异喹啉类化合物抑制肥大细胞脱颗粒活性的3D-QSAR研究

对一组抑制肥大细胞脱颗粒的异喹啉类化合物的活性及毒性进行了3D-QSAR研究,采用距离比较法(DISCO)得到了它们的药效团模型,通过选择不同的叠合方式,建立了相关性很好的比较分子力场分析(CoMFA)模型,其交叉验证参数R^2~cv分别为0.654和0.662,非交叉验证的相关系数分别为0.990与0.983,通过查阅统计量F表,表明活性及毒性模型的置信度都大于99%,显示模型具有较强的预测能力,并在此基础上进行了新活性先导化合物的设计,得到了预测活性高以及预测毒性低的新结构,合成实验正在进行之中。     

Discovery of Anti-SARS Coronavirus Drug Based on Molecular Docking and Database Screening

The active site of 3CL proteinase (3CL^por) for coronavirus was identified by comparing the crystal structures of human and porcine coronavirus. The inhibitor of the main protein of rhinovirus (Ag7088) could bind with 3CL^pro of human coronavirus, then it was selected as the reference for molecular docking and database screening. The ligands from two databases were used to search potential lead structures with molecular docking. Several structures from natural products and ACD-SC databases were found to have lower binding free energy with 3CL^pro than that of Ag7088. These structures have similar hydrophobicity to Ag7088. They have complementary electrostatic potential and hydrogen bond aeceptor and donor with 3CL^pro, showing that the strategy of anti-SARS drug design based on molecular docking and database screening is feasible.     

氢氰酸、异氰酸与水氢键的量子化学研究

用LCAO-MO-SCF的ab initio方法, 在4-31G水平上, 对CNH…OH_2, NCH…OH_2, HNC…HOH, HCN…HOH四种氢键体系进行了能量梯度法的构型优化和计算, 并分别进行了Morokuma能量分解分析, 计算了各作用能对氢键形成的贡献。考察了各作用能随氢键键长的变化情况。从理论上解释了各氢键体系键能强弱次序的变化。在一般情况下,静电作用的大小可以决定氢键键能的强弱次序; 但在某些情况下, 电荷迁移作用也很重要, 需从这两方面综合考虑才能确定键能的强弱次序。     

一元烷基磷(膦)酸酯萃取钴,镍反应中取代基空间效应的经验参数

本文在考察一元烷基磷(膦)酸酯萃取钴、镍反应平衡常数与取代基结构的定量关系的基础上,提出了酸性磷(膦)酸酯萃取钴、镍反应中反映取代基结构空间效应为主的经验参数EPA[Co]和EPA[NI],这些新标度的建立,不仅使我们可用关系式来描述萃取钴、镍的反应性与取代基结构效应的关系,而且也为选择高效镍、钴分离萃取剂提供了新途径。     

From pharmacophore to leads: Bioactive compound discovery via computer-aided techniques

Based on the concept of Green Chemistry, a new procedure of finding bioactive compounds and their synthetic routes by computer-aided techniques was proposed. The procedure consists of pharmacophore search against a 3D structural database of natural products for lead discovery and computer-aided synthesis design for avoiding unuseful synthetic experiments. This work demonstrated that computer aided drug design and synthesis design would help us to make the consideration of environmental concerns systematically, rather than having to deal later with the unnecessary waste chemicals. Thus, it is shown that chemical computer-aided design (CAD) is an indispensable part of Green Chemistry.     

3D-QSAR Study on Apicidin Inhibit Histone Deacetylase

For Histone Deacetylase (HDAC) Inhibitor, four 3D-QSAR models for four types of different activities, were constructed.The cross-valldated q^2 value of CoMFA Model 1 is 0.624 and the noncross-validated r2 value is 0.939. The cross-validated q^2 value of Model 2 for training set is 0.652 and the noncross-validated r^2 value is 0.963. The cross-validated q^2 value for Model 3 is 0.713, with noncross-validated r^2 value 0.947. The crossvalidated q2 value for Model 4 is 0.566 with noncross-validated r^2 value 0.959. Their predicted abilities were validated by different test sets which did not include in training set. Then the relationship between substituents and activities was analyzed by using these models and the main influence elements in different positions (positions 8 and 14) were found. The polar donor electron group of position 8 could increase the activity of inhibition of HDAC, because it could form chelation with the catalytic Zn. Suitable bulk and positive groups at position 14 are favorable to anti-HDAC activity. These models could web interpret the relationship between inhibition activity and apicidin structure affording us important information for structurebased drug design.     

对化学反应数据分类获取反应知识的新方法

尽管已有大量化学反应数据可供使用,但化学家仍常常感到很难便捷地从中得到所需的信息.这主要是由于反应数据库基于结构的检索方法与化学家解决问题的方法相去甚远.为解决这一问题而发展了一种通过对反应进行二级分类得到精细描述反应知识的层次模型的方法.第一次分类时不同的同类反应都在由一组普适性好的称作反应结构一级描述符构成的空间中进行.在第一次分类结果的基础上,得到每一类反应的公共结构特征作为第二次分类的结构描述符,利用它们进行更精细的分类,即可从原始反应数据中得到所需的基核反应.由特定反应、基核反应和基型反应就可将反应知识更合理地组织在同类反应知识库中,使它们得到更好的利用.     

目标化合物析分系统中的重要算法

介绍了目标化合物析分系统中所用到的三个重要算法。它们是：最短拓扑距离的求解、析分过程结束的判别以及合成树的构建。分子结构中任意两个原子之间最短拓扑距离的求解是建立在采用队列数据结构的宽度优先搜索算法基础上的,析分过程结束的判别是由在新Morgan算法基础上产生的化合物的唯一编码和B－树两种算法构成,前者是为了将前体与原料库中每个化合物是否同构的复杂问题简化为码之间的比较问题;后者是一种高效文件组织方式,将代表原料库中化合物的唯一编码作为检索键来组织建库,从而实现对原料库的快速查询,合成树采用的是链表存储方式,每一个结点由六个域组成,且在建树和画树的过程中,均用前序遍历。这些算法是实现析分系统的基础,因此它们的正确设计与高效实现就显得尤为重要。     

计算机化学的主要研究领域及其发展趋势

一、引言 自第一台电子计算机ENLAC诞生至今只有40多年,计算机已经深入到科学研究、工业生产、商务活动等人类社会的一切方面,甚至已进入到家庭,成为现代生活不可缺少的一分部。同样,现代化学也离不开计算机。化学的诸多方面,如在浩如烟海的化学文献中