Rational Proteolysis Targeting Chimera Design Driven by Molecular Modeling and Machine Learning

Wiley Interdisciplinary Reviews Computational Molecular Science, Journal Year: 2025, Volume and Issue: 15(2)

Published: March 1, 2025

ABSTRACT Proteolysis targeting chimera (PROTAC) induces specific protein degradation through the ubiquitin–proteasome system and offers significant advantages over small molecule drugs. They are emerging as a promising avenue, particularly in previously “undruggable” targets. Traditional PROTACs have been discovered large‐scale experimental screening. Extensive research efforts focused on unraveling biological pharmacological functions of PROTACs, with strides made toward transitioning from empirical discovery to rational, structure‐based design strategies. This review provides an overview recent representative computer‐aided drug studies PROTACs. We highlight how utilization targeted database, molecular modeling techniques, machine learning algorithms, computational methods contributes facilitating PROTAC discovery. Furthermore, we conclude achievements field explore challenges future directions. aim offer insights references for rational

Language: Английский

Harnessing the Power of Natural Products for Targeted Protein Degradation

Medicinal Research Reviews, Journal Year: 2025, Volume and Issue: unknown

Published: April 30, 2025

ABSTRACT Natural products have garnered significant attention due to their complex chemical structures and remarkable pharmacological activities. With inherent recognition capabilities for protein surfaces, natural serve as ideal candidates designing proteolysis‐targeting chimeras (PROTACs). The utilization of in PROTAC development offers distinct advantages, including rich diversity, multitarget activities, sustainable sourcing. This comprehensive review explores the vast potential harnessing research. Moreover, discusses application degradant technology, which involves utilizing product‐based compounds selectively degrade disease‐causing proteins, well implementation computer‐aided drug design (CADD) technology identifying suitable targets degradation within realm products. By power leveraging computational tools, PROTACs derived from revolutionize discovery provide innovative therapeutic interventions various diseases.

Language: Английский