Simulation Guided Design of a Potentially Hyperactive Ice Nucleating Protein

IF 6.4 2区化学 Q1 CHEMISTRY, MEDICINAL

Journal of Chemical Information and Modeling Pub Date : 2026-07-13 Epub Date: 2026-06-30 DOI:10.1021/acs.jcim.6c00512

Elio A. Cino*, and , D. Peter Tieleman,

{"title":"Simulation Guided Design of a Potentially Hyperactive Ice Nucleating Protein","authors":"Elio A. Cino*,  and , D. Peter Tieleman, ","doi":"10.1021/acs.jcim.6c00512","DOIUrl":null,"url":null,"abstract":"Ice nucleating proteins (INPs) are among the most potent biological catalysts for heterogeneous ice nucleation, triggering freezing at temperatures near 0 °C. Despite structural insights into their β-helical repeat, the molecular mechanisms governing their nucleation efficiency are not fully understood. Extensive atomistic molecular dynamics (MD) simulations (50 μs total) were used to investigate ice nucleation by a modeled Pseudomonas syringae INP (inaV central repeat domain, residues 221–476). Simulations captured ice formation initiating predominantly at YGS and TxT motifs, followed by propagation into stable crystals. Based on these findings, a modified INP with doubled YGS and TxT motifs was designed. This variant displayed faster nucleation kinetics (T50 = 1.9 ± 0.4 μs compared to 3.3 ± 1.8 μs for WT) and ∼28.5% higher ice-like water fractions near key motifs. These findings characterize the YGS motif as a potent water-organizing element and demonstrate the efficacy of MD-driven design in enhancing INP performance for possible energy-saving and biotechnological applications.","PeriodicalId":44,"journal":{"name":"Journal of Chemical Information and Modeling ","volume":"66 13","pages":"7644–7650"},"PeriodicalIF":6.4000,"publicationDate":"2026-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Chemical Information and Modeling ","FirstCategoryId":"92","ListUrlMain":"https://pubs.acs.org/doi/10.1021/acs.jcim.6c00512","RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2026/6/30 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}

引用次数: 0

Abstract

Ice nucleating proteins (INPs) are among the most potent biological catalysts for heterogeneous ice nucleation, triggering freezing at temperatures near 0 °C. Despite structural insights into their β-helical repeat, the molecular mechanisms governing their nucleation efficiency are not fully understood. Extensive atomistic molecular dynamics (MD) simulations (50 μs total) were used to investigate ice nucleation by a modeled Pseudomonas syringae INP (inaV central repeat domain, residues 221–476). Simulations captured ice formation initiating predominantly at YGS and TxT motifs, followed by propagation into stable crystals. Based on these findings, a modified INP with doubled YGS and TxT motifs was designed. This variant displayed faster nucleation kinetics (T₅₀ = 1.9 ± 0.4 μs compared to 3.3 ± 1.8 μs for WT) and ∼28.5% higher ice-like water fractions near key motifs. These findings characterize the YGS motif as a potent water-organizing element and demonstrate the efficacy of MD-driven design in enhancing INP performance for possible energy-saving and biotechnological applications.

Abstract Image

查看原文本刊更多论文

一种潜在的超活性冰核蛋白的模拟指导设计。

冰成核蛋白（INPs）是最有效的非均相冰成核生物催化剂之一，在接近0°C的温度下触发冻结。尽管对其β-螺旋重复序列的结构有深入的了解，但控制其成核效率的分子机制尚未完全了解。采用广泛的原子分子动力学（MD）模拟（50 μs）研究了丁香假单胞菌INP （inaV中心重复结构域，残基221-476）的成核过程。模拟捕捉到冰的形成主要开始于YGS和TxT基序，然后传播成稳定的晶体。在此基础上，设计了双YGS和TxT基序的改良INP。该变体显示出更快的成核动力学（T50 = 1.9±0.4 μs，而WT为3.3±1.8 μs），关键基元附近的冰样水馏分提高了~ 28.5%。这些发现将YGS基序描述为一种有效的水组织元素，并证明了md驱动设计在提高INP性能方面的有效性，从而可能实现节能和生物技术应用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Journal of Chemical Information and Modeling 化学-化学综合

CiteScore

9.80

自引率

10.70%

发文量

529

审稿时长

1.4 months

期刊介绍： The Journal of Chemical Information and Modeling publishes papers reporting new methodology and/or important applications in the fields of chemical informatics and molecular modeling. Specific topics include the representation and computer-based searching of chemical databases, molecular modeling, computer-aided molecular design of new materials, catalysts, or ligands, development of new computational methods or efficient algorithms for chemical software, and biopharmaceutical chemistry including analyses of biological activity and other issues related to drug discovery. Astute chemists, computer scientists, and information specialists look to this monthly’s insightful research studies, programming innovations, and software reviews to keep current with advances in this integral, multidisciplinary field. As a subscriber you’ll stay abreast of database search systems, use of graph theory in chemical problems, substructure search systems, pattern recognition and clustering, analysis of chemical and physical data, molecular modeling, graphics and natural language interfaces, bibliometric and citation analysis, and synthesis design and reactions databases.