相关实验视频

Updated: Jul 9, 2025

Multiscale Sampling of a Heterogeneous Water/Metal Catalyst Interface using Density Functional Theory and Force-Field Molecular Dynamics

Multiscale Sampling of a Heterogeneous Water/Metal Catalyst Interface using Density Functional Theory and Force-Field Molecular Dynamics

Published on: April 12, 2019

开发和测试高精度的终点自由能量方法. 3:使用Poisson-Boltzmann方法预测分区系数,并与SAMPL挑战的溶剂可访问表面积模型相结合

Taoyu Niu¹, Xibing He¹, Fengyang Han¹

¹Department of Pharmaceutical Sciences and Computational Chemical Genomics Screening Center, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA 15261, USA. juw79@pitt.edu.

Physical chemistry chemical physics : PCCP

|December 6, 2023

概括

这项研究使用Poisson-Boltzmann/Surface Area (PBSA) 方法准确预测药物分区系数,在SAMPL9挑战中实现了最高准确度的溶解自由能量预测. 这种精细的方法对药物分发分析具有前景.

科学领域:

计算化学计算化学
药物发现药物发现药物发现
物理化学物理化学

背景情况:

准确预测溶解自由能量对于蛋白质 - 配体结合的自由能量至关重要.
分割系数 (log P) 是药物在体内分布的关键物理化学性质.
从溶解自由能量中获得的转移自由能量,直接告知log P计算.

研究的目的:

应用Poisson-Boltzmann (PB) 表面积 (SA) 方法来预测烯/水转移自由能量和分离系数 (log P) 来自无溶解能量 (SFEs).
为改进的非极性SA模型开发和验证与溶剂相关的新型分子表面张力参数.
评估开发方法的预测准确性与已确定的挑战和数据集相比.

主要方法:

使用Poisson-Boltzmann (PB) 表面积 (SA) 方法,使用Open Babel生成的单一溶液构造.
采用使用一般AMBER力场2 (GAFF2) 原子类型基于球体半径的优化边界定义.
开发了与溶剂相关的新分子表面张力参数 (γ和b),用于针对实验性SFEs的烯和环素.

主要成果:

在SAMPL9挑战中,在18个提交项目中,实现了最高的预测准确性 (RMSE 1.52 kcal mol-1) 转移自由能量.
进一步降低预测RMSE到1.33 kcalmol-1使用多重构成策略与分子动力学 (MD) 模拟.
在SAMPL5数据集 (RMSEPBSA = 1.88对RMSECOSMO-RS = 2.11日志单位) 上,在预测循环/水分布系数 (log D) 方面表现优于COSMO-RS.

结论:

精细的Poisson-Boltzmann/表面积 (PBSA) 方法在预测转移自由能量和分割系数方面表现出卓越的准确性.
开发的方法为药物分发属性和错误来源提供了有价值的见解.
这种方法为药物发现和开发提供了一个强大的计算工具.

更多相关视频

Isotopic Effect in Double Proton Transfer Process of Porphycene Investigated by Enhanced QM/MM Method

Isotopic Effect in Double Proton Transfer Process of Porphycene Investigated by Enhanced QM/MM Method

Published on: July 19, 2019

A New Straightforward Method for Lipophilicity logP Measurement using 19F NMR Spectroscopy

A New Straightforward Method for Lipophilicity logP Measurement using 19F NMR Spectroscopy

Published on: January 30, 2019

相关概念视频

Extraction: Partition and Distribution Coefficients

Extraction: Partition and Distribution Coefficients

The distribution law or Nernst's distribution law is the law that governs the distribution of a solute between two immiscible solvents. This law, also known as the partition law, states that if a solute is added to the mixture of two immiscible solvents at a constant temperature, the solute is distributed between the two solvents in such a way that the ratio of solute concentrations in the solvents remains constant at equilibrium.
For extracting a solute from an aqueous phase into an...

Enthalpy of Solution

Enthalpy of Solution

There are two criteria that favor, but do not guarantee, the spontaneous formation of a solution:

Chemical and Solubility Equilibria

Chemical and Solubility Equilibria

The free energy change associated with dissolving a solute in a liter of solvent is called the free energy of a solution, ΔGsolution. The overall ΔGsolution is expressed as the balance of ΔGinteraction against the always-favorable free-energy of mixing, ΔGmixing. Solution formation is favorable if ΔGsolution is less than zero, whereas it is unfavorable if ΔGsolution is greater than zero. In short, for a solution to form and complete dissolution to take place,...

Entropy and Solvation

Entropy and Solvation

The process of surrounding a solute with solvent is called solvation. It involves evenly distributing the solute within the solvent. The rule of thumb for determining a solvent for a given compound is that like dissolves like. A good solvent has molecular characteristics similar to those of the compound to be dissolved. For example, polar solutions dissolve polar solutes, and apolar solvents dissolve apolar solutes. A polar solvent is a solvent that has a high dielectric constant (ϵ...