Abstract:
:The treatment of neuropathic pain is very complex and there are few drugs approved for this purpose. Among the studied compounds in the literature, sigma-1 receptor antagonists have shown to be promising. In order to develop QSAR studies applied to the compounds of 1-arylpyrazole derivatives, multivariate analyses have been performed in this work using partial least square (PLS) and artificial neural network (ANN) methods. A PLS model has been obtained and validated with 45 compounds in the training set and 13 compounds in the test set (r2training = 0.761, q2 = 0.656, r2test = 0.746, MSEtest = 0.132 and MAEtest = 0.258). Additionally, multi-layer perceptron ANNs (MLP-ANNs) were employed in order to propose non-linear models trained by gradient descent with momentum backpropagation function. Based on MSEtest values, the best MLP-ANN models were combined in a MLP-ANN consensus model (MLP-ANN-CM; r2test = 0.824, MSEtest = 0.088 and MAEtest = 0.197). In the end, a general consensus model (GCM) has been obtained using PLS and MLP-ANN-CM models (r2test = 0.811, MSEtest = 0.100 and MAEtest = 0.218). Besides, the selected descriptors (GGI6, Mor23m, SRW06, H7m, MLOGP, and μ) revealed important features that should be considered when one is planning new compounds of the 1-arylpyrazole class. The multivariate models proposed in this work are definitely a powerful tool for the rational drug design of new compounds for neuropathic pain treatment. Graphical abstract Main scaffold of the 1-arylpyrazole derivatives and the selected descriptors.
journal_name
J Mol Modeljournal_title
Journal of molecular modelingauthors
Oliveira AA,Lipinski CF,Pereira EB,Honorio KM,Oliveira PR,Weber KC,Romero RAF,de Sousa AG,da Silva ABFdoi
10.1007/s00894-017-3444-3subject
Has Abstractpub_date
2017-10-02 00:00:00pages
302issue
10eissn
1610-2940issn
0948-5023pii
10.1007/s00894-017-3444-3journal_volume
23pub_type
杂志文章abstract::Faced with the worldwide spread of multidrug-resistant (MDR) bacterial strains, together with a lack of any appropriate treatment, urgent steps to combat infectious diseases should be taken. Usually, bacterial components are studied to understand, by analogy, the functioning of human proteins. However, molecular data ...
journal_title:Journal of molecular modeling
pub_type: 杂志文章
doi:10.1007/s00894-019-4073-9
更新日期:2019-06-11 00:00:00
abstract::In this work, the effect of the external electric field (EF) on the drug delivery performance of peptide-based metal-organic framework (MPF) for 6-mercaptopurine (6-MP) drug is investigated by means of the molecular dynamics (MD) simulations. It is found that the strength interaction of drug molecule with MPF is decre...
journal_title:Journal of molecular modeling
pub_type: 杂志文章
doi:10.1007/s00894-019-4178-1
更新日期:2019-09-06 00:00:00
abstract::Mechanisms for the activation of water, ammonia, and other small molecules by the PCcarbeneP nickel pincer complex were studied computationally with the aid of density functional theory. The calculation results indicate that the strongly donating, nucleophilic carbene center can engage in a variety of heterolytic spli...
journal_title:Journal of molecular modeling
pub_type: 杂志文章
doi:10.1007/s00894-015-2792-0
更新日期:2015-09-01 00:00:00
abstract::The deregulated breakpoint cluster region (Bcr)-Abelson tyrosine kinase (Abl) fusion protein represents an attractive pharmacological target for the treatment of chronic myeloid leukemia (CML). The high affinity of monobody AS25 was designed to target the Src homology 2 (SH2) domain of Bcr-Abl, leading to allosteric i...
journal_title:Journal of molecular modeling
pub_type: 杂志文章
doi:10.1007/s00894-017-3353-5
更新日期:2017-06-01 00:00:00
abstract::Thermodynamic integration (TI) molecular dynamics (MD) simulations for the binding of a pair of a reference ("ref") ligand and an analogous ("analog") ligand to either tagged (with six extra residues at the N-terminus) or untagged p38 kinase proteins were carried out in order to probe how the binding affinity is influ...
journal_title:Journal of molecular modeling
pub_type: 杂志文章
doi:10.1007/s00894-015-2825-8
更新日期:2015-11-01 00:00:00
abstract::Models of the hydrogenoxalate (bioxalate, charge -1) and oxalate (charge -2) anions were developed for classical molecular dynamics (CMD) simulations and parametrized against ab initio molecular dynamics (AIMD) data from our previous study (Kroutil et al. (2016) J Mol Model 22:210). The interactions of the anions with...
journal_title:Journal of molecular modeling
pub_type: 杂志文章
doi:10.1007/s00894-017-3490-x
更新日期:2017-10-28 00:00:00
abstract::Modulation of γ-aminobutyric acid (GABA) levels has been required in various disorders. GABA itself cannot be directly introduced into central nervous system (CNS) because of the blood brain barrier; inhibition of GABA aminotransferase (GABA-AT), which degrades GABA in CNS, has been the target for the modulation of GA...
journal_title:Journal of molecular modeling
pub_type: 杂志文章
doi:10.1007/s00894-020-04495-1
更新日期:2020-08-11 00:00:00
abstract::The formation of silaspiropentane from addition of singlet silacyclopropylidene 1 and silacyclopropylidenoid 8 to ethylene has been investigated separately at the B3LYP, X3LYP, WB97XD, and M05-2X theories using the 6-31+G(d,p) basis set. The silacycloproylidenoid addition follows a stepwise route. In contrast, a conce...
journal_title:Journal of molecular modeling
pub_type: 杂志文章
doi:10.1007/s00894-016-3016-y
更新日期:2016-07-01 00:00:00
abstract::The drug discovery process typically involves target identification and design of suitable drug molecules against these targets. Despite decades of experimental investigations in the drug discovery domain, about 96% overall failure rate has been recorded in drug development due to the "undruggability" of various ident...
journal_title:Journal of molecular modeling
pub_type: 杂志文章,评审
doi:10.1007/s00894-020-04385-6
更新日期:2020-05-08 00:00:00
abstract::We investigated the dynamics of an electron subjected to a uniform electric field in the scope of a tight-binding electron-phonon interacting approach. We aimed at describing the transport in a one-dimensional lattice in which the on-site energies are distributed according to a Fibonacci sequence. Within this physical...
journal_title:Journal of molecular modeling
pub_type: 杂志文章
doi:10.1007/s00894-019-3972-0
更新日期:2019-03-28 00:00:00
abstract::The geometries, relative stabilities of some 4(7) and 5(6) substituted 2-hydroxybenzimidazole derivatives were calculated with full geometry optimization using AM1 and PM3 in aqueous phase. With the exception of molecules 4, 6 and 7 for all the 4(7) and 5(6) substituted 2-hydroxybenzimidazole derivatives the 3H and ke...
journal_title:Journal of molecular modeling
pub_type: 杂志文章
doi:10.1007/s00894-003-0150-0
更新日期:2003-12-01 00:00:00
abstract::A detailed study of the structural, electronic, and optical absorption properties of crystalline 1,4-dinitrofurazano[3,4-b]piperazine (DNFP) under hydrostatic pressures of 0-100 GPa was performed using periodic density functional theory. As the pressure increases, the lattice constants and cell volumes calculated by L...
journal_title:Journal of molecular modeling
pub_type: 杂志文章
doi:10.1007/s00894-012-1547-4
更新日期:2013-01-01 00:00:00
abstract::The pathogen Legionella longbeachae is a causative agent of legionellosis. The antibiotic resistance is the major problem of this modern world. Thus, selective pressure warrants the need for identification of newer drug target. In current study, subtractive proteomics approach screen out SIS (sugar isomerase) domain p...
journal_title:Journal of molecular modeling
pub_type: 杂志文章
doi:10.1007/s00894-020-04475-5
更新日期:2020-08-03 00:00:00
abstract::Two uridine 2',3'-cyclic monophosphate (cUMP) derivatives, 5'-deoxy (DcUMP) and 5'-O-methyl (McUMP), were studied by means of quantum chemical methods. Aqueous solvent effects were estimated based on the isodensity-surface polarized-continuum model (IPCM). Gas phase calculations revealed only slight energy differences...
journal_title:Journal of molecular modeling
pub_type: 杂志文章
doi:10.1007/s00894-005-0019-5
更新日期:2006-01-01 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::The ternary complexes ML∙∙∙PyZX2∙∙∙NH3 (ML = CuCl, CuCN, AgCN, and AuCN; Z = P, As, and Sb; X = H and F) have been investigated with quantum chemical calculations. The results showed that the existence of coordination interaction has a prominent enhancing effect on the strength of pnicogen bonding. Even in ML∙∙∙PySbH2...
journal_title:Journal of molecular modeling
pub_type: 杂志文章
doi:10.1007/s00894-016-2929-9
更新日期:2016-03-01 00:00:00
abstract::Reactions of lithium halide (LiX, X = F, Cl, Br and I) and methyl halide (CH₃X, X = F, Cl, Br and I) have been investigated at the B3LYP/6-31G(d) level of theory using the microhydration model. Beginning with hydrated lithium ion, four or two water molecules have been conveniently introduced to these aqueous-phase hal...
journal_title:Journal of molecular modeling
pub_type: 杂志文章
doi:10.1007/s00894-010-0688-6
更新日期:2010-12-01 00:00:00
abstract::Colorectal cancer, which is considered one of the leading causes of mortality worldwide, develops through the formation of benign polyps on the inner colon or rectum wall. Truncations in adenomatous polyposis coli (APC) gene lead to the spread of the disease in the entire colon region when combined with the guanine nu...
journal_title:Journal of molecular modeling
pub_type: 杂志文章
doi:10.1007/s00894-020-04467-5
更新日期:2020-07-16 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::Meta-hybrid density functional theory calculations using M06-2X/6-31+G(d,p) and M06-2X/6-311+G(d,p) levels of theory have been performed to understand the strength of C-H(…)π interactions of two possible types for benzene-acetylene, 1,3,5-trifluorobenzene-acetylene and coronene-acetylene complexes. Our study reveals t...
journal_title:Journal of molecular modeling
pub_type: 杂志文章
doi:10.1007/s00894-012-1729-0
更新日期:2013-07-01 00:00:00
abstract::This paper used numerical and experimental methods to investigate the mechanical properties of amorphous NiAl alloys during the nanoindentation process. A simulation was performed using the many-body tight-binding potential method. Temperature, plastic deformation, elastic recovery, and hardness were evaluated. The ex...
journal_title:Journal of molecular modeling
pub_type: 杂志文章
doi:10.1007/s00894-015-2714-1
更新日期:2015-06-01 00:00:00
abstract::Recent ab initio investigations of some complexes formed between carbon dioxide and its analogues carbonyl sulfide, carbonyl selenide, carbon disulfide, and thiocarbonyl selenide and the common bases ammonia, water, phosphine, and hydrogen sulfide have revealed significant differences between the properties of those c...
journal_title:Journal of molecular modeling
pub_type: 杂志文章
doi:10.1007/s00894-014-2562-4
更新日期:2015-02-01 00:00:00
abstract::The role of resultant gradient-information concept, reflecting the kinetic energy of electrons, in shaping the molecular electronic structure and reactivity preferences of open reactants is examined. This quantum-information descriptor combines contributions due to both the modulus (probability) and phase (current) co...
journal_title:Journal of molecular modeling
pub_type: 杂志文章
doi:10.1007/s00894-019-4028-1
更新日期:2019-08-16 00:00:00
abstract::It is well-known that properties of poly(vinyl alcohol) (PVA) in the pure and solution states depend largely on the hydrogen bonding networks formed. In the context of molecular simulation, such networks are handled through the Coulombic interactions. Therefore, a good set of partial atom charges (PACs) for simulation...
journal_title:Journal of molecular modeling
pub_type: 杂志文章
doi:10.1007/s00894-014-2554-4
更新日期:2015-03-01 00:00:00
abstract::Amorphous molecular simulation to model the reaction species in the synthesis of chemically inert and energetic 1,1-diamino-2,2-dinitroethene (DADNE) explosive material was performed in this work. Nitromethane was selected as the starting reactant to undergo halogenation, nitration, deprotonation, intermolecular conde...
journal_title:Journal of molecular modeling
pub_type: 杂志文章
doi:10.1007/s00894-016-3182-y
更新日期:2017-01-01 00:00:00
abstract::The cold shock protein from the hyperthermophile Thermotoga maritima (Tm-Csp) exhibits significantly higher thermostability than its homologue from the thermophile Bacillus caldolyticus (Bc-Csp). Experimental studies have shown that the electrostatic interactions unique to Tm-Csp are responsible for improving its ther...
journal_title:Journal of molecular modeling
pub_type: 杂志文章
doi:10.1007/s00894-016-2958-4
更新日期:2016-04-01 00:00:00
abstract::Ten functionals were used to assess their capability to compute a local reactivity descriptor coming from the Conceptual Density Functional Theory on a group of iron-based organometallic compounds that have been synthesized by Zohuri, G.H. et al. in 2010; these compounds bear the following substituent groups: H-, O2N-...
journal_title:Journal of molecular modeling
pub_type: 杂志文章
doi:10.1007/s00894-017-3576-5
更新日期:2018-01-18 00:00:00
abstract::The effect of terminal GLY114* deletion on the binding affinity of the PA-IIL lectin toward L: -fucose was investigated. Both experimental (isothermal titration calorimetry) and computational (molecular dynamics simulations) methods have shown that the deletion mutation decreases the L-fucose affinity. It implies that...
journal_title:Journal of molecular modeling
pub_type: 杂志文章
doi:10.1007/s00894-009-0464-7
更新日期:2009-06-01 00:00:00
abstract::Cyclic nucleotide binding domain (CNBD) is a ubiquitous domain of effector proteins involved in signalling cascades of prokaryota and eukaryota. CNBD activation by cyclic nucleotide monophosphate (cNMP) is studied well in the case of several proteins. However, this knowledge is hardly applicable to cNMP-modulated cati...
journal_title:Journal of molecular modeling
pub_type: 杂志文章
doi:10.1007/s00894-012-1404-5
更新日期:2012-09-01 00:00:00
abstract::The crystal structure of the human cystatin C (hCC) dimer revealed that a stable twofold-symmetric dimer was formed via 3D domain swapping. Domain swapping with the need for near-complete unfolding has been proposed as a possible route for amyloid fibril initiation. Thus, the interesting interactions that occur betwee...
journal_title:Journal of molecular modeling
pub_type: 杂志文章
doi:10.1007/s00894-012-1609-7
更新日期:2013-02-01 00:00:00