Molecular dynamics (MD) simulations are coming of age in the study of nucleic acids, including specific tertiary structures such as G-quadruplexes. While being precious for providing structural and dynamic information inaccessible to experiments at the atomistic level of resolution, MD simulations in this field may still be limited by several factors. These include the force fields used, different models for ion parameters, ionic strengths, and water models. We address various aspects of this problem by analyzing and comparing microsecond-long atomistic simulations of the G-quadruplex structure formed by the human immunodeficiency virus long terminal repeat (HIV LTR)-III sequence for which nuclear magnetic resonance (NMR) structures are available. The system is studied in different conditions, systematically varying the ionic strengths, ion numbers, and water models. We comparatively analyze the dynamic behavior of the G-quadruplex motif in various conditions and assess the ability of each simulation to satisfy the nuclear magnetic resonance (NMR)-derived experimental constraints and structural parameters. The conditions taking into account K⁺-ions to neutralize the system charge, mimicking the intracellular ionic strength, and using the four-atom water model are found to be the best in reproducing the experimental NMR constraints and data. Our analysis also reveals that in all of the simulated environments residues belonging to the duplex moiety of HIV LTR-III exhibit the highest flexibility.

中文翻译：

---

研究复杂 G-四链体系统的动力学：深入了解 MD 和 NMR 数据的比较

分子动力学 (MD) 模拟在核酸研究中逐渐成熟，包括特定的三级结构，例如 G-四链体。虽然在提供原子级分辨率的实验无法获得的结构和动态信息方面非常宝贵，但该领域的 MD 模拟仍可能受到几个因素的限制。这些包括使用的力场、离子参数的不同模型、离子强度和水模型。我们通过分析和比较由核磁共振 (NMR) 结构可用的人类免疫缺陷病毒长末端重复 (HIV LTR)-III 序列形成的 G-四链体结构的微秒长原子模拟来解决这个问题的各个方面。该系统在不同条件下进行研究，系统地改变离子强度，离子数和水模型。我们比较分析了 G-四链体基序在各种条件下的动态行为，并评估了每个模拟满足核磁共振 (NMR) 衍生的实验约束和结构参数的能力。考虑到 K 的条件⁺ -离子中和系统电荷，模拟细胞内离子强度，并使用四原子水模型被发现是再现实验 NMR 约束和数据的最佳方法。我们的分析还表明，在所有模拟环境中，属于 HIV LTR-III 双链部分的残基表现出最高的灵活性。