From oncoproteins to spike proteins: the evaluation of intramolecular stability using hydropathic force field

IF 3 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Computer-Aided Molecular Design Pub Date : 2022-10-31 DOI:10.1007/s10822-022-00477-y

Federica Agosta, Glen E. Kellogg, Pietro Cozzini

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引用次数: 3

Abstract

Evaluation of the intramolecular stability of proteins plays a key role in the comprehension of their biological behavior and mechanism of action. Small structural alterations such as mutations induced by single nucleotide polymorphism can impact biological activity and pharmacological modulation. Covid-19 mutations, that affect viral replication and the susceptibility to antibody neutralization, and the action of antiviral drugs, are just one example. In this work, the intramolecular stability of mutated proteins, like Spike glycoprotein and its complexes with the human target, is evaluated through hydropathic intramolecular energy scoring originally conceived by Abraham and Kellogg based on the “Extension of the fragment method to calculate amino acid zwitterion and side-chain partition coefficients” by Abraham and Leo in Proteins: Struct. Funct. Genet. 1987, 2:130 − 52. HINT is proposed as a fast and reliable tool for the stability evaluation of any mutated system. This work has been written in honor of Prof. Donald J. Abraham (1936–2021).

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从癌蛋白到刺突蛋白:用亲水力场评价分子内稳定性

评价蛋白质的分子内稳定性对理解蛋白质的生物学行为和作用机制具有重要意义。小的结构改变，如突变引起的单核苷酸多态性可以影响生物活性和药理学调节。影响病毒复制和对抗体中和的易感性以及抗病毒药物作用的Covid-19突变只是一个例子。在本研究中，基于Abraham和Leo在《proteins: Struct》中提出的“扩展片段法计算氨基酸两性离子和侧链分配系数”，通过Abraham和Kellogg最初设想的分子内亲水能量评分法来评估突变蛋白(如Spike糖蛋白及其与人类靶标的复合物)的分子内稳定性。功能。热学杂志。1987,2:130−52。提出了一种快速、可靠的对任意突变系统进行稳定性评估的方法。这本书是为了纪念唐纳德·j·亚伯拉罕教授(1936-2021)而写的。

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来源期刊

Journal of Computer-Aided Molecular Design 生物-计算机：跨学科应用

CiteScore

8.00

自引率

8.60%

发文量

审稿时长

3 months

期刊介绍： The Journal of Computer-Aided Molecular Design provides a form for disseminating information on both the theory and the application of computer-based methods in the analysis and design of molecules. The scope of the journal encompasses papers which report new and original research and applications in the following areas: - theoretical chemistry; - computational chemistry; - computer and molecular graphics; - molecular modeling; - protein engineering; - drug design; - expert systems; - general structure-property relationships; - molecular dynamics; - chemical database development and usage.