物理化学学报 >> 2013, Vol. 29 >> Issue (06): 1173-1182.doi: 10.3866/PKU.WHXB201303153

热力学,动力学和结构化学 上一篇    下一篇

槲皮素与尿嘧啶和胸腺嘧啶氢键的结合位点

王长生, 刘朋, 于楠   

  1. 辽宁师范大学化学化工学院, 辽宁 大连 116029
  • 收稿日期:2012-12-28 修回日期:2013-03-15 发布日期:2013-05-17
  • 通讯作者: 王长生 E-mail:chwangcs@lnnu.edu.cn
  • 基金资助:

    国家自然科学基金(20973088, 21173109, 21133005); 教育部高等学校博士学科点专项科研基金(20102136110001)和辽宁省优秀人才基金(LR2012037)资助项目

Site-Preference of Uracil and Thymine Hydrogen Bonding to Quercetin

WANG Chang-Sheng, LIU Peng, YU Nan   

  1. School of Chemistry and Chemical Engineering, Liaoning Normal University, Dalian 116029, Liaoning Province, P. R. China
  • Received:2012-12-28 Revised:2013-03-15 Published:2013-05-17
  • Supported by:

    The project was supported by the National Natural Science Foundation of China (20973088, 21173109, 21133005), Specialized Research Fund for the Doctoral Program of Higher Education of China (20102136110001), and Program for Liaoning Excellent Talents in University, China (LR2012037).

摘要:

深入理解药物分子和核酸碱基间的相互作用机制对合理设计研发新型高效药物有重要意义. 本文运用密度泛函理论B3LYP方法对核酸碱基尿嘧啶和胸腺嘧啶与药物分子槲皮素间的氢键相互作用位点进行了研究. 使用B3LYP/6-31G(d)方法优化得到了30个稳定的氢键复合物结构, 使用B3LYP/6-311++G(3df,2p)方法计算了这些复合物的结合能. 研究结果表明, 槲皮素可以使用5个不同的结合位点与尿嘧啶或胸腺嘧啶形成氢键复合物, 尿嘧啶或胸腺嘧啶可以使用3个不同的结合位点与槲皮素形成氢键复合物. 当槲皮素的结合位点固定时, 槲皮素与尿嘧啶的位点u1或胸腺嘧啶的位点t1形成的氢键作用最强, 与位点u2或位点t2形成的氢键强度最弱; 当尿嘧啶或胸腺嘧啶的作用位点固定时, 二者与槲皮素的位点qu1 形成的氢键作用最强, 与位点qu5 作用强度次之, 与位点qu3的作用强度最弱. 分子中原子(AIM)和自然键轨道(NBO)分析计算结果表明, 轨道作用在氢键中起重要作用.

关键词: 槲皮素, 尿嘧啶, 胸腺嘧啶, 氢键, 结合能, 自然键轨道分析, 分子中原子分析

Abstract:

Exploring the binding features between small drug molecules and biomolecules is particularly important because it can provide valuable information for understanding the interaction mechanism and therefore rationally designing, modifying and screening of new drugs. In this paper, the site-preference of the nucleic acid bases uracil and thymine hydrogen bonding to the small medical molecule quercetin is investigated using the density functional theory method. Thirty stable hydrogen-bonded complexes were located at the B3LYP/6-31G(d) level of theory. The binding energies for these complexes were further evaluated at the B3LYP/6-311++G(3df,2p) level of theory with the basis set superposition error corrections. The results indicate that quercetin can interact with uracil or thymine through five binding sites, which herein we refer to as Site qu1, Site qu2, Site qu3, Site qu4, and Site qu5, and uracil (or thymine) can interact with quercetin through three binding sites, which herein we refer to as Site u1, Site u2, and Site u3 (or Site t1, Site t2, and Site t3). We found that once the binding site of quercetin is fixed, the hydrogen bonds formed through uracil Site u1 and thymine Site t1 are the strongest, while those formed through uracil Site u2 and thymine Site t2 are the weakest. When the binding site of uracil or thymine is fixed, the hydrogen bonds formed through the quercetin Site qu1 are the strongest, followed by those formed through quercetin Site qu5, while those formed through quercetin Site qu3 are the weakest. Atoms in molecules (AIM) and natural bond orbital (NBO) analyses were also carried out to explore the interaction nature of these hydrogen-bonded complexes.

Key words: Quercetin, Uracil, Thymine, Hydrogen bond, Binding energy, Natural bond orbital analysis, Atoms in molecules analysis

MSC2000: 

  • O641