Phospho-Tune: Enhanced Structural Modeling of Phosphorylated Protein Interactions

Author:

Glukhov ErnestORCID,Averkava Veranika,Kotelnikov Sergei,Stepanenko DaryaORCID,Nguyen Thu,Mitchell Julie C.,Simmerling CarlosORCID,Vajda SandorORCID,Emili AndrewORCID,Padhorny DzmitryORCID,Kozakov DimaORCID

Abstract

AbstractIn computational biology, accurate prediction of phosphopeptide-protein complex structures is essential for understanding cellular functions and advancing drug discovery and personalized medicine. While AlphaFold has significantly improved protein structure prediction, it faces accuracy challenges in predicting structures of complexes involving phosphopeptides possibly due to structural variations introduced by phosphorylation in the peptide component. Our study addresses this limitation by refining AlphaFold to improve its accuracy in modeling these complex structures. We employed weighted metrics for a comprehensive evaluation across various protein families. The enhanced model notably outperforms the original AlphaFold, showing a substantial increase in the weighted average local distance difference test (lDDT) scores for peptides: from 52.74 to 76.51 in the Top 1 model and from 56.32 to 77.91 in the Top 5 model. These advancements not only deepen our understanding of the role of phosphorylation in cellular signaling but also have extensive implications for biological research and the development of innovative therapies.

Publisher

Cold Spring Harbor Laboratory

Reference21 articles.

1. The crucial role of protein phosphorylation in cell signaling and its use as targeted therapy (Review)

2. The Protein Data Bank

3. Lukas Biewald . Experiment tracking with weights and biases, 2020. Software available from wandb.com.

4. Regulation of insulin sensitivity by serine/threonine phosphorylation of insulin receptor substrate proteins IRS1 and IRS2

5. William Falcon and The PyTorch Lightning team. PyTorch Lightning, March 2019.

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3