A comprehensive primer and review of PROTACs and their In Silico design

IF 4.9 2区医学 Q1 COMPUTER SCIENCE, INTERDISCIPLINARY APPLICATIONS

Computer methods and programs in biomedicine Pub Date : 2025-02-26 DOI:10.1016/j.cmpb.2025.108687

Jacopo Zattoni , Paola Vottero , Gea Carena , Chiara Uliveto , Giulia Pozzati , Benedetta Morabito , Ebenezea Gitari , Jack Tuszynski , Maral Aminpour

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引用次数: 0

Abstract

The cutting-edge technique of Proteolysis Targeting Chimeras, or PROTACs, has gained significant attention as a viable approach for specific protein degradation. This innovative technology has vast potential in fields such as cancer therapy and drug development. The development of effective and specific therapies for a range of diseases is within reach with PROTACs, which can target previously "undruggable" proteins while circumventing the off-target effects of conventional small molecule inhibitors. This manuscript aims to discuss the application of in silico techniques to the design of these groundbreaking molecules and develop PROTAC complexes, in order to identify potential PROTAC candidates with favorable drug-like properties. Additionally, this manuscript reviews the strengths and weaknesses of these methods to demonstrate their utility and highlights the challenges and future prospects of in silico PROTAC design. The present review provides a valuable and beginner-friendly resource for researchers and drug developers interested in using in silico methods for PROTAC design, specifically ternary structure prediction.

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proproc及其在硅片上的设计综述

靶向嵌合体蛋白水解（Proteolysis Targeting Chimeras, PROTACs）作为一种可行的特异性蛋白质降解方法，已经引起了人们的广泛关注。这项创新技术在癌症治疗和药物开发等领域具有巨大的潜力。有了PROTACs，针对一系列疾病的有效和特异性治疗方法的开发就触手可及，它可以针对以前“不可药物”的蛋白质，同时绕过传统小分子抑制剂的脱靶效应。本文旨在讨论硅技术在这些突破性分子设计和开发PROTAC复合物中的应用，以确定具有良好药物样特性的潜在PROTAC候选物。此外，本文回顾了这些方法的优点和缺点，以展示它们的实用性，并强调了硅PROTAC设计的挑战和未来前景。本综述为有兴趣使用计算机方法进行PROTAC设计，特别是三元结构预测的研究人员和药物开发人员提供了一个有价值的初学者友好资源。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Computer methods and programs in biomedicine 工程技术-工程：生物医学

CiteScore

12.30

自引率

6.60%

发文量

601

审稿时长

135 days

期刊介绍： To encourage the development of formal computing methods, and their application in biomedical research and medical practice, by illustration of fundamental principles in biomedical informatics research; to stimulate basic research into application software design; to report the state of research of biomedical information processing projects; to report new computer methodologies applied in biomedical areas; the eventual distribution of demonstrable software to avoid duplication of effort; to provide a forum for discussion and improvement of existing software; to optimize contact between national organizations and regional user groups by promoting an international exchange of information on formal methods, standards and software in biomedicine. Computer Methods and Programs in Biomedicine covers computing methodology and software systems derived from computing science for implementation in all aspects of biomedical research and medical practice. It is designed to serve: biochemists; biologists; geneticists; immunologists; neuroscientists; pharmacologists; toxicologists; clinicians; epidemiologists; psychiatrists; psychologists; cardiologists; chemists; (radio)physicists; computer scientists; programmers and systems analysts; biomedical, clinical, electrical and other engineers; teachers of medical informatics and users of educational software.