A multi-scale numerical approach to study monoclonal antibodies in solution.

IF 6.6 3区 医学 Q1 ENGINEERING, BIOMEDICAL
APL Bioengineering Pub Date : 2024-02-26 eCollection Date: 2024-03-01 DOI:10.1063/5.0186642
Marco Polimeni, Emanuela Zaccarelli, Alessandro Gulotta, Mikael Lund, Anna Stradner, Peter Schurtenberger
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引用次数: 0

Abstract

Developing efficient and robust computational models is essential to improve our understanding of protein solution behavior. This becomes particularly important to tackle the high-concentration regime. In this context, the main challenge is to put forward coarse-grained descriptions able to reduce the level of detail, while retaining key features and relevant information. In this work, we develop an efficient strategy that can be used to investigate and gain insight into monoclonal antibody solutions under different conditions. We use a multi-scale numerical approach, which connects information obtained at all-atom and amino-acid levels to bead models. The latter has the advantage of reproducing the properties of interest while being computationally much faster. Indeed, these models allow us to perform many-protein simulations with a large number of molecules. We can, thus, explore conditions not easily accessible with more detailed descriptions, perform effective comparisons with experimental data up to very high protein concentrations, and efficiently investigate protein-protein interactions and their role in phase behavior and protein self-assembly. Here, a particular emphasis is given to the effects of charges at different ionic strengths.

研究溶液中单克隆抗体的多尺度数值方法。
开发高效、稳健的计算模型对于提高我们对蛋白质溶液行为的理解至关重要。这对于解决高浓度问题尤为重要。在这种情况下,主要的挑战是提出粗粒度描述,以减少细节,同时保留关键特征和相关信息。在这项工作中,我们开发了一种高效策略,可用于研究和深入了解不同条件下的单克隆抗体溶液。我们采用多尺度数值方法,将在全原子和氨基酸水平上获得的信息与珠粒模型联系起来。后者的优点是能再现感兴趣的特性,同时计算速度更快。事实上,通过这些模型,我们可以对大量分子进行多蛋白模拟。因此,我们可以探索更详细描述难以企及的条件,在蛋白质浓度非常高的情况下与实验数据进行有效比较,并有效研究蛋白质与蛋白质之间的相互作用及其在相行为和蛋白质自组装中的作用。这里特别强调不同离子强度下电荷的影响。
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
APL Bioengineering
APL Bioengineering ENGINEERING, BIOMEDICAL-
CiteScore
9.30
自引率
6.70%
发文量
39
审稿时长
19 weeks
期刊介绍: APL Bioengineering is devoted to research at the intersection of biology, physics, and engineering. The journal publishes high-impact manuscripts specific to the understanding and advancement of physics and engineering of biological systems. APL Bioengineering is the new home for the bioengineering and biomedical research communities. APL Bioengineering publishes original research articles, reviews, and perspectives. Topical coverage includes: -Biofabrication and Bioprinting -Biomedical Materials, Sensors, and Imaging -Engineered Living Systems -Cell and Tissue Engineering -Regenerative Medicine -Molecular, Cell, and Tissue Biomechanics -Systems Biology and Computational Biology
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