作为一名生物学和医学领域的科学家，您精通英语和简体中文。将以下段落精确地翻译成简体中文，符合学术论文的语言模式，并保持原始陈述的结构： 对作为一种溴域蛋白4-N-末端溴域（BRD4-BD1）抑制剂的吡罗那啶进行体外数据库挖掘、分子对接和分子动力学模拟。
Pyronaridine as a Bromodomain-Containing Protein 4-N-Terminal Bromodomain (BRD4-BD1) Inhibitor: In Silico Database Mining, Molecular Docking, and Molecular Dynamics Simulation.
发表日期：2023 Jul 28
作者：
Mahmoud A A Ibrahim, Mahmoud M H Abdelhamid, Khlood A A Abdeljawaad, Alaa H M Abdelrahman, Gamal A H Mekhemer, Peter A Sidhom, Shaban R M Sayed, Paul W Paré, Mohamed-Elamir F Hegazy, Tamer Shoeib
来源：
Epigenetics & Chromatin
摘要：
BRD4（含有溴结构域的蛋白质4）是一种表观遗传学读头，实现组蛋白蛋白质并促进与癌症进展和非癌疾病（如急性心力衰竭和严重炎症）相关的基因的转录。高度保守的N末端溴结构域（BD1）识别酰化赖氨酸残基以组织基因的表达。因此，BD1对于打断BRD4相互作用是至关重要的，并且是癌症治疗的一个有希望的靶点。为了鉴定新的BD1抑制剂，使用基于体外技术的SuperDRUG2数据库进行了筛选，其中包含了超过4600种制药化合物。首先，评估了AutoDock Vina1.1.2软件用于预测抑制剂-BRD4-BD1结合位构的效率，基于与BRD4-BD1结合的共结晶R6S配体。在数据库筛选中，最有希望的BRD4-BD1抑制剂随后提交到与MM-GBSA方法相结合的分子动力学（MD）模拟中。MM-GBSA计算表明，与阳性对照抑制剂（R6S）相比，在辛脑啶衍生物吡喃奈达啶（SD003509）与BD1的结合中有着有希望的结合能预测（ΔGbinding），为-42.7 kcal/mol，而对于阳性对照抑制剂（R6S）为-41.5 kcal/mol。药动学性质预测了这两种配体的口服生物利用度，而BRD4-BD1结合口袋的动力学分析表明辛脑啶衍生物吡喃奈达啶（pyronaridine）的稳定性更高。这些结果确认了体外研究可以提供对新型蛋白质-配体调节因子的见解，尤其是吡喃奈达啶是一个潜在的癌症药物候选物。
BRD4 (bromodomain-containing protein 4) is an epigenetic reader that realizes histone proteins and promotes the transcription of genes linked to cancer progression and non-cancer diseases such as acute heart failure and severe inflammation. The highly conserved N-terminal bromodomain (BD1) recognizes acylated lysine residues to organize the expression of genes. As such, BD1 is essential for disrupting BRD4 interactions and is a promising target for cancer treatment. To identify new BD1 inhibitors, a SuperDRUG2 database that contains more than 4600 pharmaceutical compounds was screened using in silico techniques. The efficiency of the AutoDock Vina1.1.2 software to anticipate inhibitor-BRD4-BD1 binding poses was first evaluated based on the co-crystallized R6S ligand in complex with BRD4-BD1. From database screening, the most promising BRD4-BD1 inhibitors were subsequently submitted to molecular dynamics (MD) simulations integrated with an MM-GBSA approach. MM-GBSA computations indicated promising BD1 binding with a benzonaphthyridine derivative, pyronaridine (SD003509), with an energy prediction (ΔGbinding) of -42.7 kcal/mol in comparison with -41.5 kcal/mol for a positive control inhibitor (R6S). Pharmacokinetic properties predicted oral bioavailability for both ligands, while post-dynamic analyses of the BRD4-BD1 binding pocket demonstrated greater stability for pyronaridine. These results confirm that in silico studies can provide insight into novel protein-ligand regulators, specifically that pyronaridine is a potential cancer drug candidate.