相关实验视频

Updated: Jun 5, 2025

Biosensor-based High Throughput Biopanning and Bioinformatics Analysis Strategy for the Global Validation of Drug-protein Interactions

Biosensor-based High Throughput Biopanning and Bioinformatics Analysis Strategy for the Global Validation of Drug-protein Interactions

Published on: December 1, 2020

蛋白质结合的in silico选,用于开发抗生素耐药性的抑制剂

Xianjin Xu^1,2,3,4, Wei-Ling Kao^2,5,6, Allison Wang^2,5,6

¹Department of Physics, University of Missouri, Columbia, MO 65211, USA.

|December 11, 2024

概括

一种新的计算方法,MDockPeP2_VS,通过整合分子对接和结构保护,使治疗性的大规模片选成为可能. 这加速了药物发现,通过识别TEM-1β-乳酸酶的强有力的抑制剂来证明这一点.

科学领域:

计算化学是一种计算化学.
药物发现药物发现
生物化学生物化学

背景情况:

治疗性对小分子具有优势,包括提高安全性和选择性.
类药物发现的一个主要挑战是缺乏有效的,大规模的蛋白质标选方法.
的灵活性和序列多样性使计算方法复杂化.

研究的目的:

开发一种新的计算方法,MDockPeP2_VS,用于大规模的,基于结构的治疗的片选.
为了解决现有的计算工具在处理的灵活性和序列空间方面的局限性.
为了证明MDockPeP2_VS在识别强抑制剂中的实用性.

主要方法:

分子对接与蛋白质折叠和结之间的结构性保护原则的整合.
利用保存的界面残留物来减少对形状的搜索空间.
MDockPeP2_VS的应用用于选针对大肠杆菌TEM-1β-lactamase的胺抑制剂.

主要成果:

MDockPeP2_VS显著减少了计算时间,使得在片选实用.
该方法成功识别了针对TEM-1β-乳酸酶的潜在抑制剂.
来自in silico屏幕的排名第一的片TF7显示出显著的β-乳酸酶活性抑制,其Ki值为1.37±0.37μM.

结论:

MDockPeP2_VS是一个完全自动化的,大规模的,基于结构的片选软件.
开发的方法加快了治疗性的发现,特别是对于具有挑战性的目标,如抗生素耐药性酶.
该软件是免费提供的,促进进一步的研究在基于的药物发现.

关键词:

抗生素耐药性抗生素耐药性在皮质查中.分子对接的分子对接.类药物发现药物的发现.蛋白的相互作用.

更多相关视频

Identifying Protein-protein Interaction Sites Using Peptide Arrays

Identifying Protein-protein Interaction Sites Using Peptide Arrays

Published on: November 18, 2014

Semi-automated Biopanning of Bacterial Display Libraries for Peptide Affinity Reagent Discovery and Analysis of Resulting Isolates

Semi-automated Biopanning of Bacterial Display Libraries for Peptide Affinity Reagent Discovery and Analysis of Resulting Isolates

Published on: December 6, 2017

相关概念视频

Protein-protein Interfaces

Protein-protein Interfaces

Many proteins form complexes to carry out their functions, making protein-protein interactions (PPIs) essential for an organism's survival. Most PPIs are stabilized by numerous weak noncovalent chemical forces. The physical shape of the interfaces determines the way two proteins interact. Many globular proteins have closely-matching shapes on their surfaces, which form a large number of weak bonds. Additionally, many PPIs occur between two helices or between a surface cleft and a...

Development of Antibiotic Resistance

Development of Antibiotic Resistance

Antibiotic resistance is a major public health concern that arises when bacteria evolve mechanisms to withstand the effects of antibiotic treatments. This resistance can be intrinsic, acquired through genetic mutations, or transferred between bacteria via horizontal gene transfer. The development of antibiotic resistance poses significant challenges in treating bacterial infections and necessitates ongoing research to develop new therapeutic strategies.Intrinsic resistance occurs when bacterial...

Antibiotic Selection

Antibiotic Selection