一些全氟(及多氟)有机化合物蒸汽压的QSPR研究

全氟(及多氟)化合物(PFCs)是环境中普遍存在的新一类持久性有机污染物。对其中有蒸汽压数据的35个全氟(及多氟)化合物进行了HF/6-31G*水平上的结构优化,并在优化结构的基础上进行分子表面静电势及其导出参数的计算。分别用"留一法"交叉验证及外部测试集对模型进行检验。结果表明,分子表面静电势参数结合分子表面积可以很好地表达全氟(及多氟)化合物与其分子结构间的定量关系,所建立的QSPR模型具有较强的稳健性和预测能力,同时也证明了分子静电势在全氟化合物QSPR研究中的适用性。     

结合三维静电势参数研究二取代苯的定量结构－疏水性关系

对含有常见取代基的92个二取代苯化合物进行了结构优化和静电势及其导出参数的计算,运用多元线性回归方法对化合物的疏水常数与分子的结构参数进行了关联.结果表明,分子表面负静电势的加和ΣV－S、分子空间内最负的静电势Vmin、表面最大静电势Vs,max以及分子体积V、极性表面积APS和分子的偶极密度μ/V这六个参数,可以很好地用于表达这些化合物疏水性与分子结构间的定量关系,而不用具体考虑分子中极性基团间的相互作用.用建立起来的QSPR(quantitative structure-property relationship)关系式对111个类似化合物的疏水性进行了预测,获得了满意的结果.     

卤代芳烃的脂水分配系数与分子结构的定量关系

本文通过HMO法计算得到了46个卤代芳烃的部分量子化学参数,同时计算了它们的分子总表面积(TSA),以线性溶解能关系(LSER)理论为基础探讨了化合物的正辛醇/水分配系数与其分子结构间的定量关系,建立了一种良好的分配模型,该模型可准确计算出两种溶剂的表面张力之差。     

反向分子设计方面涌现的新方法

在化学,物理,生物和材料科学中,分子设计是必不可少且无处不在的．然而,由极多候选分子组成的巨大空间需要新颖的优化方法去搜索,以便实现高效的分子设计．本文首先总结了分子设计领域内已发展成熟的优化算法,比如穷举算法、分支定界算法、蒙特卡罗类似算法及基因算法．通过若干有代表性的分子设计实例,我们介绍了上述算法的具体应用．其次,本文主要侧重于介绍最新发展的反向分子设计的策略,比如反向能带结构优化算法以及线性展开原子势场方法,并且对后者展开了详细阐述．线性展开原子势场方法选择了核电吸引势场做为优化变量,因为每个中性分子包含的原子类型和原子的空间位置均由此势场决定．本质上,核电吸引势场决定了分子以及分子的所有化学和物理性质．但是核电吸引势场本身不是一个任意的势场,它必须包含合理的分子结构信息．因此,此势场由原子的或者功能团的核电吸引势场做线性展开．通过优化线性展开系数,所感兴趣的分子性质得以最大化或者最小化,同时每个原子的或者功能团所对应的系数包含了最终分子的组成信息．基于密度泛函理论和一个简单的分子模型,我们成功地应用线性展开原子势场方法优化了分子的超极化率．然而,当所感兴趣的分子性质变得复杂或者线性展开中的功能团变得多样化,分子性质曲面也会包含更多的局部最优值．为了有效地搜索复杂的分子性质曲面,我们发展了梯度引导的蒙特卡罗算法．经典的蒙特卡罗算法每次随机地产生新的分子,而梯度引导的蒙特卡罗利用上述方法构造的分子性质曲面,首先计算当前分子所在处的局部梯度相对于所有官能团的展开系数,然后基于此梯度产生下一个分子,最后利用Metropolis规则接受或者拒绝新产生的分子．换句话说,梯度引导的蒙特卡罗算法是一个“半随机”的算法．我们首先应用梯度引导的蒙特卡罗算法,结合线性展开原子势场方法计算的局部梯度,优化了带有普林环的分子框架的超极化率．此外,对于任何一个可构造出分子性质曲面的全局优化问题,梯度引导的蒙特卡罗算法均可适用．比如,我们应用此算法优化了蛋白质的氨基酸序列并探讨了蛋白质的折叠问题．这些具体的应用实例证明了梯度引导的蒙特卡罗算法能够有效地搜索分子空间,根据所感兴趣的分子性质,筛选出最优的分子．总之,本文综述了反向设计的方法近况及其基本原理,将有助于促进分子设计的进程．     

CPSA与疏水性参数的遗传算法及神经网络法研究

用分子力学计算出“净”原子表面积,并利用量子化学方法计算出化合物的电荷加权部分表面积(CP-SA).在用遗传算法和神经网络法对改进的CPSA与有机醇类化合物的疏水性参数作相关分析时发现,改进的CPSA可有效地用于构效关系研究,且算法简洁易行,两种多元统计方法均得到了满意的结果.     

分子表面随机采样分析法用于药物定量构效关系研究

考虑药物配基与蛋白质受体的3类非键作用模式,利用蒙特卡罗随机采样技术得到了一种分子结构性质表达方法:分子表面随机采样分析(RaSMS).同时,定义了蛋白质原子探针、虚拟受体可及表面、表面随机采样目标面积逼近法等多个相关概念,在理论和算法上对该法进行了可行性分析.在此基础上,对31个标准甾体化合物进行了定量构效关系(QS...     

致癌有机化合物分子片段致癌机理的研究

以有机物的分子连接性指数和微扰分子轨道指数作结构、能量参数,从分析致癌有机物分子片段与生物遗传基因DNA链互补碱基对发生共价交联的构效角度出发,首次得出产生碱基移码型或碱基置换型化学致癌的主要过程是化合物分子片段中活性原子与DNA互补碱基对间氢键的共价结合,显示致癌活性的充分必要条件是碱基对G≡C间有两个氢键与致癌分子片段发生特异交联.对100余种已知致癌物的致癌分子片段进行计算分析,成功地获得了有机物分子片段定量结构-致癌活性的估测模式.     

基于药物分子组装的含有Keggin型金属氧簇的超分子化合物的晶体结构和电化学性质研究

通过水热方法合成了超分子化合物(Hfcz)3(PMo12U40)·3H2O.单晶x射线衍射分析表明化合物结晶于三方晶系,P-3c空间群.化合物中的两种亚单元通过氢键作用形成了3D超分子结构.化合物堆积形成了孔道结构.此外,循环伏安法研究结果表明了化合物展示三个连续的双电子还原过程.     

硫杂蒽酮类光引发剂的紫外光谱特性及量子化学研究

本文研究了十四种烷基、烷氧基取代的硫杂蒽酮类光引发剂的紫外光谱特性，利用量子化学的分子轨道理论圆满地解释了硫杂蒽酮类化合物的紫外吸收波长与其结构的关系。利用具有分子结构逻辑识别功能和分子结构编辑功能的ＣＡＭＴＣ软件，及ＰＰＰ计算程序对十四种硫杂蒽酮类化合物的吸收波长进行了计算，计算的结果和实测值能够很好的吻合。计算得到的线性回归方程对于预测硫杂蒽酮类化合物的最大吸收波长是十分有用的。     

白藜芦醇分子的转动惯量和电偶极矩

通过分子轨道理论和杂化轨道理论推断出较稳定的白藜芦醇分子是平面型分子,然后根据白藜芦醇分子结构特点计算了该化合物的一种稳定异构体的转动惯量,用矢量合成法计算了其电偶极矩,为微波辅助白藜芦醇萃取理论研究提供转动惯量和电偶极矩的数据.     

A rapid method for calculating derivatives of solvent accessible surface areas of molecules

A novel method to calculate the derivatives of solvent accessible surface areas is presented. Unlike earlier analytic methods, which require the molecular topology and the use of global Gauss-Bonnet theorem, this method requires only the fractional accessibilities of surface arcs. We developed an efficient numerical algorithm to calculate the surface arcs by creating a uniform set of points on the circles of intersection between surface atoms. A hierarchical point density doubling scheme led to a logarithmic dependence of Central Processing Unit (CPU) time on the number of points used. This algorithm calculated area derivatives for a 1000-atom protein in 1.5 s on an SGI INDIGO² which were within 2% of the analytic area derivatives calculated with the program ANAREA. This algorithm scales linearly with the number of atoms for large molecules and is easily parallelizable. © 1995 by John Wiley & Sons, Inc.     

Determination of the Molecular Area on a Liquid Surface from Thermodynamic Functions: Application to Alkanes

A method is proposed to calculate the molecular area on the surface of a liquid from thermodynamic parameters such as the molar internal energy, the surface free energy, and the surface entropy. When the method is applied to the series of normal alkanes, it allows calculation of the area of the molecules on these liquid surfaces and to deduce the orientation of these molecules. Moreover, the molecular areas of the first terms of the alkane series and of hydrogen are also obtained by extrapolation.     

Novel computer program for fast exact calculation of accessible and molecular surface areas and average surface curvature

New computer programs, SurfRace and FastSurf, perform fast calculations of the solvent accessible and molecular (solvent excluded) surface areas of macromolecules. Program SurfRace also calculates the areas of cavities inaccessible from the outside. We introduce the definition of average curvature of molecular surface and calculate average molecular surface curvatures for each atom in a structure. All surface area and curvature calculations are analytic and therefore yield exact values of these quantities. High calculation speed of this software is achieved primarily by avoiding computationally expensive mathematical procedures wherever possible and by efficient handling of surface data structures. The programs are written initially in the language C for PCs running Windows 2000/98/NT, but their code is portable to other platforms with only minor changes in input-output procedures. The algorithm is robust and does not ignore either multiplicity or degeneracy of atomic overlaps. Fast, memory-efficient and robust execution make this software attractive for applications both in computationally expensive energy minimization algorithms, such as docking or molecular dynamics simulations, and in stand-alone surface area and curvature calculations.     

分子体积及表面积的Monte Carlo模拟计算

建立了用Ｍｏｎｔｅ Ｃａｒｌｏ方法模拟计算ｖａｎ ｄｅｒ ｗａａｌｓ分子体积和表面积的算法，在一定的置信度条件下，可获得在指定置信限内的期望值，与Ｂｏｄｅｒ算法比较，此算法有更优的精度。     

AGBNP: an analytic implicit solvent model suitable for molecular dynamics simulations and high-resolution modeling

We have developed an implicit solvent effective potential (AGBNP) that is suitable for molecular dynamics simulations and high-resolution modeling. It is based on a novel implementation of the pairwise descreening Generalized Born model for the electrostatic component and a new nonpolar hydration free energy estimator. The nonpolar term consists of an estimator for the solute-solvent van der Waals dispersion energy designed to mimic the continuum solvent solute-solvent van der Waals interaction energy, in addition to a surface area term corresponding to the work of cavity formation. AGBNP makes use of a new parameter-free algorithm to calculate the scaling coefficients used in the pairwise descreening scheme to take into account atomic overlaps. The same algorithm is also used to calculate atomic surface areas. We show that excellent agreement is achieved for the GB self-energies and surface areas in comparison to accurate, but much more expensive, numerical evaluations. The parameter-free approach used in AGBNP and the sensitivity of the AGBNP model with respect to large and small conformational changes makes the model suitable for high-resolution modeling of protein loops and receptor sites as well as high-resolution prediction of the structure and thermodynamics of protein-ligand complexes. We present illustrative results for these kinds of benchmarks. The model is fully analytical with first derivatives and is computationally efficient. It has been incorporated into the IMPACT molecular simulation program.     

Rapid approximation to molecular surface area via the use of Boolean logic and look-up tables

We report the development of a new approximate method of calculating molecular surface areas. Our technique is based upon the method of Sharake and Rupley but incorporates several major advances. First, we represent the state of surface points as bits in a bit string so we can utilize Boolean operations to simultaneously turn off multiple test points in one Boolean AND operation. Second, we use a series of Boolean mask look-up tables to reduce the time complexity of the calculation of molecular surface area down to the same magnitude as doing a potential energy evaluation. When we use a 256 surface point sphere for all of the atoms in BPTI, a 454 nonhydrogen atom protein, and a 1.4-Å solvent probe, we in general underestimate the total solvent-accessible surface area (SASA) by approximately 1.25% with a correlation coefficient of 0.9990 over a wide range of conformations. The average CPU time required to calculate the SASA of a BPTI conformer is 0.58 s on an SGI 4D/220 workstation. We also describe a method by which we can calculate an approximate finite difference SASA gradient for BPTI in 0.79 of CPU time. © 1993 John Wiley & Sons, Inc.     

SMART: A solvent-accessible triangulated surface generator for molecular graphics and boundary element applications

Summary An algorithm is presented for generating a representation of the solvent-accessible molecular surface as a smooth triangulated manifold. The algorithm, called SMART (SMooth moleculAR surface Triangulator), divides the contact and reentrant portions of the solvent-accessible molecular surface into curvilinear three-sided elements. In contrast to the author's earlier implementation of this general approach [Zauhar, R.J. and Morgan, R.S., J. Comput. Chem., 11 (1990) 603], the SMART algorithm defines elements directly on the appropriate geometric surface types (rather than using interpolation over cubic elements), and has special features to handle highly distorted regions which often appear in deep crevices and internal cavities. While the method is designed for use with boundary element techniques in continuum electrostatics, it can also be applied to the accurate computation of molecular surface areas and volumes, and the generation of shaded surfaces for display with interactive computer graphics. Availability: Programs (in C) for surface generation, area and volume computation are available from the author. Also available is a graphics display program which runs on Silicon Graphics workstations.     

Comparative analysis of isotherms of water vapor adsorption on oxides

Comparative method is suggested for the analysis of water vapor adsorption on the partially dehydroxylated surface of Si, Al, Ti, Zn, etc., oxides. The method removes distortions typical of BET method, usually employed here, allows to calculate correctly the surface area and values of specific adsorption due to the change of surface hydroxy coverage.