MCM-22型分子筛中苯分子吸附行为的分子动力学模拟

用分子动力学方法研究了纯硅ＭＣＭ－２２型分子筛中苯分子的吸附行为。计算结果表明,模拟采用刚性骨架或柔性骨架对苯分子的扩散系数并没有大的差别,这表明在较低吸附值的情况下,分子筛骨架的柔性对苯分子吸附和扩散并没有产生大的影响。     

基于分子动力学模拟和连续介质模型的自由能计算方法*

近些年,基于分子动力学模拟和连续介质模型的自由能计算方法受到了越来越多的关注,其中MM/PBSA就是最具代表性的方法.在MM/PBSA中,体系的焓变采用分子力学(MM)的方法计算得到;溶剂效应中极性部分对自由能的贡献通过解Poisson-Boltzmann(PB)方程的方法计算得到;溶液效应中非极性部分对自由能的贡献则通过分子表面积(SA)计算得到.本文结合我们科研组的工作,就近几年MM/PBSA方法的最新进展做了较为详细的阐述,同时对MM/PBSA的发展前景进行了展望.     

Adaptive neural network consensus tracking control for uncertain multi-agent systems with predefined accuracy

Nonlinear Dynamics - This paper proposes the consensus tracking control problem for a class of uncertain nonlinear multi-agent systems. By using a group of nonnegative functions, an adaptive neural...     

New Born radii deriving method for Generalized Born model

Here we report a method to calculate Born radii, an important parameter used in a Generalized Born model. Traditional methods to derive Born radii are mostly based on a complicated formula, while our method is easier and more direct. Atoms are classified according to their atom type, and the Born radii of each type are obtained by fitting to experimental solvation free energy. The SMARTS language is used for the exact definition of atoms types, and Ullmann's subgraph isomorphism algorithm is used to deduce the environment. A generic algorithm is used for the parameter fitting because of its efficiency in searching a huge phase space, and its results are then optimized by using the conjugate gradient method. The final parameter set is fitting from a training set containing 357 molecules and is tested using a test set of 44 small organic molecules, and the average error is 0.58 kcal/mol for 36 neutral molecules and is 1.67 kcal/mol for 8 ions. The model is further tested under organic molecules, biopolymers, and a protein-inhibitor complex and yields reliable results in all these cases. This method can be used to accelerate molecular docking calculations.     

Molecular docking studies of a group of hydroxamate inhibitors with gelatinase-A by molecular dynamics

We have performed docking and molecular dynamics simulations of hydroxamates complexed with human gelatinase-A (MMP-2) to gain insight into the structural and energetic preferences of these inhibitors. The study was conducted on a selected set of eleven compounds with variation in structure and activity. Molecular dynamics simulations were performed at 300 K for 100 ps with equilibration for 50 ps. The structural analyses of the trajectories indicate that the coordinate bond interactions, the hydrogen bond interactions, the van der Waals interactions as well as the hydrophobic interactions between ligand and receptor are responsible simultaneously for the preference of inhibition and potency. The ligand hydroxamate group is coordinated to the catalytic zinc ion and form stable hydrogen bonds with the carbonyl oxygen of Gly 162. The P1 group makes extensive van der Waals and hydrophobic contacts with the nonpolar side chains of several residues in the S1 subsite, including Leu 197, Val 198, Leu 218 and Tyr 223. Moreover, four to eight hydrogen bonds between hydroxamates and MMP-2 are formed to stabilize the inhibitors in the active site. Compared with the P2 and P3 groups, the P1 groups of inhibitors are oriented regularly, which is produced by the restrain of the S1 subsite. From the relationship between the length of the nonpolar P1 group and the biological activity, we confirm that MMP-2 has a pocket-like S1 subsite, not a channel-like S1 subsite proposed by Kiyama (Kiyama, R. et al., J. Med. Chem. 42 (1999), 1723). The energetic analyses show that the experimental binding free energies can be well correlated with the interactions between the inhibitors and their environments, which could be used as a simple score function to evaluate the binding affinities for other similar hydroxamates. The validity of the force field parameters and the MD simulations can be fully testified by the satisfactory agreements between the experimental structure-activity relationship and the information from the structural and energetic analyses. The information generated from the predicted complexes should be useful for further work in the area of structure-based design of new compounds.     

三种金属硫蛋白动力学稳定性的理论研究

对三类金属硫蛋白（大鼠金属硫蛋白亚型Ⅱ,兔肝金属硫蛋白亚型Ⅰ和兔肝金属硫蛋白亚型Ⅱ）的单体和二聚体进行了水溶液条件下的分子动力学模拟。其中大鼠金属硫蛋白亚型Ⅱ的结构直接来自于晶体数据,兔肝金属硫蛋白亚型Ⅰ和Ⅱ的结构则通过同源蛋白模型搭建。动力学模拟的结果显示,这三种单体在水溶液中都具有相当大的柔性,柔性主要来源于柔性区的氨基酸残基。三类金属硫蛋白单体的动力学模拟均表明α结构域的动力学稳定性都要优于     

ITQ-1分子筛中二甲苯吸附特征的计算机模拟

用巨正则蒙特卡罗模拟研究了邻二甲苯和间二甲苯在ITQ-1分子筛中的吸附特征。模拟结果表明两种吸附质分子在分子筛骨架中的吸附特征不存在明显的差别。从两种吸附质分子在l2员环超笼之间运动的势能曲线,可以说明在通过l0员环窗口时,邻二甲苯和间二甲苯都需要克服较大的势垒,但邻二甲苯需要的激发能量明显大于间二甲苯,计算机模拟以及实验结果表明间二甲苯可以通过l0员环窗口到达分子筛的内部,而邻二甲苯则只能在分子筛的表面发生吸附或扩散。     

Effective band gap reduction of titanium oxide semiconductors by codoping from first‐principles calculations

Doping is an efficient approach to narrow the band gap of TiO₂ and enhance its photocatalytic activity. Here, we perform generalized gradient approximation (GGA)+U calculations to narrow the band gap of TiO₂ by codoping of X (F, N) with transition metals (TM = Fe, Co) to extend the absorption edge to longer visible‐light wavelengths. Our results show that all the codoped systems can narrow the band gap significantly, in particular, (F+Fe)‐codoped system could serve as remarkably better photocatalysts with both narrowing of the band gap and relatively smaller formation energies than those of (F+Co) and (N+TM)‐codoped systems. Our results provide useful guidance for codoped TiO₂ efficient for photocatalytic activity. © 2013 Wiley Periodicals, Inc.     

ADMET evaluation in drug discovery. 11. PharmacoKinetics Knowledge Base (PKKB): a comprehensive database of pharmacokinetic and toxic properties for drugs

Good and extensive experimental ADMET (absorption, distribution, metabolism, excretion, and toxicity) data is critical for developing reliable in silico ADMET models. Here we develop a PharmacoKinetics Knowledge Base (PKKB) to compile comprehensive information about ADMET properties into a single electronic repository. We incorporate more than 10?000 experimental ADMET measurements of 1685 drugs into the PKKB. The ADMET properties in the PKKB include octanol/water partition coefficient, solubility, dissociation constant, intestinal absorption, Caco-2 permeability, human bioavailability, plasma protein binding, blood-plasma partitioning ratio, volume of distribution, metabolism, half-life, excretion, urinary excretion, clearance, toxicity, half lethal dose in rat or mouse, etc. The PKKB provides the most extensive collection of freely available data for ADMET properties up to date. All these ADMET properties, as well as the pharmacological information and the calculated physiochemical properties are integrated into a web-based information system. Eleven separated data sets for octanol/water partition coefficient, solubility, blood-brain partitioning, intestinal absorption, Caco-2 permeability, human oral bioavailability, and P-glycoprotein inhibitors have been provided for free download and can be used directly for ADMET modeling. The PKKB is available online at http://cadd.suda.edu.cn/admet.