曼表面积（Quantum Mechanics-Poisson Boltzmann Surface Area，QM-PBSA）方法计算量子力学蛋白-配体结合自由能》的电子补充材料

用于计算蛋白-配体结合自由能的全量子力学方法，可有效降低经验依赖，并明确涵盖蛋白-配体结合过程中的所有物理相互作用。

本研究针对一系列结合于药物靶点含溴结构域蛋白4（bromodomain containing protein 4，BRD4）的配体，采用基于线性标度密度泛函理论的QM-PBSA方法估算量子力学蛋白-配体结合自由能，并对该方法开展了实际验证测试。

研究表明，相较于传统分子力学-泊松玻尔兹曼表面积（Molecular Mechanics-Poisson Boltzmann Surface Area，MM-PBSA）方法，QM-PBSA在实验吻合度与配体排序准确性上均有显著提升，且量子结合能与经典结合能的收敛程度基本一致。

本研究还测试了QM-PBSA与MM-PBSA的相互作用熵及简正模熵校正项。

本数据集包含已完成的DFT计算的输入与输出文件，以及MM-PBSA/广义玻恩表面积（Generalized Born Surface Area，GBSA）计算和简正模分析计算的输出文件。