Basu Sankar, Assaf Simon S, Teheux Fabian, Rooman Marianne, Pucci Fabrizio
Computational Biology and Bioinformatics, Université Libre de Bruxelles, Brussels, Belgium.
Department of Microbiology, Austosh College, Under University of Calcutta, Kolkata, India.
Front Bioinform. 2021 Dec 2;1:742843. doi: 10.3389/fbinf.2021.742843. eCollection 2021.
Understanding the role of stability strengths and weaknesses in proteins is a key objective for rationalizing their dynamical and functional properties such as conformational changes, catalytic activity, and protein-protein and protein-ligand interactions. We present BRANEart, a new, fast and accurate method to evaluate the per-residue contributions to the overall stability of membrane proteins. It is based on an extended set of recently introduced statistical potentials derived from membrane protein structures, which better describe the stability properties of this class of proteins than standard potentials derived from globular proteins. We defined a per-residue membrane propensity index from combinations of these potentials, which can be used to identify residues which strongly contribute to the stability of the transmembrane region or which would, on the contrary, be more stable in extramembrane regions, or . Large-scale application to membrane and globular proteins sets and application to tests cases show excellent agreement with experimental data. BRANEart thus appears as a useful instrument to analyze in detail the overall stability properties of a target membrane protein, to position it relative to the lipid bilayer, and to rationally modify its biophysical characteristics and function. BRANEart can be freely accessed from http://babylone.3bio.ulb.ac.be/BRANEart.
了解蛋白质稳定性的强弱作用是阐明其动力学和功能特性（如构象变化、催化活性以及蛋白质 - 蛋白质和蛋白质 - 配体相互作用）的关键目标。我们提出了BRANEart，这是一种全新、快速且准确的方法，用于评估每个残基对膜蛋白整体稳定性的贡献。它基于一组扩展的、最近从膜蛋白结构推导出来的统计势，相较于从球状蛋白推导出来的标准势，能更好地描述这类蛋白质的稳定性特性。我们通过这些势的组合定义了一个每个残基的膜倾向性指数，该指数可用于识别对跨膜区域稳定性有强烈贡献的残基，或者相反，在膜外区域更稳定的残基。对膜蛋白和球状蛋白数据集的大规模应用以及对测试案例的应用表明，其与实验数据高度吻合。因此，BRANEart似乎是一种有用的工具，可用于详细分析目标膜蛋白的整体稳定性特性，将其相对于脂质双层定位，并合理改变其生物物理特性和功能。可从http://babylone.3bio.ulb.ac.be/BRANEart免费访问BRANEart。
