变构效应。

IF 7.2 2区 生物学 Q1 BIOPHYSICS
Mateu Montserrat-Canals, Gabriele Cordara, Ute Krengel
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引用次数: 0

摘要

变构描述了生物大分子通过分子将信号从变构位点(不同于原生内源性配体的正构结合位点)传递到功能位点或活性位点的能力。这篇综述首先回顾了变构的历史,并描述了变构的经典例子——血红蛋白,以及其他众所周知的例子(天冬氨酸转氨基甲酰基酶、Lac抑制因子、激酶、g蛋白偶联受体、三磷酸腺苷合成酶和伴侣蛋白)。然后,我们讨论变构的边缘例子,包括内在无序的蛋白质和酶间变构,以及动力学、熵、构象集成和景观对变构机制的影响,以捕捉该领域的本质。此后,我们概述了研究分子机制的核心方法,包括实验技术以及模拟和基于人工智能(AI)的方法。最后,我们回顾了基于变构的药物发现及其挑战和机遇:随着最近基于人工智能的方法的出现,变构化合物将彻底改变药物发现和医学治疗。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Allostery.

Allostery describes the ability of biological macromolecules to transmit signals spatially through the molecule from an allosteric site – a site that is distinct from orthosteric binding sites of primary, endogenous ligands – to the functional or active site. This review starts with a historical overview and a description of the classical example of allostery – hemoglobin – and other well-known examples (aspartate transcarbamoylase, Lac repressor, kinases, G-protein-coupled receptors, adenosine triphosphate synthase, and chaperonin). We then discuss fringe examples of allostery, including intrinsically disordered proteins and inter-enzyme allostery, and the influence of dynamics, entropy, and conformational ensembles and landscapes on allosteric mechanisms, to capture the essence of the field. Thereafter, we give an overview over central methods for investigating molecular mechanisms, covering experimental techniques as well as simulations and artificial intelligence (AI)-based methods. We conclude with a review of allostery-based drug discovery, with its challenges and opportunities: with the recent advent of AI-based methods, allosteric compounds are set to revolutionize drug discovery and medical treatments.

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来源期刊
Quarterly Reviews of Biophysics
Quarterly Reviews of Biophysics 生物-生物物理
CiteScore
12.90
自引率
1.60%
发文量
16
期刊介绍: Quarterly Reviews of Biophysics covers the field of experimental and computational biophysics. Experimental biophysics span across different physics-based measurements such as optical microscopy, super-resolution imaging, electron microscopy, X-ray and neutron diffraction, spectroscopy, calorimetry, thermodynamics and their integrated uses. Computational biophysics includes theory, simulations, bioinformatics and system analysis. These biophysical methodologies are used to discover the structure, function and physiology of biological systems in varying complexities from cells, organelles, membranes, protein-nucleic acid complexes, molecular machines to molecules. The majority of reviews published are invited from authors who have made significant contributions to the field, who give critical, readable and sometimes controversial accounts of recent progress and problems in their specialty. The journal has long-standing, worldwide reputation, demonstrated by its high ranking in the ISI Science Citation Index, as a forum for general and specialized communication between biophysicists working in different areas. Thematic issues are occasionally published.
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