Quantitative Structure-activity Relationships最新文献_第3页

CoMFA, CoMSIA and GRID/GOLPE studies on calcium entry blocking 1,4-dihydropyridines CoMFA, CoMSIA和GRID/GOLPE研究钙进入阻断1,4-二氢吡啶

Quantitative Structure-activity Relationships Pub Date : 2002-08-01 DOI: 10.1002/1521-3838(200208)21:3<239::AID-QSAR239>3.0.CO;2-W

K. Schleifer, E. Tot

{"title":"CoMFA, CoMSIA and GRID/GOLPE studies on calcium entry blocking 1,4-dihydropyridines","authors":"K. Schleifer, E. Tot","doi":"10.1002/1521-3838(200208)21:3<239::AID-QSAR239>3.0.CO;2-W","DOIUrl":"https://doi.org/10.1002/1521-3838(200208)21:3<239::AID-QSAR239>3.0.CO;2-W","url":null,"abstract":"Three different 3D QSAR methods have been applied for a common pharmacophore model of 45 calcium antagonistically active 1,4-dihydropyridines (DHP) in order to find best correlation of interaction fields and biological activity. Analysis for the entire data set yielded r2/q values in a range starting from 0.821/0.620 (GRID/GOLPE) over 0.872/0.600 (CoMFA) to 0.908/0.744 (CoMSIA). The robustness of these models was tested not only via leave-one-out but also by leave-9-out crossvalidations. Furthermore, models were constructed using a subset of 37 DHPs (training set) allowing the prediction of activity for the residual 8 DHPs (test set). The training set yielded r2/q values starting from 0.826/0.672 (GRID/GOLPE) over 0.872/0.540 (CoMFA) to 0.899/0.662 (CoMSIA). For the test set r values from 0.677 (GRID/GOLPE) over 0.639 (CoMFA) to 0.470 (CoMSIA) were calculated. Besides the statistics, each 3D QSAR model yields further information by analysis of the generated contour maps. Consideration of the CoMFA and CoMSIA fields indicates unfavourable steric interactions for bulky moieties in 4′-position. On the other hand, sterical demanding 2′- and 3′-substituents are favourable and the biological activity of DHPs is further increased if these moieties produce a negative electrostatic potential. In contrast, high π-electron density on top of and parallel to the 4-phenyl ring beside the 2′-position is associated with decreasing activity. This could point to repulsive electronic interactions with binding site residues or to the potential of electron-deficient 4-aryl moieties to behave as electron acceptors in a charge transfer (CT) mechanism.","PeriodicalId":20818,"journal":{"name":"Quantitative Structure-activity Relationships","volume":"24 1","pages":"239-248"},"PeriodicalIF":0.0,"publicationDate":"2002-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90755644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 11

Application of Density Functional Theory Based Car-Parrinello Simulations to the Study of Catalytic Processes 基于密度泛函理论的Car-Parrinello模拟在催化过程研究中的应用

Quantitative Structure-activity Relationships Pub Date : 2002-07-01 DOI: 10.1002/1521-3838(200207)21:2<149::AID-QSAR149>3.0.CO;2-#

S. Raugei, Dongsup Kim, M. Klein

引用次数: 2

Exploring Organic Chemistry with DFT: Radical, Organo‐metallic, and Bio‐organic Applications 用DFT探索有机化学:自由基、有机金属和生物有机的应用

Quantitative Structure-activity Relationships Pub Date : 2002-07-01 DOI: 10.1002/1521-3838(200207)21:2<128::AID-QSAR128>3.0.CO;2-B

F. Bernardi, A. Bottoni, M. Garavelli

{"title":"Exploring Organic Chemistry with DFT: Radical, Organo‐metallic, and Bio‐organic Applications","authors":"F. Bernardi, A. Bottoni, M. Garavelli","doi":"10.1002/1521-3838(200207)21:2<128::AID-QSAR128>3.0.CO;2-B","DOIUrl":"https://doi.org/10.1002/1521-3838(200207)21:2<128::AID-QSAR128>3.0.CO;2-B","url":null,"abstract":"In this review we report the results of DFT investigations which have been carried out in different fields of organic and organometallic chemistry, including radical reactivity, structure and reactivity of organometallic compounds, and biochemical/biophysical properties of long chain unsaturated systems. Many of the most popular non-local corrected functionals (e.g. B3LYP, BHLYP, BLYP, BP86) have been benchmarked both versus experimental and high level ab initio (e.g. MP2, MP4, CAS-SCF/CAS-PT2) data, resulting in an impressive agreement. The DFT approach appears to be a powerful tool, which can be used as a valid alternative to more traditional correlated methods, to achieve mechanistic information of chemical/ physical interest in the modelling of organic and biochemical systems. In particular, in the examples selected in this review, we discuss the results obtained for the addition reaction of alkyl radicals to double bonds and for the hydrogen/ chlorine abstraction reaction by alkyl and silyl radicals from various organic substrates. Moreover, binding interactions (i.e. geometries and energies) in organometallic compounds are shown to be satisfactorily reproduced via DFT and examples of nickel-catalyzed [2 + 2] cycloaddition reaction and homogeneous Ziegler-Natta catalysis are investigated. Finally, a DFT modelling for the singlet-oxygen quenching ability and radical trapping activity of carotenes is presented. The simulated data provide a rationale for the protective action of carotenes observed in biological tissues and elucidates the physical and chemical mechanisms involved in the reactivity of carotenes versus oxygen and radicals.","PeriodicalId":20818,"journal":{"name":"Quantitative Structure-activity Relationships","volume":"27 1","pages":"128-148"},"PeriodicalIF":0.0,"publicationDate":"2002-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73030445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 21

Applications of density functional theory-based methods in medicinal chemistry 基于密度泛函理论的方法在药物化学中的应用

Quantitative Structure-activity Relationships Pub Date : 2002-07-01 DOI: 10.1002/1521-3838(200207)21:2<173::AID-QSAR173>3.0.CO;2-B

M. Sulpizi, G. Folkers, U. Rothlisberger, P. Carloni, L. Scapozza

{"title":"Applications of density functional theory-based methods in medicinal chemistry","authors":"M. Sulpizi, G. Folkers, U. Rothlisberger, P. Carloni, L. Scapozza","doi":"10.1002/1521-3838(200207)21:2<173::AID-QSAR173>3.0.CO;2-B","DOIUrl":"https://doi.org/10.1002/1521-3838(200207)21:2<173::AID-QSAR173>3.0.CO;2-B","url":null,"abstract":"With the advances in genomics, proteomics and functional genomics new therapeutic targets to be tackled by medicinal chemistry are expected. This article reviews applications of first principle methods to address medicinal chemistry issue related to drug/target interactions. Two selected representative case studies involving therapeutically interesting targets are presented. The first case study presents how DFT can contribute to ameliorate scoring functions for drug screening in particular by enabling the discrimination between inhibitors and substrates. The second example shows the use of DFT within the framework of a QM/MM mixed approach for elucidating mechanisms of reaction. This approach allows defining the electronic state and structure of the reaction transition state whose knowledge is essential for designing potent and specific transition state analogs inhibitors. Finally, addressing the issue of other medicinal chemistry related application of DFT we suggest that DFT has indeed the potentiality of becoming very important for challenging new issues presented to medicinal chemistry in the post genomic era.","PeriodicalId":20818,"journal":{"name":"Quantitative Structure-activity Relationships","volume":"3 1","pages":"173-181"},"PeriodicalIF":0.0,"publicationDate":"2002-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82028754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 35

Introduction to density-functional theory and ab-initio molecular dynamics 密度泛函理论及从头算分子动力学导论

Quantitative Structure-activity Relationships Pub Date : 2002-07-01 DOI: 10.1002/1521-3838(200207)21:2<97::AID-QSAR97>3.0.CO;2-6

R. Car

{"title":"Introduction to density-functional theory and ab-initio molecular dynamics","authors":"R. Car","doi":"10.1002/1521-3838(200207)21:2<97::AID-QSAR97>3.0.CO;2-6","DOIUrl":"https://doi.org/10.1002/1521-3838(200207)21:2<97::AID-QSAR97>3.0.CO;2-6","url":null,"abstract":"Density-Functional-Theory (DFT) provides a general framework to deal with the ground-state energy of the electrons in many-atom systems. Its history dates back to the work of Thomas [1], Fermi [2] and Dirac [3] who devised approximate expressions for the kinetic energy [1, 2] and the exchange energy [3] of many-electron systems in terms of simple functionals of the local electron density. These ideas were further elaborated in the Xα method of Slater [4], until finally, the foundations of the modern theory were laid down in the mid-sixties by Kohn and collaborators [5, 6]. Since then but particularly in the last two decades the number of applications of DFT to electronic structure problems has grown dramatically. Today DFT is the method of choice for first-principles electronic structure calculations in condensed phase and complex molecular environments. DFT based approaches are used in a variety of disciplines ranging from condensed matter physics, to chemistry, materials science, biochemistry and biophysics. There are several reason for this success: (i) DFT makes the many-body electronic problem tractable at a numerical cost of self-consistent-field single particle calculations; (ii) despite the severe approximations made to the exchange and correlation energy functional, DFT calculations are usually sufficiently accurate to predict materials structures or chemical reactions products; (iii) currently available computational power and modern numerical algorithms make DFT calculations feasible for realistic models of systems like e.g. an interface between two crystalline materials, a carbon nanotube, or the active site of an enzyme.","PeriodicalId":20818,"journal":{"name":"Quantitative Structure-activity Relationships","volume":"69 1","pages":"97-104"},"PeriodicalIF":0.0,"publicationDate":"2002-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72898754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 46

Density Functional Theory‐Based Molecular Dynamics of Biological Systems 基于密度泛函理论的生物系统分子动力学

Quantitative Structure-activity Relationships Pub Date : 2002-07-01 DOI: 10.1002/1521-3838(200207)21:2<166::AID-QSAR166>3.0.CO;2-3

P. Carloni

引用次数: 8

Computation of spectroscopic parameters in vacuo and in condensed phases by methods based on the density functional theory 用密度泛函理论计算真空和凝聚相的光谱参数

Quantitative Structure-activity Relationships Pub Date : 2002-07-01 DOI: 10.1002/1521-3838(200207)21:2<105::AID-QSAR105>3.0.CO;2-V

V. Barone, O. Crescenzi, R. Improta

引用次数: 17

Hybrid Car-Parrinello/molecular mechanics modelling of transition metal complexes: Structure, dynamics and reactivity 混合动力Car-Parrinello/过渡金属配合物的分子力学建模:结构、动力学和反应性

Quantitative Structure-activity Relationships Pub Date : 2002-07-01 DOI: 10.1002/1521-3838(200207)21:2<119::AID-QSAR119>3.0.CO;2-B

L. Guidoni, P. Maurer, S. Piana, U. Rothlisberger

{"title":"Hybrid Car-Parrinello/molecular mechanics modelling of transition metal complexes: Structure, dynamics and reactivity","authors":"L. Guidoni, P. Maurer, S. Piana, U. Rothlisberger","doi":"10.1002/1521-3838(200207)21:2<119::AID-QSAR119>3.0.CO;2-B","DOIUrl":"https://doi.org/10.1002/1521-3838(200207)21:2<119::AID-QSAR119>3.0.CO;2-B","url":null,"abstract":"The theoretical modelling of chemically active transition metal (TM) centres is a notoriously difficult task. The metal-ligand interactions in these complexes are often highly directional and the concoction of suitable analytic interaction potentials can be far from trivial. The situation is rendered even more difficult by the fact that at finite temperature, the system might switch dynamically between different bonding situations or exhibit several energetically close-lying spin states which are all characterized by different coordination numbers and geometries. In this article, we describe the structural, dynamical and reactive properties of complex TM-containing systems with the help of a mixed quantum mechanical/molecular mechanical (QM/MM) molecular dynamics approach, in which the TM centre is described with generalized gradient corrected density functional theory embedded in a classical force field description. The power of such a combined Car-Parrinello/molecular mechanics approach is illustrated with a number of representative examples ranging from enantioselective TM catalysts to radiopharmaceuticals and metalloenzymes.","PeriodicalId":20818,"journal":{"name":"Quantitative Structure-activity Relationships","volume":"8 1","pages":"119-127"},"PeriodicalIF":0.0,"publicationDate":"2002-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78575842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 11

NMR Study of Conformational Preferences of Inhibitors of Monoamine Uptake 单胺摄取抑制剂构象偏好的核磁共振研究

Quantitative Structure-activity Relationships Pub Date : 2002-05-01 DOI: 10.1002/1521-3838(200205)21:1<38::AID-QSAR38>3.0.CO;2-J

M. Appell, Aleksej Krunic, Tony Jeen Choi, S. Mariappan, W. Dunn, M. Reith

引用次数: 0

Fragmental Methods in the Design of New Compounds. Applications of The Advanced Algorithm Builder 新化合物设计中的片段化方法。高级算法生成器的应用

Quantitative Structure-activity Relationships Pub Date : 2002-05-01 DOI: 10.1002/1521-3838(200205)21:1<23::AID-QSAR23>3.0.CO;2-E

P. Japertas, R. Didziapetris, A. Petrauskas

引用次数: 60