在中设计和合成由定量抗真菌活性指导的抗真菌
Jin Zhang1, Xinhao Sun1, Hongwei Zhao1
1School of Public Health/Key Laboratory of Endemic and Ethnic Diseases, Ministry of Education & Key Laboratory of Medical Molecular Biology of Guizhou Province, Guizhou Medical University, Guiyang 561113, China.
Journal of chemical information and modeling
|May 14, 2024
概括
设计有效的抗真菌 (AFP) 现在通过新的抗真菌指数 (AFI) 度量更有效. 这种方法显著提高了开发针对真菌感染的新型抗真菌疗法的成功率.
科学领域:
- 计算化学和生物信息学
- 发现抗微生物药物发现.
- 的设计和合成.
背景情况:
- 抗真菌 (AFPs) 显示出治疗真菌感染的希望,这是由于其广泛的活性和低耐药性.
- 如果没有可靠的方法来量化抗真菌活性,就很难通过计算来设计AFP.
研究的目的:
- 引入一种创新的量化指标,即抗真菌指数 (AFI),用于*in silico* AFP设计.
- 开发和验证一个三步计算方法来设计强大的AFP.
主要方法:
- 开发了一个三步的AFP设计策略:细分,单点突变和使用AFI指标的全球多点优化.
- 对100个假定的AFP序列进行了详尽的搜索,以确定关键的修改策略.
- 合成并实验测试了28种针对四种真菌菌株的计算设计.
主要成果:
- 没有指导的随机序列修改只产生5.97-20.24%的改善抗真菌活性的机会.
- 关键发现包括N端截断,在10-60%区域的修改增强芳香性/疏水性,以及氨酸,氨酸和氨酸的协同作用.
- 在设计具有最小抑制度≤5.00μM的强效AFP方面取得了82.14%的成功率.
结论:
- AFI指标和建议的*in silico*设计方法显著提高了开发新型抗真菌的效率.
- 该研究提供了一种经过验证的计算工具,以加速下一代抗真菌疗法的发现.
- 开发的预测和设计工具可以在 https://antifungipept.chemoinfolab.com.com 上公开访问.
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