Abstract：
:Cyclooxygenase (COX) enzymes catalyse the biosynthesis of prostaglandins and thromboxane from arachidonic acid (AA). We summarize in this paper, the development of pharmacophores of a dataset of inhibitors for COX-2 by using the Catalyst/Hypogen module using six chemically diverse series of compounds. Training set consisting of 24 compounds was carefully selected. The activity spread of the training set molecules was from 0.1 to 10000 nM. The most predictive pharmacophore model (hypothesis 1), consisting of four features, namely, one hydrogen bond donor, one hydrogen bond acceptor, one hydrophobic aliphatic and one ring aromatic feature, had a correlation (r) of 0.954 and a root mean square deviation of 0.894. The entropy (configuration cost) value of the hypotheses was 16.79, within the allowed range. The difference between the null hypothesis and the fixed cost and between the null hypothesis and the total cost of the best hypothesis (hypothesis 1) was 88.37 and 78.51, respectively. The model was validated on a test set consisting of six different series of structurally diverse 22 compounds and performed well in classifying active and inactive molecules correctly. This validation approach provides confidence in the utility of the predictive pharmacophore model developed in this work as a 3D query tool in the virtual screening of drug like molecules to retrieve new chemical entities as potent COX-2 inhibitors. The model can also be used to predict the biological activities of compounds prior to their costly and time-consuming synthesis.
journal_name
J Mol Modeljournal_title
Journal of molecular modelingauthors
Chopra M,Gupta R,Gupta S,Saluja Ddoi
10.1007/s00894-008-0350-8subject
Has Abstractpub_date
2008-11-01 00:00:00pages
1087-99issue
11eissn
1610-2940issn
0948-5023journal_volume
14pub_type
杂志文章abstract：:Ethanol and water are the solvents most commonly used to extract flavonoids from propolis. Do hydrogen-bonding interactions exist between flavonoids and ethanol/water? In this work, this question was addressed by using density functional theory (DFT) to provide information on the hydrogen-bonding interactions between ...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-016-2968-2
更新日期：2016-04-01 00:00:00
abstract：:Using ligand and receptor based virtual screening approaches we have identified potential virtual screening hits targeting type II dehydroquinase from Mycobacterium tuberculosis, an effective and validated anti-mycobacterial target. Initially, we applied a virtual screening workflow based on a combination of 2D struct...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-009-0595-x
更新日期：2010-04-01 00:00:00
abstract：:Three potential anticancer agents {trans-[PtCl(2)(NH(3))(thiazole)], cis-[PtCl(2)(NH(3))(piperidine)], and PtCl(2)(NH(3))(cyclohexylamine) (JM118)} were explored and compared with cisplatin and the inactive [PtCl(dien)](+) complex. Basic electronic properties, bonding and stabilization energies were determined, and th...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-008-0285-0
更新日期：2008-08-01 00:00:00
abstract：:The complexes formed between TX3-ZX2 (T = C, Si, Ge; Z = P, As, Sb; X = F, Cl) and NH3 were studied at the MP2/aug-cc-pVTZ(PP) level. For each TX3-ZX2, two types of complex were obtained. For CX3-ZX2, NH3 is inclined to approach the σ-hole on the Z atom, forming a pnicogen bond. For TX3-ZX2 (T = Si and Ge), however, t...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-018-3732-6
更新日期：2018-08-20 00:00:00
abstract：:NBO-NJC decomposition of vicinal (3)J HH spin-spin coupling constants into Lewis, delocalization, and repolarization contributions are presented. A deep study allows to assign the main contributions to specific orbitals or electron delocalizations between two orbitals. (3)J HH torsional dependence and the substituent ...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-014-2225-5
更新日期：2014-07-01 00:00:00
abstract：:Molecular modeling of the La(III) complex of 3,3'-(benzylidene)bis(4-hydroxycoumarin) (PhDC) was performed using density functional theory (DFT) methods at B3LYP/6-31G(d) and BP86/TZP levels. Both Stuttgart-Dresden effective core potential and ZORA approximation were applied to the La(III) center. The electron density...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-008-0277-0
更新日期：2008-05-01 00:00:00
abstract：:The present study reports the geometry, electronic structure and properties of neutral and anionic transition metal (TM = Ti, Zr and Hf)) doped germanium clusters containing 1 to 20 germanium atoms within the framework of linear combination of atomic orbitals density functional theory under spin polarized generalized ...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-011-1122-4
更新日期：2012-01-01 00:00:00
abstract：:The structural characteristics involving thermal stabilities of liquid nitromethane (NM)—one of the simplest energetic materials—confined within a graphene (GRA) bilayer were investigated by means of all-atom molecular dynamics simulations and density functional theory calculations. The results show that ordered and l...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-015-2588-2
更新日期：2015-03-01 00:00:00
abstract：:A series of oligo(thienylenevinylene) derivatives with 1,4-dihydropyrrolo[3,2-b]pyrrole as core has been investigated at the PBE0/6-31G(d) and the TD-PBE0/6-31+G(d,p) levels to design materials with high performances such as broad absorption spectra and higher balance transfer property. The results show that position ...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-013-1920-y
更新日期：2013-09-01 00:00:00
abstract：:To determine the kinase inhibitory potential of natural products that could be utilized in lung cancer therapy in the near future, a pharmacophore-based activity profiling protocol using parallel pharmacophore-based virtual screening of ZINC-a natural product database-was employed. The work presented here is based on ...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-018-3849-7
更新日期：2018-10-20 00:00:00
abstract：:3-phosphoinositide-dependent protein kinase-1 (PDK1) plays a crucial role in the signal transduction of massive growth-related protein kinases. In this work, a computational study has been performed to investigate the binding pose of the hydrolyzed product of SBF1 (SBF1-) with PDK1. The binding pose was predicted by V...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-019-4069-5
更新日期：2019-06-13 00:00:00
abstract：:Hydrogenoxalate (charge -1) and oxalate (charge -2) anions and their solvated forms were studied by various computational techniques. Ab initio quantum chemical calculations in gas phase, in implicit solvent and microsolvated (up to 32 water molecules) environment were performed in order to explore a potential energy ...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-016-3075-0
更新日期：2016-09-01 00:00:00
abstract：:The geometries, stabilities, and electronic properties of ScBn (n = 1-12) clusters have been systematically investigated by using density functional theory B3LYP method and coupled-cluster theory CCSD(T) method. It is found that the ground state isomers of ScBn have planar or quasi-planar structure when n ≤ 6, which c...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-013-1860-6
更新日期：2013-08-01 00:00:00
abstract：:Very recently, an unprecedented novel monometallic cluster of fullerenes entrapping a yttrium cyanide (YCN) cluster inside a popular C82 cage YCN@Cs(6)-C82 was synthesized and characterized. Inspired by this investigation, four non-IPR YCN@C1(17459)-C76, YCN@C2v(19138)-C76, YCN@C2(17646)-C76, and YCN@C1(17894)-C76 (1,...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-016-3040-y
更新日期：2016-08-01 00:00:00
abstract：:The mechanism and origin of selectivity for [3 + 2]-cycloaddition (32CA) reactions between thioketone and carbohydrate-derived nitrones in THF were investigated by using the density functional theory (DFT) at the M06-2X/6-311+G(d,p)//M06-2X/6-31+G(d,p) level of theory combined with the solvation SMD model. The calcula...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-019-4104-6
更新日期：2019-07-02 00:00:00
abstract：:The USFDA has approved pramlintide, commercially named Symlin (sIAPP), as adjunctive therapy for type 2 diabetes (T2D). This analogue of the human amylin peptide (hIAPP) has triple proline substitutions typical of the rat isoform (rIAPP). Recently, it was proposed that pramlintide solubility and aggregation resistance...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-019-4137-x
更新日期：2019-08-19 00:00:00
abstract：:Molecular simulations were carried out to study the sodium dodecyl sulfate (SDS) surfactant with the interleukin 8 (IL8) protein as a model to investigate the influence of amphiphilic molecules on proteins. Simulations for an SDS micelle with an IL8 protein show that both aggregates, which were initially separated, ev...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-017-3386-9
更新日期：2017-07-01 00:00:00
abstract：:The biological toxicity of uranyl ion (UO (2) (2+) ) lies in interacting with proteins and disrupting their native functions. The structural and functional consequences of UO (2) (2+) interacting with cytochrome b (5) (cyt b (5)), a small membrane heme protein, and its heme axial ligand His39Ser variant, cyt b (5) H39...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-011-1097-1
更新日期：2012-03-01 00:00:00
abstract：:The interpretation of mass spectra (ms) of molecules containing poly-isotopic elements (e.g. Ge, Se, W, Os, Sn, Te, Zn, Yb) can be difficult due to the occurrence of fragments resulting from isotopomeric composition. MS-clusters located in the range lower than or equal to M/2 are very difficult to interpret. In this a...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-009-0486-1
更新日期：2009-06-01 00:00:00
abstract：:Cathepsin S has been demonstrated to play a crucial role in the remodeling of extracellular matrix proteins such as elastin and collagen, which in turn contribute to the structural integrity of the cardiovascular wall. Atherosclerotic lesions, aneurysm formation, plaque rupture, thrombosis, and calcification are some ...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-017-3255-6
更新日期：2017-03-01 00:00:00
abstract：:Density functional theory (DFT) was used to investigate cobalt(0)-catalyzed intramolecular hydroacylation of 4-pentenal. The calculated results indicated the involvement of five possible reaction pathways: the formation of cyclopentanone, cyclobutanone, butylenes, cyclobutane, and cyclopropane, respectively. The forme...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-013-1772-5
更新日期：2013-06-01 00:00:00
abstract：:The Grand Canonical Monte Carlo method was used to analyse the phenomenon of adsorption of aromatic compounds (i.e. phenol, toluene, benzoic acid and salicylic acid) on the surface of the titania-silica (TiO2/SiO2) catalyst. We found that different types of interactions play important roles in the adsorption of molecu...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-007-0189-4
更新日期：2007-07-01 00:00:00
abstract：:G-Quadruplex and i-Motif-forming sequences in the promoter regions of several oncogenes show promise as targets for the regulation of oncogenes. In this study, molecular models were created for the c-MYC NHE-III(1) (nuclease hypersensitivity element III(1)) from two 39-base complementary sequences. The NHE modeled her...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-007-0254-z
更新日期：2008-02-01 00:00:00
abstract：:The geometric and electronic structure of tetracyanoethylene (TCNE)-aniline (donor-acceptor type) complex has been investigated in gas phase using ab initio and time dependent density functional theory calculations. Both the above calculations predict a composed structure for the complex, in which the interacting site...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-008-0443-4
更新日期：2009-08-01 00:00:00
abstract：:The mechanism of the copper(I)-catalyzed cyclopropanation reaction for methyl diazoacetate with both (Z)- and (E)-but-2-ene stereoisomers has been studied using the 6-311++G(d,p) basis set by means of M06-2X and O3LYP functionals. According to both methods, the rate-limiting step is the formation of a copper-carbene i...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-018-3737-1
更新日期：2018-07-05 00:00:00
abstract：:The formation of selenium species in some biological processes involves the generation of ionic and radical intermediates such as RSe●, RSe-, RSeO●, and RSeO-, among others. We performed a theoretical study of the possible mechanisms for the reaction of the two simplest Se radicals-the hydroselenyl (HSe●) and seleneni...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-017-3535-1
更新日期：2017-12-05 00:00:00
abstract：:Multiple receptors conformation docking (MRCD) and clustering of dock poses allows seamless incorporation of receptor binding conformation of the molecules on wide range of ligands with varied structural scaffold. The accuracy of the approach was tested on a set of 120 cyclic urea molecules having HIV-1 protease inhib...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-011-1048-x
更新日期：2012-02-01 00:00:00
abstract：:This theoretical study presents a comparative analysis of the molecular properties of heterocyclic (C2H4O...HF and C2H5...HF) and homocyclic (C3H6...HF) hydrogen-bonded complexes. Initially, the equilibrium geometries of these complexes were analyzed in detail at the B3LYP/6-311++G(d,p) level of theory. Subsequently, ...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-008-0380-2
更新日期：2009-02-01 00:00:00
abstract：:The effects of L-serine amino acid functionalization on a graphene plane were investigated through density functional theory calculations compared with those of oxygen functionalization. Three systems of 4 × 4 graphene supercells were created and functionalized by an epoxy group, a hydroxyl group, and an L-serine mole...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-020-04466-6
更新日期：2020-07-13 00:00:00
abstract：:The efficiency and high specificity of tobacco etch virus protease (TEVp) has made it widely used for cleavage of recombinant fusion proteins. However, TEVp suffers from a few intrinsic defects such as self-cleavage, poorly expressed in E. coli and less soluble. So some mutants were designed to improve it, such as S21...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-013-1930-9
更新日期：2013-11-01 00:00:00
