Proton first: rationalizing a proton transfer in a protein-fragment complex.

IF 3.6 4区医学 Q2 CHEMISTRY, MEDICINAL

ChemMedChem Pub Date : 2025-06-18 DOI:10.1002/cmdc.202500244

Helge Vatheuer, Jonas Paulus, Lisa Johannknecht, Gerald Keller, Rebecca Maria Ziora, Lukas Stelzl, Paul Czodrowski

引用次数: 0

Abstract

We present a combination of experimental and theoretical approaches to decipher the molecular recognition event of benzoic acid complexed with Protein Kinase A. The publicly known crystal structure suggests the protonated form of benzoic acid to be complexed with Protein Kinase A. Such a protonation pattern of is unlikely for benzoic acid in aqueous enviromnent and must be induced by complexation to Protein Kinase A. Unfortunately, isothermal titration calorimetry does not reveal any binding event which might be caused by the low affinity. However, Poisson-Boltzmann calculations and molecular dynamics simulations strengthen the initial hypothesis of a protonated benzoic acid binding to Protein Kinase A.

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质子优先：使蛋白质片段复合物中的质子转移合理化。

我们提出了一种实验和理论相结合的方法来解释苯甲酸与蛋白激酶a络合的分子识别事件。已知的晶体结构表明苯甲酸的质子化形式与蛋白激酶a络合。这种质子化模式在水环境中不太可能发生，必须通过与蛋白激酶a的络合来诱导。等温滴定量热法未发现任何可能由低亲和力引起的结合事件。然而，泊松-玻尔兹曼计算和分子动力学模拟强化了质子化苯甲酸与蛋白激酶a结合的最初假设。

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

ChemMedChem 医学-药学

CiteScore

6.70

自引率

2.90%

发文量

280

审稿时长

1 months

期刊介绍： Quality research. Outstanding publications. With an impact factor of 3.124 (2019), ChemMedChem is a top journal for research at the interface of chemistry, biology and medicine. It is published on behalf of Chemistry Europe, an association of 16 European chemical societies. ChemMedChem publishes primary as well as critical secondary and tertiary information from authors across and for the world. Its mission is to integrate the wide and flourishing field of medicinal and pharmaceutical sciences, ranging from drug design and discovery to drug development and delivery, from molecular modeling to combinatorial chemistry, from target validation to lead generation and ADMET studies. ChemMedChem typically covers topics on small molecules, therapeutic macromolecules, peptides, peptidomimetics, and aptamers, protein-drug conjugates, nucleic acid therapies, and beginning 2017, nanomedicine, particularly 1) targeted nanodelivery, 2) theranostic nanoparticles, and 3) nanodrugs. Contents ChemMedChem publishes an attractive mixture of: Full Papers and Communications Reviews and Minireviews Patent Reviews Highlights and Concepts Book and Multimedia Reviews.