《天然气化学（英文）》被EI收录

Journal of Natural Gas Chemistry（《天然气化学（英文）》）于2006年被EI（EI工程索引）数据库收录．登录Ei Compendex数据库http：／／www．engineeringvillage2．org．cn可浏览《天然气化学（英文）》2006年以来发表的所有文章的信息．EI数据库侧重提供应用科学和工程领域的文摘索引信息，数据来源于175个学科的5100种工程类期刊、会议论文和技术报告，其影响力与日俱增．《天然气化学（英文）》被EI数据库收录，是对多年来支持我刊的广大作者、读者和审稿专家的回报，也是对我们工作的鼓励．     

含磷蛋白激酶的五配位磷化学结构分析方法

我们在大量实验基础上认为,五配位磷化学结构可能是分析磷酸化蛋白质活化过程的关键结构.本文报道了用一种自主开发的软件对国际蛋白质数据库中收录的激酶及其ATP抑制剂进行分析,寻找其可能形成五配位磷化学结构的结果.国际蛋白数据库(PDB库)已知398个与磷相关蛋白激酶中,有382个蛋白激酶(96%)在活化过程中可能经历了五配位磷化学过渡态.本文中的软件下载地址为:ftp:∥166.111.28.228,软件版权登记号2002SR2943.     

蛋白激酶的五配位磷化学结构分析

基于实验合成的五配位磷氨基酸晶体的平方锥和三角锥的结构, 以及氨基酸侧链参与形成五配位磷化学结构实验的基础上, 设计了软件来搜索国际蛋白数据库中可能形成五配位磷结构的含磷蛋白. 利用自主编写的软件研究发现, 国际蛋白质数据库(PDB库)收录的398个含磷的蛋白激酶中, 有382个蛋白激酶(96%)在活化过程中可能经历了五配位磷化学过渡态或中间体. 例如1H8E蛋白的Lys16的N_Z原子与GNP2的P原子形成了可能的五配位化学结构, 将该结构与实验得到的氨基酸小分子晶体的实际五配位磷结构进行叠加, 结构符合很好, 相关结构的偏差RMSD值为0.71 Å. 文中的软件下载地址为: ftp://166.111.28.228, 软件版权登记号2002SR2943.     

2006年《天然气化学（英文）》将由DICP与Elsevier出版社合作出版发行

2005年6月7日，中国科学院大连化学物理研究所（DICP）与荷兰Elsevier出版社签订了合作出版发行Journal of Natural Gas Chemistry（JNGC，《天然气化学（英文）》）的协议．从2006年起，Elsevier出版社将负责在Science Direct平台上出版JNGC电子版期刊，并负责此期刊在中国以外国家的发行．另外，JNGC不久将被EI Compendex数据库收录．     

利用多克隆抗体有效识别中草药中抗表皮生长因子抑制剂

用一种已知的抗表皮生长因子受体抑制剂 (piceatannol) 作为半抗原与载体牛血清白蛋白 (BSA) 连接后免疫制备相应的多克隆抗体 (PcAb).利用该多克隆抗体来模拟酶制成亲和色谱柱，从一种藏药粗提物中将包括该半抗原在内的几种结构不同的抗表皮生长因子受体抑制剂识别出来.研究采用前沿亲和色谱-质谱联用技术对样品进行分析，可以直接从中药复杂体系中识别出有效成分并进行鉴定，实现中药有效成分的筛选与鉴定一体化技术.     

基于药效团的血管紧张素转换酶抑制肽的结构优化

采用Discovery Studio2．0中的药效团模型生成方法,产生了基于化学特征的ACE抑制肽的药效团模型．所选择的认为最好的药效团模型（Hypo1）含有5个化学特征（1个阴离子中心、1个氢键受体、1个氢键给体、2个疏水中心）．我们先前采用实验的方法,从蚕蛹蛋白中获得具有ACE抑制活性的六肽分子,本文结合产生的ACE抑制肽药效团模型和分子对接研究,对该六肽分子进行结构优化,以识别六肽中对ACE抑制活性起关键作用的结构部分．结果显示,药效团模型的方法可有效用于ACE抑制肽的结构优化．     

PDB数据库在药物化学课程中的应用

通过2个例子说明了PDB数据库在药物化学教学中的应用。这些应用极大地丰富了课堂教学内容,提高了教学质量。     

金属有机骨架的高通量计算筛选研究进展

近年来，金属有机骨架（Metal-Organic Frameworks，MOFs）在气体吸附分离领域的研究获得爆发式增长.随着MOFs数量的剧增，高通量计算筛选成为从大量MOFs中发现高性能目标材料和挖掘其构效关系的最有效研究方法.本综述对MOFs的高通量计算筛选中所用到的数据库包括实验合成的MOFs组成的数据库（experimental MOFs，eMOFs）和计算机设计的MOFs数据库（hypothetical MOFs，hMOFs）、计算筛选方法包括基于分子模拟和机器学习的筛选方法，及其在CH₄储存、H₂储存、CO₂捕捉和其他气体分离领域的研究进展进行了总结.旨在通过梳理该领域的研究进展和思路，明确未来的研究方向和面临的挑战，加快MOFs的研发进程，促进MOFs的商业化应用.     

电感耦合等离子体原子发射光谱分析信息系统的开发 Ⅱ.系统设计与系统评价

讨论了系统设计和系统评价。首先，根据ＩＣＰ－ＡＥＳ中有关信息在计算机中的流动、 转换、储存和处理情况设计了计算机流程图，然后根据数据库规范化的要求对数据库的概念 结构、逻辑结构和物理结构的设计作了讨论。该数据库包括了２８０００余条ＩＣＰ发射谱线的有 关数据。运行结果表明，该系统设计合理，信息量大，且具有方便、实用的用户界面。     

畜禽肉及饲料中氟苯尼考残留免疫分析方法研究

针对动物源性食品及饲料中氟苯尼考的残留问题,通过抗原制备、动物免疫和细胞融合筛选,成功得到可高特异性识别氟苯尼考的单克隆抗体,并建立了氟苯尼考的间接竞争酶联免疫分析（icELISA）方法。经单因素实验优化策略,确定最佳反应条件为：包被抗原质量浓度0.05 μg/mL,抗体质量浓度为0.1 μg/mL,最佳药物、抗体和二抗稀释液均为磷酸缓冲液（PBST）,抗体稀释液吐温－20含量0.05%,竞争反应时间30 min,二抗质量浓度为0.167 μg/mL,二抗反应时间30 min。在该条件下,建立了氟苯尼考的icELISA 检测方法,其IC50为9.48 ng/mL,线性检测范围为1.75 ~ 51.36 ng/mL,检出限（LOD）达0.64 ng/mL,且与氯霉素等结构及功能类似物均无明显交叉反应,特异性良好。实际样品的加标回收率为88.1% ~ 107%,相对标准偏差（RSD）< 15%。将所建立的方法用于畜禽肉及饲料样品的检测,结果与HPLC－MS/MS判定结果一致,说明该方法适用于畜禽产品及饲料中氟苯尼考的残留检测。     

Accurate assessment of the strain energy in a protein-bound drug using QM/MM X-ray refinement and converged quantum chemistry

An ongoing question regarding the energetics of protein‐ligand binding has been; what is the strain energy that a ligand pays (if any) when binding to its protein target? The traditional method to estimate strain energy uses force fields to calculate the energy difference between the ligand bound conformation and its nearest local minimum/global minimum on the gas‐phase or aqueous phase potential energy surface. This makes the implicit assumption that the underlying force field as well as the reference crystal structure is accurate. Herein, we use ibuprofen as a test case and compare MMFF and ab initio QM methods to identify the local and global minimum conformations. Nine low energy conformations were identified with HF/6‐31G* geometry optimization in vacuo. We also obtained highly accurate relative energies for ibuprofen's conformational energy surface based on M06/aug‐cc‐pVXZ (X = D and T), MP2/aug‐cc‐pVXZ (X = D and T) and the MP2/CBS method (with and without solvent corrections). Moreover, we curate and re‐refine the ibuprofen‐protein complex (PDB 2BXG) using QM/MM X‐ray refinement approaches (HF/6‐31G* was the QM method and the MM model was the AMBER force field ff99sb), which were compared with the low energy conformers to calculate the strain energy. The result indicates that there was an 88% reduction in ibuprofen conformation strain using the QM/MM refined structure versus the original PDB ibuprofen conformations. Furthermore, our results indicate that, due to its inherent limitations in estimating electrostatic interactions, force fields are not suitable to gauge strain energy for charged drug molecules like ibuprofen. The present work offers a carefully validated conformational potential energy surface for a drug molecule as well as a reliable QM/MM re‐refined X‐ray structure that can be used to test current structure‐based drug design approaches. © 2011 Wiley Periodicals, Inc. J Comput Chem, 2011     

Development of a microfluidic‐based assay on a novel nitrocellulose platform

A novel microfluidic paper‐based analytical device (μPAD) utilizing a nitrocellulose (NC) membrane to detect IgG antibodies through a colorimetric analysis is described. The μPAD was constructed using layered polyethylene terephthalate (PET) and pressure‐sensitive adhesives (PSA). The biotin labeled Goat Anti‐Mouse IgG antibody was spotted and dried on the NC channel prior to subjecting it to a series of wash solutions (Tris‐tween), increasing concentrations of alkaline phosphatase conjugated to streptavidin (Strep‐ALP), and para‐nitrophenyl phosphate (p‐NPP) realizing a vibrant yellow color. The reaction proceeds for 10 min before applying the p‐NPP stop solution. The device was then dried, scanned, and analyzed yielding a linear range of inverse yellow color intensities versus Strep‐ALP concentrations. The development of this simple μPAD should further facilitate the use of NC in colorimetric assays to detect and quantitate antibodies.     

Exploring the parameter space of the coarse‐grained UNRES force field by random search: Selecting a transferable medium‐resolution force field

We explored the energy‐parameter space of our coarse‐grained UNRES force field for large‐scale ab initio simulations of protein folding, to obtain good initial approximations for hierarchical optimization of the force field with new virtual‐bond‐angle bending and side‐chain‐rotamer potentials which we recently introduced to replace the statistical potentials. 100 sets of energy‐term weights were generated randomly, and good sets were selected by carrying out replica‐exchange molecular dynamics simulations of two peptides with a minimal α‐helical and a minimal β‐hairpin fold, respectively: the tryptophan cage (PDB code: 1L2Y) and tryptophan zipper (PDB code: 1LE1). Eight sets of parameters produced native‐like structures of these two peptides. These eight sets were tested on two larger proteins: the engrailed homeodomain (PDB code: 1ENH) and FBP WW domain (PDB code: 1E0L); two sets were found to produce native‐like conformations of these proteins. These two sets were tested further on a larger set of nine proteins with α or α + β structure and found to locate native‐like structures of most of them. These results demonstrate that, in addition to finding reasonable initial starting points for optimization, an extensive search of parameter space is a powerful method to produce a transferable force field. © 2009 Wiley Periodicals, Inc. J Comput Chem, 2009     

AJICAP: Affinity Peptide Mediated Regiodivergent Functionalization of Native Antibodies

The need for atom‐precise biomolecule modification, and particularly the irreversible formation of covalent bonds to specific amino acids in proteins, has become an essential issue in the fields of pharmaceuticals and chemical biology. For example, antibody–drug conjugates (ADCs) are increasingly common entries into the clinical oncology pipeline. Herein, we report a new method of affinity peptide mediated regiodivergent functionalization (AJICAP?) that enables the synthesis of ADCs from native IgG antibodies. We succeeded in introducing thiol functional groups onto three lysine residues in IgGs using Fc affinity peptide reagents without antibody engineering. A cytotoxic molecule was then connected to the newly introduced thiol group, and both a surface plasmon resonance binding assay and in vivo xenograft mouse model results showed that the resulting ADC could selectively target and kill HER2‐positive cells. Our strategy provides a new approach for constructing complex antibody‐derived biomolecules.     

Differentiation and dating of red ink entries of seals on documents by HPLC and GC/MS

A novel approach for differentiation and dating of red ink entries of seals on documents was developed based on ion‐pairing HPLC (IP‐HPLC) and GC/MS. Sixty‐nine red ink pastes of seals were collected and the chromatographic conditions for separation of the dye components by IP‐HPLC and the volatile additives by GC/MS in the ink entries were optimized. According to the dye components and additives, the ink entries were classified by HPLC with a multi‐wavelength UV detector. The volatile components of the inks were identified by GC/MS and the classification of the ink entries was also investigated based on these volatile additives. The results showed that most of the ink entries of the seals can be differentiated by combining HPLC with a multi‐wavelength detector and GC/MS methods. The degradation of the standard dye mixtures and the compositional changes of the ink entries of seals were investigated in light or natural aging conditions. The results indicated that the dye components decomposed in light or natural storage conditions, while the rates of the degradation depended on the structures of the dye components, the aging conditions, even the additives of the ink pastes. The results also showed that there existed good relationships between the compositional changes of the ink entries and the aging time, which can provide scientific evidences and valuable clues for dating of the ink entries.     

A Sensitive Electrochemical Immunosensor for α‐Fetoprotein Detection with Colloidal Gold‐Based Dentritical Enzyme Complex Amplification

A sensitive and specific electrochemical immunosensor was developed with α‐fetoprotein (AFP) as the model analyte by using gold nanoparticle label for enzymatic catalytic amplification. A self‐assembled monolayer membrane of mercaptopropionic acid (MPA) was firstly formed on the electrode surface through gold‐sulfur interaction. Monoclonal mouse anti‐human AFP was covalently immobilized to serve as the capture antibody. In the presence of the target human AFP, gold nanoparticles coated with polyclonal rabbit anti‐human AFP were bound to the electrode via the formation of a sandwiched complex. With the introduction of goat anti‐rabbit IgG conjugated with alkaline phosphatase, the dentritical enzyme complex was formed through selective interaction of the secondary antibodies with the colloidal gold‐based primary antibody at the electrode, thus affording the possibility of signal amplification for AFP detection. Current response arising from the oxidation of enzymatic product was significantly amplified by the dentritical enzyme complex. The current signal was proportional to the concentration of AFP from 1.0 ng mL^?1 to 500 ng mL^?1 with a detection limit of 0.8 ng mL^?1. This system could be extended to detect other target molecules with the corresponding antibody pairs.     

Immunobinding‐induced alteration in the electrophoretic mobility of proteins: An approach to studying the preconcentration of an acidic protein under cationic isotachophoresis

The objective of this study is to explore an approach for analyzing negatively charged proteins using paper‐based cationic ITP. The rationale of electrophoretic focusing the target protein with negative charges under unfavorable cationic ITP condition is to modify the electrophoretic mobility of the target protein through antigen‐antibody immunobinding. Cationic ITP was performed on a paper‐based analytical device that was fabricated using fiberglass paper. The paper matrix was modified with (3‐aminopropyl)trimethoxysilane to minimize sample attraction to the surface for cationic ITP. Negatively charged BSA was used as the model target protein for the cationic ITP experiments. No electrophoretic mobility was observed for BSA‐only samples during cationic ITP experimental condition. However, the presence of a primary antibody to BSA significantly improved the electrokinetic behavior of the target protein. Adding a secondary antibody conjugated with amine‐rich quantum dots to the sample further facilitated the concentrating effect of ITP, reduced experiment time, and elevated the stacking ratio. Under our optimized experimental conditions, the cationic ITP‐based paper device electrophoretically stacked 94% of loaded BSA in less than 7 min. Our results demonstrate that the technique has a broad potential for rapid and cost‐effective isotachphoretic analysis of multiplex protein biomarkers in serum samples at the point of care.     

Detection of Biomarkers for Liver Fibrosis Using High‐Throughput Electrochemical Microimmunosensor

A high‐throughput electrochemical microimmunosensor for the detection of biomarkers for liver fibrosis was developed. The antibodies, hyaluronic acid binding protein (HABP), lamin antibody (a‐LN) and type IV‐collagen antibody (a‐IVC), are immobilized on different electrodes of the microelectrode array by copolymerizing into the partly insulated poly(o‐phenylenediamine) by means of cyclic voltammetry. Electrochemical detection of the corresponding antigen was based on the extent of electrode insulation toward a redox probe (ferrocenemethanol) solubilized in the electrolyte as a result of the formation of the antigen‐antibody complex at the electrode surface. The microimmunosensor exhibits enough sensitivity to detect the three biomarkers at a concentration level down to 3 ng/mL. The microimmunosensor has been applied to real samples, the results agree well with those obtained by radioimmunoassay (RIA). With the possibility of being portable and considering its ease of use, robustness, and simplicity, the microimmunosensor has great potential as a tool for the screening and early detection of liver fibrosis.     

Coupling porous sheathless interface MS with transient‐ITP in neutral capillaries for improved sensitivity in glycopeptide analysis

IgG antibodies are modulated in their function by the specific structure of the N‐glycans attached to their Fc (fragment crystallizable) portions. However, the glycosylation analysis of antigen‐specific IgGs is a challenging task as antibody levels to a given antigen only represent a fraction of the total IgG levels. Here, we investigated the use of a transient‐ITP (t‐ITP)—MS method for highly sensitive IgG1 glycosylation profiling as a complementary method to a high‐throughput nano‐RPLC‐MS method. It was found that t‐ITP‐CZE using neutrally coated separation capillaries with a large volume injection (37% of capillary volume) and interfaced to MS with a sheathless porous sprayer yielded a 40‐fold increase in sensitivity for IgG1 Fc glycopeptide analysis when compared to the conventional strategy. Furthermore, the glycoform profiles found with the t‐ITP‐CZE strategy were comparable to those from nano‐RPLC‐MS. In conclusion, the use of the highly sensitive t‐ITP‐CZE‐MS method will provide information on IgG Fc glycosylation for those samples with IgG1 concentrations below the LODs of the conventional method.     

A new Lamarckian genetic algorithm for flexible ligand‐receptor docking

We present a Lamarckian genetic algorithm (LGA) variant for flexible ligand‐receptor docking which allows to handle a large number of degrees of freedom. Our hybrid method combines a multi‐deme LGA with a recently published gradient‐based method for local optimization of molecular complexes. We compared the performance of our new hybrid method to two non gradient‐based search heuristics on the Astex diverse set for flexible ligand‐receptor docking. Our results show that the novel approach is clearly superior to other LGAs employing a stochastic optimization method. The new algorithm features a shorter run time and gives substantially better results, especially with increasing complexity of the ligands. Thus, it may be used to dock ligands with many rotatable bonds with high efficiency. © 2010 Wiley Periodicals, Inc. J Comput Chem, 2010