{"title":"Comprehensive annotation of mutations in hallmark genes insights into structural and functional implications.","authors":"Ali F Alsulami","doi":"10.1016/j.compbiomed.2024.109588","DOIUrl":null,"url":null,"abstract":"<p><p>Understanding the multifaceted role of hallmark gene mutations in cancer progression is critical for developing targeted therapies. This study comprehensively analyses 344 hallmark gene mutations by mapping them to their three-dimensional protein structures using PDB data and AlphaFold models. Mutations were classified based on their locations, such as protein interfaces, ligand-binding sites, dimer interfaces, protein-DNA interfaces, and core regions. The results reveal that highly frequent mutations are located on the ligand-binding site and protein interface, highlighting their significant impact on protein function and interactions. This holistic approach bridges gaps in existing research, offering insights into the structural impacts of genetic alterations in hallmark genes, thereby informing more effective therapeutic strategies.</p>","PeriodicalId":10578,"journal":{"name":"Computers in biology and medicine","volume":"185 ","pages":"109588"},"PeriodicalIF":7.0000,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Computers in biology and medicine","FirstCategoryId":"5","ListUrlMain":"https://doi.org/10.1016/j.compbiomed.2024.109588","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Understanding the multifaceted role of hallmark gene mutations in cancer progression is critical for developing targeted therapies. This study comprehensively analyses 344 hallmark gene mutations by mapping them to their three-dimensional protein structures using PDB data and AlphaFold models. Mutations were classified based on their locations, such as protein interfaces, ligand-binding sites, dimer interfaces, protein-DNA interfaces, and core regions. The results reveal that highly frequent mutations are located on the ligand-binding site and protein interface, highlighting their significant impact on protein function and interactions. This holistic approach bridges gaps in existing research, offering insights into the structural impacts of genetic alterations in hallmark genes, thereby informing more effective therapeutic strategies.
期刊介绍:
Computers in Biology and Medicine is an international forum for sharing groundbreaking advancements in the use of computers in bioscience and medicine. This journal serves as a medium for communicating essential research, instruction, ideas, and information regarding the rapidly evolving field of computer applications in these domains. By encouraging the exchange of knowledge, we aim to facilitate progress and innovation in the utilization of computers in biology and medicine.