Sampling Conformational Ensembles of Highly Dynamic Proteins via Generative Deep Learning.

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Tác giả: Bir Bhanu, Chia-En A Chang, Si-Han Chen, Parisa Fasihianifard, Zhefeng Guo, Ta I Hung, Saisri Padmaja Jonnalagedda, Talant Ruzmetov

Ngôn ngữ: eng

Ký hiệu phân loại: 025.396 *Reclassification

Thông tin xuất bản: United States : Journal of chemical information and modeling , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 493311

Proteins are inherently dynamic, and their conformational ensembles play a crucial role in biological function. Large-scale motions may govern the protein structure-function relationship, and numerous transient but stable conformations of intrinsically disordered proteins (IDPs) can play a crucial role in biological function. Investigating conformational ensembles to understand regulations and disease-related aggregations of IDPs is challenging, both experimentally and computationally. In this paper, we first introduce a deep learning-based model, termed Internal Coordinate Net (ICoN), which learns the physical principles of conformational changes from molecular dynamics simulation data. Second, we selected data points through interpolation in the learned latent space to rapidly identify novel synthetic conformations with sophisticated and large-scale side chains and backbone arrangements. Third, with the highly dynamic amyloid-β
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