ProteinReDiff: Complex-based ligand-binding proteins redesign by equivariant diffusion-based generative models.

IF 2.3 2区物理与天体物理 Q3 CHEMISTRY, PHYSICAL

Structural Dynamics-Us Pub Date : 2024-11-25 eCollection Date: 2024-11-01 DOI:10.1063/4.0000271

Viet Thanh Duy Nguyen, Nhan D Nguyen, Truong Son Hy

引用次数: 0

Abstract

Proteins, serving as the fundamental architects of biological processes, interact with ligands to perform a myriad of functions essential for life. Designing functional ligand-binding proteins is pivotal for advancing drug development and enhancing therapeutic efficacy. In this study, we introduce ProteinReDiff, an diffusion framework targeting the redesign of ligand-binding proteins. Using equivariant diffusion-based generative models, ProteinReDiff enables the creation of high-affinity ligand-binding proteins without the need for detailed structural information, leveraging instead the potential of initial protein sequences and ligand SMILES strings. Our evaluations across sequence diversity, structural preservation, and ligand binding affinity underscore ProteinReDiff's potential to advance computational drug discovery and protein engineering.

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ProteinReDiff：基于等变扩散的生成模型的复合体配体结合蛋白的重新设计。

蛋白质，作为生物过程的基本建筑师，与配体相互作用，执行生命所必需的无数功能。设计功能性配体结合蛋白是促进药物开发和提高治疗效果的关键。在这项研究中，我们引入了ProteinReDiff，一个靶向配体结合蛋白重新设计的扩散框架。ProteinReDiff使用基于等变扩散的生成模型，可以创建高亲和力的配体结合蛋白，而不需要详细的结构信息，而是利用初始蛋白质序列和配体SMILES字符串的潜力。我们在序列多样性、结构保存和配体结合亲和力方面的评估强调了ProteinReDiff在推进计算药物发现和蛋白质工程方面的潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Structural Dynamics-Us CHEMISTRY, PHYSICALPHYSICS, ATOMIC, MOLECU-PHYSICS, ATOMIC, MOLECULAR & CHEMICAL

CiteScore

5.50

自引率

3.60%

发文量

审稿时长

16 weeks

期刊介绍： Structural Dynamics focuses on the recent developments in experimental and theoretical methods and techniques that allow a visualization of the electronic and geometric structural changes in real time of chemical, biological, and condensed-matter systems. The community of scientists and engineers working on structural dynamics in such diverse systems often use similar instrumentation and methods. The journal welcomes articles dealing with fundamental problems of electronic and structural dynamics that are tackled by new methods, such as: Time-resolved X-ray and electron diffraction and scattering, Coherent diffractive imaging, Time-resolved X-ray spectroscopies (absorption, emission, resonant inelastic scattering, etc.), Time-resolved electron energy loss spectroscopy (EELS) and electron microscopy, Time-resolved photoelectron spectroscopies (UPS, XPS, ARPES, etc.), Multidimensional spectroscopies in the infrared, the visible and the ultraviolet, Nonlinear spectroscopies in the VUV, the soft and the hard X-ray domains, Theory and computational methods and algorithms for the analysis and description of structuraldynamics and their associated experimental signals. These new methods are enabled by new instrumentation, such as: X-ray free electron lasers, which provide flux, coherence, and time resolution, New sources of ultrashort electron pulses, New sources of ultrashort vacuum ultraviolet (VUV) to hard X-ray pulses, such as high-harmonic generation (HHG) sources or plasma-based sources, New sources of ultrashort infrared and terahertz (THz) radiation, New detectors for X-rays and electrons, New sample handling and delivery schemes, New computational capabilities.