Abstract:
:Different forms of synaptic plasticity in the cerebellum expressed at the synapses onto Purkinje cells (PCs) are mediated by membrane metabotropic glutamate receptors (mGluRs). There are three main mGluR groups with a total of 8 subtypes. Although mGluRs are also found at the climbing fiber (CF) to PC synapses, the distribution and biological activity of their types is not well-known. Using whole cell patch-clamp recordings from PCs in rat cerebellar slices with inhibitors of ionotropic receptors and glutamate uptake blockers we demonstrate a complex pharmacology of currents obtained by CF stimulation. The mGluR1 specific antagonist CPCCOEt in a group of cells suppressed this response, but in a similar number of other cells it induced a potentiating effect. It was found that a switch between these two biopharmaceutical effects might occur with age.
journal_name
J Chem Inf Modeljournal_title
Journal of chemical information and modelingauthors
Andjus PR,Bajić A,Zhu L,Strata Pdoi
10.1021/ci050161skeywords:
subject
Has Abstractpub_date
2005-11-01 00:00:00pages
1536-8issue
6eissn
1549-9596issn
1549-960Xjournal_volume
45pub_type
杂志文章abstract::Databases of small, potentially bioactive molecules are ubiquitous across the industry and academia. Designed such that each unique compound should appear only once, the multiplicity of ways in which many compounds can be represented means that these databases require methods for standardizing the representation of ch...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.0c00232
更新日期:2020-08-24 00:00:00
abstract::MHC class II molecules bind peptides derived from extracellular proteins that have been ingested by antigen-presenting cells and display them to the immune system. Peptide loading occurs within the antigen-presenting cell and is facilitated by HLA-DM. HLA-DM stabilizes the open conformation of the MHCII binding groove...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.9b00104
更新日期:2019-06-24 00:00:00
abstract::Binding affinity prediction with implicit solvent models remains a challenge in virtual screening for drug discovery. In order to assess the predictive power of implicit solvent models in docking techniques with Amber scoring, three generalized Born models (GBHCT, GBOBCI, and GBOBCII) available in Dock 6.7 were utiliz...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.6b00418
更新日期:2016-10-24 00:00:00
abstract::Traditional herbal medicine has been an inseparable part of the traditional medical science in many countries throughout history. Nowadays, the popularity of using herbal medicines in daily life, as well as clinical practices, has gradually expanded to numerous Western countries with positive impacts and acceptance. T...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.9b00826
更新日期:2020-03-23 00:00:00
abstract::Antimicrobial peptides (AMPs) have emerged as promising therapeutic alternatives to fight against the diverse infections caused by different pathogenic microorganisms. In this context, theoretical approaches in bioinformatics have paved the way toward the creation of several in silico models capable of predicting anti...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.5b00630
更新日期:2016-03-28 00:00:00
abstract::Physicochemical properties of compounds have been instrumental in selecting lead compounds with increased drug-likeness. However, the relationship between physicochemical properties of constituent drugs and the tendency to exhibit drug interaction has not been systematically studied. We assembled physicochemical descr...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci500276x
更新日期:2014-08-25 00:00:00
abstract::Simulating protein flexibility is a major issue in the docking-based drug-design process for which a single methodological solution does not exist. In our search of new anti-Alzheimer ligands, we were faced with the challenge of including receptor plasticity in a virtual screening campaign aimed at finding new β-secre...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci300390h
更新日期:2012-10-22 00:00:00
abstract::The Common Instrument Middleware Architecture (CIMA) aims at Grid-enabling a wide range of scientific instruments and sensors to enable easy access to and sharing and storage of data produced by these instruments and sensors. This paper describes the implementation of CIMA applied to the field of single-crystal X-ray ...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci050368l
更新日期:2006-05-01 00:00:00
abstract::Reduction of the affinity of the fragment crystallizable (Fc) region with immune receptors by substitution of one or a few amino acids, known as Fc-silencing, is an established approach to reduce the immune effector functions of monoclonal antibody therapeutics. This approach to Fc-silencing, however, is problematic a...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.9b01198
更新日期:2020-11-23 00:00:00
abstract::The membrane permeability of cyclic peptides and peptidomimetics, which are generally larger and more complex than typical drug molecules, is likely strongly influenced by the conformational behavior of these compounds in polar and apolar environments. The size and complexity of peptides often limit their bioavailabil...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.6b00251
更新日期:2016-08-22 00:00:00
abstract::Generalization of an earlier algorithm has led to the development of new local structural alignment algorithms for prediction of protein-protein binding sites. The algorithms use maximum cliques on protein graphs to define structurally similar protein regions. The search for structural neighbors in the new algorithms ...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci100265x
更新日期:2010-10-25 00:00:00
abstract::Cytochrome P450 2D6 (CYP2D6) is used to develop an approach for predicting affinity and relevant binding conformation(s) for highly flexible binding sites. The approach combines the use of docking scores and compound properties as attributes in building a neural network (NN) model. It begins by identifying segments of...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci600267k
更新日期:2006-11-01 00:00:00
abstract::The human DNA-repair O (6)-alkylguanine DNA alkyltransferase (MGMT or hAGT) protein protects DNA from environmental alkylating agents and also plays an important role in tumor resistance to chemotherapy treatment. Available inhibitors, based on pseudosubstrate analogs, have been shown to induce substantial bone marrow...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci700447r
更新日期:2008-04-01 00:00:00
abstract::We introduce TICRA (transplant-insert-constrain-relax-assemble), a method for modeling the structure of unknown protein-ligand complexes using the X-ray crystal structures of homologous proteins and ligands with known activity. We present results from modeling the structures of protein kinase-inhibitor complexes using...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci100256u
更新日期:2011-01-24 00:00:00
abstract::The possibility of improving the predictive ability of comparative molecular field analysis (CoMFA) by settings optimization has been evaluated to show that CoMFA predictive ability can be improved. Ten different CoMFA settings are evaluated, producing a total of 6120 models. This method has been applied to nine diffe...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci049612j
更新日期:2006-01-01 00:00:00
abstract::The more that is known about human and other genome sequences and the correlation between gene expression and the course of a disease, the more evident it seems to be that DNA is chosen as a drug target instead of proteins which are built with the information encoded by DNA. According to this approach, small minor gro...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci600500v
更新日期:2007-07-01 00:00:00
abstract::Compounds with high-confidence target annotations and activity measurements in the original and current release of the ChEMBL database have been compared to better understand how the growth of compound activity data might influence the spectrum of ligand-target interactions and the degree of target promiscuity among a...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci3003304
更新日期:2012-10-22 00:00:00
abstract::Virtual screening of small molecules against a protein target often identifies the correct pose, but the ranking in terms of binding energy remains a difficult problem, resulting in unacceptable numbers of false positives and negatives. To investigate this problem, the performance of three docking programs, FRED, QXP/...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci800154w
更新日期:2008-10-01 00:00:00
abstract::Encapsulation of peptide and protein-based drugs in polymeric nanoparticles is one of the fundamental fields in controlled-release drug delivery systems. The molecular mechanisms of absorption of peptides to the polymeric nanoparticles are still unknown, and there is no precise molecular data on the encapsulation proc...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.8b00641
更新日期:2019-01-28 00:00:00
abstract::Histone deacetylases (HDACs) are an important class of drug targets for the treatment of cancers, neurodegenerative diseases, and other types of diseases. Virtual screening (VS) has become fairly effective approaches for drug discovery of novel and highly selective histone deacetylase inhibitors (HDACIs). To facilitat...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci5005515
更新日期:2015-02-23 00:00:00
abstract::The protection exerted by 3,5-dihydroxy-4-methoxybenzyl alcohol (DHMBA), a phenolic compound recently isolated from the Pacific oyster, against oxidative stress (OS) is investigated using the density functional theory. Our results indicate that DHMBA is an outstanding peroxyl radical scavenger, being about 15 times an...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.5b00513
更新日期:2015-12-28 00:00:00
abstract::The community structure-activity resource (CSAR) data sets are used to develop and test a support vector machine-based scoring function in regression mode (SVR). Two scoring functions (SVR-KB and SVR-EP) are derived with the objective of reproducing the trend of the experimental binding affinities provided within the ...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci200078f
更新日期:2011-09-26 00:00:00
abstract::The early stages of drug discovery rely on hit-to-lead programs, where initial hits undergo partial optimization to improve binding affinities for their biological target. This is an expensive and time-consuming process, requiring multiple iterations of trial and error designs, an ideal scenario for applying computer ...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.9b00938
更新日期:2020-03-23 00:00:00
abstract::Selecting a small subset of descriptors from a large pool to build a predictive quantitative structure-activity relationship (QSAR) model is an important step in the QSAR modeling process. In general, subset selection is very hard to solve, even approximately, with guaranteed performance bounds. Traditional approaches...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci600563w
更新日期:2007-05-01 00:00:00
abstract::The number of journal articles in the scientific domain has grown to the point where it has become impossible for researchers to capitalize on all findings in their relevant discipline. Information is stored in these articles in a number of ways, including figures that describe important results. In organic chemistry,...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.0c00042
更新日期:2020-04-27 00:00:00
abstract::Homology modeling is a reliable method of predicting the three-dimensional structures of proteins that lack NMR or X-ray crystallographic data. It employs the assumption that a structural resemblance exists between closely related proteins. Despite the availability of many crystal structures of possible templates, onl...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci500001f
更新日期:2014-06-23 00:00:00
abstract::This paper presents an exploratory study of a novel method for flexible 3-D similarity searching based on autocorrelation vectors and smoothed bounded distance matrices. Although the new approach is unable to outperform an existing 2-D similarity searching in terms of enrichment factors, it is able to retrieve differe...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci0503863
更新日期:2006-03-01 00:00:00
abstract::Nonalcoholic hepatic steatosis is a worldwide epidemiological concern since it is among the most prominent hepatic diseases. Indeed, research in toxicology and epidemiology has gathered evidence that exposure to endocrine disruptors can perturb cellular homeostasis and cause this disease. Therefore, assessing the like...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.8b00297
更新日期:2018-08-27 00:00:00
abstract::The determination of the validity of a QSAR model when applied to new compounds is an important concern in the field of QSAR and QSPR modeling. Various scoring techniques can be applied to specific types of models. We present a technique with which we can state whether a new compound will be well predicted by a previo...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci0497511
更新日期:2005-01-01 00:00:00
abstract::Designing organic saccharide sensors for use in aqueous solution is a nontrivial endeavor. Incorporation of hydrogen bonding groups on a sensor's receptor unit to target saccharides is an obvious strategy but not one that is likely to ensure analyte-receptor interactions over analyte-solvent or receptor-solvent intera...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.8b00987
更新日期:2019-05-28 00:00:00