计算的水化自由能量变得不那么准确,随着分子重量的增加
1Faculty of Pharmacy, Medical University of Sofia, Sofia, Bulgaria.
PloS one
|September 19, 2024
概括
计算机辅助药物设计需要精确的分子动力学力场. 无水化能量 (HFE) 预测显示分子重量的错误越来越大,这对药物发现构成风险.
科学领域:
- 计算化学是一种计算化学.
- 药物的发现和开发.
背景情况:
- 计算机辅助药物设计 (CADD) 承诺更快,更便宜的药物开发.
- 分子动力学 (MD) 力场对于CADD至关重要.
- 对小分子的无水化能量 (HFE) 的准确计算是MD力场的一个重要,但往往不够分析的方面.
研究的目的:
- 为了研究从分子动力学力场中预测水化自由能量 (HFE) 的准确性.
- 确定当前HFE预测方法的潜在缺陷,特别是关于连接物分子重量.
主要方法:
- 对无水化能量 (HFE) 预测错误的分析.
- HFE错误与配体分子量和其他分子描述物的相关性.
- 对MD力场性能进行基准测试.
主要成果:
- 虽然许多研究报告了计算HFEs的高精度 (在2kcal/mol内),但更深入的分析揭示了重大问题.
- HFE预测错误显然取决于联体分子量;较大的分子产生更大的错误.
- 在类似药物的分子量范围内,HFE预测可能不准确5kcal/mol或更多.
结论:
- 目前的分子动力学力场在预测类似药物分子的水合自由能量方面表现出有问题的准确性.
- 观察到的分子量和预测误差之间的相关性凸显了药物发现应用的关键限制.
- 将HFE结果和分子描述符公开,可以促进进一步的研究和改进下一代力场的开发.
更多相关视频
10:52Multiscale Sampling of a Heterogeneous Water/Metal Catalyst Interface using Density Functional Theory and Force-Field Molecular Dynamics
Published on: April 12, 2019
12.8K
08:48High-Resolution Neutron Spectroscopy to Study Picosecond-Nanosecond Dynamics of Proteins and Hydration Water
Published on: April 28, 2022
1.7K
相关概念视频
Aldehydes and Ketones with Water: Hydrate Formation
3.1K
An oxygen-based nucleophile, like water, can undergo addition reactions with aldehydes and ketones. The reaction leads to the formation of hydrates, also referred to as 1,1-diols or geminal diols.
The formation of hydrates is a reversible reaction. Hydrate formation is influenced by steric and electronic factors accompanying the alkyl substituents on the carbonyl group: The rate of hydrate formation increases with a decrease in the number of alkyl groups attached to the carbonyl carbon. Hence,...
The formation of hydrates is a reversible reaction. Hydrate formation is influenced by steric and electronic factors accompanying the alkyl substituents on the carbonyl group: The rate of hydrate formation increases with a decrease in the number of alkyl groups attached to the carbonyl carbon. Hence,...
3.1K
Aqueous Solutions and Heats of Hydration
14.6K
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...
14.6K
Acid-Catalyzed Hydration of Alkenes
13.8K
Alkenes react with water in the presence of an acid to form an alcohol. In the absence of acid, hydration of alkenes does not occur at a significant rate, and the acid is not consumed in the reaction. Therefore, alkene hydration is an acid-catalyzed reaction.
13.8K
Calculating Standard Free Energy Changes
20.8K
The free energy change for a reaction that occurs under the standard conditions of 1 bar pressure and at 298 K is called the standard free energy change. Since free energy is a state function, its value depends only on the conditions of the initial and final states of the system. A convenient and common approach to the calculation of free energy changes for physical and chemical reactions is by use of widely available compilations of standard state thermodynamic data. One method involves the...
20.8K
Molecular Weight of Step-Growth Polymers
2.2K
Step growth polymerization involves bi or multifunctional monomers. Bifunctional monomers react to form linear step growth polymers, whereas multifunctional monomers react to form non-linear or branched polymers.
As the step-growth polymerization involves step-wise condensation of monomers, the molecular weight also builds up eventually. Consequently, high molecular weight polymers are obtained at the late stages of the polymerization, where 99% of monomers have been consumed.
The extent of the...
As the step-growth polymerization involves step-wise condensation of monomers, the molecular weight also builds up eventually. Consequently, high molecular weight polymers are obtained at the late stages of the polymerization, where 99% of monomers have been consumed.
The extent of the...
2.2K
Polymers: Defining Molecular Weight
2.8K
Unlike small molecules with definite molecular weights, polymers are a mixture of individual polymer chains of varying lengths, each with a unique molecular weight. So, the molecular weight of a polymer is expressed as an average value based on the average size of the polymer chains. The two most common forms of averages used for polymers are the number average molecular weight and weight average molecular weight.
The number average molecular weight (Mn) is the summation of the number...
The number average molecular weight (Mn) is the summation of the number...
2.8K
