经pH和微水分校正的DFT洞察力对黄[7]uril主机-客体热力学:朝着药物纳入预测模型的方向
1Department of Chemistry, Al Al-Bayt University, Mafraq, 25113, Jordan. khaldoun@aabu.edu.jo.
Journal of molecular modeling
|December 9, 2025
概括
预测库库比特[7]uril (CB[7]) 的结合能量是具有挑战性的. 一个新的DFT工作流,包括水化和pH效应,提高了准确性,提供了对主机-客户互动的见解.
科学领域:
- 超分子化学 超分子化学
- 计算化学的计算化学
- 化学热力学化学热力学
背景情况:
- 黄瓜[7]uril (CB[7]) 主机-客户系统表现出强大的结合,但难以准确的热力学预测.
- 含有隐式溶解的标准DFT方法高估了结合的自由能量,这是由于被忽视的因素,如门水和质子平衡等.
研究的目的:
- 开发和验证一个新的DFT工作流程,以准确预测CB[7]主机-客串结合热力学.
- 为管理CB[7]复杂化的驱动力提供化学透明的见解.
主要方法:
- 开发了一个DFT工作流程,其中包含明确的水分子用于门口微水和边缘溶解.
- 用实验 pKa 值对客体质子状态进行了校正,并通过波尔茨曼加权应用了符合平均值.
- 使用RDG/NCI等表面分析非共价相互作用,以了解结合贡献.
主要成果:
- 修正后的DFT模型显著降低了CB[7]客人预测和实验结合的自由能量之间的差异.
- 工作流程成功考虑了微水分,pH效应和形状平均值.
- 分析显示,对于不同类型的客人来说,疏水和静电相互作用的贡献是不同的.
结论:
- 开发的水分和pH意识的DFT协议提供了一个更准确和机械透明的方法来预测CB[7]结合热力学.
- 这个框架可以扩展到更广泛的主机-客户系统和严格的测试.
- 这项研究为CB[7]复杂化中的静电力和疏水力分区提供了有价值的见解.
相关概念视频
02:42Aqueous Solutions and Heats of Hydration
17.3K
Water and other polar molecules are attracted to ions. The electrostatic attraction between an ion and a molecule with a dipole is called an ion-dipole attraction. These attractions play an important role in the dissolution of ionic compounds in water.
When ionic compounds dissolve in water, the ions in the solid separate and disperse uniformly throughout the solution because water molecules surround and solvate the ions, reducing the strong electrostatic forces between them. This process...
When ionic compounds dissolve in water, the ions in the solid separate and disperse uniformly throughout the solution because water molecules surround and solvate the ions, reducing the strong electrostatic forces between them. This process...
17.3K
01:17Pore Transport and Ion-Pair Transport
1.1K
Pore transport and ion-pair formation are critical mechanisms for the absorption and distribution of drugs in the body.
Pore transport, also known as convective transport, is a process where small molecules like urea, water, and sugars rapidly cross cell membranes as though there were channels or pores in the membrane. Although direct microscopic evidence is limited but the concept of pores or channels is widely accepted based on physiological evidence. Despite the lack of direct...
Pore transport, also known as convective transport, is a process where small molecules like urea, water, and sugars rapidly cross cell membranes as though there were channels or pores in the membrane. Although direct microscopic evidence is limited but the concept of pores or channels is widely accepted based on physiological evidence. Despite the lack of direct...
1.1K
01:07Physiological Pharmacokinetic Models: Incorporating Hepatic Transporter-Mediated Clearance
241
Drug transporters are critical in drug absorption, distribution, and excretion processes. They should be included in physiological-based pharmacokinetic (PBPK) models, which help predict human drug disposition. However, predicting this is challenging during drug development, especially when liver transport is involved. However, with a realistic representation of body transport processes, an accurate model may be possible.
A recent model describes pravastatin's hepatobiliary excretion,...
A recent model describes pravastatin's hepatobiliary excretion,...
241
01:13Physiological Pharmacokinetic Models: Assumption with Protein Binding
191
Physiological models with protein binding in pharmacokinetics offer a sophisticated approach to understanding drug disposition. These models consider drug-protein interactions, enabling them to effectively predict drug concentrations in different organs and tissues. This precision aids in accurate drug dosing, providing a significant advantage over conventional models. A key process within these models is equilibration, which ensures that drug concentrations achieve a steady state within the...
191
01:22Factors Influencing Drug Absorption: Physicochemical Parameters
796
The physicochemical characteristics of drugs play a crucial role in formulating stable and bioavailable drug products. The solubility of a drug, governed by the varying pH along the GI tract and its dissociation constant (pKa), is pivotal in determining its ionization state and absorption rate. Notably, weak acids and bases remain unionized and are absorbed more rapidly.
Enhanced drug absorption can be achieved by reducing particle sizes and increasing surface areas, thereby facilitating...
Enhanced drug absorption can be achieved by reducing particle sizes and increasing surface areas, thereby facilitating...
796