Computational design of target-specific linear peptide binders with TransformerBeta
File(s)zhao_2024_PMLR.pdf (7.11 MB)
Published version
Author(s)
Zhao, Haowen
Aprile, Francesco
Bravi, Barbara
Type
Conference Paper
Abstract
The computational prediction and design of peptide binders targeting specific epitopes within disordered protein regions is crucial in biological and biomedical research, yet it remains challenging due to their highly dynamic nature and the scarcity of experimentally solved binding data. To address this problem, we built an unprecedentedly large-scale library of peptide pairs within stable secondary structures (beta sheets), leveraging newly available AlphaFold predicted structures. We then developed a machine learning method based on the Transformer architecture for the design of specific linear binders, in analogy to a language translation task. Our method, TransformerBeta, accurately predicts specific beta strand interactions and samples sequences with beta-sheet-like molecular properties, while capturing interpretable physico-chemical interaction patterns. As such, it can propose specific candidate binders targeting disordered regions for experimental validation to inform protein design.
Date Issued
2024-09-05
Date Acceptance
2024-07-31
Citation
PMLR: Proceedings of Machine Learning Research, 2024, 261, pp.1-27
ISSN
2640-3498
Publisher
MLRearchPress
Start Page
1
End Page
27
Journal / Book Title
PMLR: Proceedings of Machine Learning Research
Volume
261
Copyright Statement
© The authors and PMLR 2024. MLResearchPress.
Source
Machine Learning in Computational Biology
Publication Status
Published
Start Date
2024-09-05
Finish Date
2024-09-06
Coverage Spatial
Seattle, WA, USA