相关实验视频

Updated: Jun 18, 2025

From Molecules to Materials: Engineering New Ionic Liquid Crystals Through Halogen Bonding

From Molecules to Materials: Engineering New Ionic Liquid Crystals Through Halogen Bonding

Published on: March 24, 2018

素结合热点作为虚拟查中的约束:5-HT的案例研究

Rafał Kurczab¹

¹Department of Medicinal Chemistry, Maj Institute of Pharmacology, Polish Academy of Sciences, 12 Smetna Street, Krakow 31-343, Poland.

Journal of medicinal chemistry

|July 31, 2024

概括

研究人员确定了在血清素7受体 (5-HT7R) 中素结合的关键氨基酸. 一种虚拟选方法成功预测了具有较高结合亲和力的化合物,增强了药物发现工作.

科学领域:

药用化学医学化学
计算化学计算化学
药理学药理学是指药理学的学科.

背景情况:

血清素7受体 (5-HT7R) 是神经系统疾病的点.
素结合 (XB) 是药物设计中的一个重要的非共价相互作用.
识别特定的氨基酸残留物 (XB热点) 可以指导连接体设计.

研究的目的:

应用分子建模方法来识别5-HT7R中素结合的特权氨基酸.
在虚拟查协议中利用已识别的XB热点来发现新型连接体.
为了验证虚拟选方法的预测准确性.

主要方法:

采用分子建模方法在5-HT7R结构中识别XB热点.
在虚拟查协议中使用已识别的S5x42残留物作为约束.
选了超过800万种商业上可用的化合物,选择了156种用于体外测试.
进行了体外试验,以确定对5-HT7R的结合亲和力.

主要成果:

虚拟查协议确定了63组XSAR具有潜在的5-HT7R活性.
在预测具有增强结合亲和力的基衍生物方面达到68%的准确性.
发现了S5x42与原子之间的素键,使结合亲和力增加了35.4倍.
分子动力学模拟揭示了与S5x42.4的二叉素键的形成.

结论:

分子建模方法有效地识别了5-HT7R中素结合的特权氨基酸.
使用XB热点的虚拟选是发现有力的配体的可行策略.
素结合,特别是与S5x42,显著提高了对5-HT7R的联结亲和力.

更多相关视频

Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors

Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors

Published on: May 9, 2025

Achieving Efficient Fragment Screening at XChem Facility at Diamond Light Source

Achieving Efficient Fragment Screening at XChem Facility at Diamond Light Source

Published on: May 29, 2021

相关概念视频

ortho–para-Directing Deactivators: Halogens

ortho–para-Directing Deactivators: Halogens

Halogens are ortho–para directors. They are more electronegative than carbon. Therefore, as ring substituents, they can withdraw electrons through the inductive effect and deactivate the aromatic ring towards electrophilic substitution. Halogens also have an electron-donating resonance effect on the ring, which influences the orientation of the incoming electrophile. If an electrophile attacks at the ortho or the para position, the halogen donates electrons and stabilizes the intermediate...

VSEPR Theory and the Basic Shapes

VSEPR Theory and the Basic Shapes

Overview of VSEPR Theory

VSEPR Theory and the Effect of Lone Pairs

VSEPR Theory and the Effect of Lone Pairs

Effect of Lone Pairs of Electrons on Molecule Geometry

Hybridization of Atomic Orbitals I

Hybridization of Atomic Orbitals I

The mathematical expression known as the wave function, ψ, contains information about each orbital and the wavelike properties of electrons in an isolated atom. When atoms are bound together in a molecule, the wave functions combine to produce new mathematical descriptions that have different shapes. This process of combining the wave functions for atomic orbitals is called hybridization and is mathematically accomplished by the linear combination of atomic orbitals. The new orbitals that...

Valence Bond Theory

Valence Bond Theory

Overview of Valence Bond Theory

Hydrogen Bonds

Hydrogen Bonds

A hydrogen bond is formed when a weakly positive hydrogen atom already bonded to one electronegative atom (for example, the oxygen in the water molecule) is attracted to another electronegative atom from another polar molecule, such as water (H2O), hydrogen fluoride (HF), or ammonia (NH3). The huge electronegativity difference between the H atom (2.1) and the atom to which it is bonded (4.0 for an F atom, 3.5 for an O atom, or 3.0 for an N atom), combined with the very small size of an H atom...