Abstract：
:3-Pyridyl ethers are excellent nAChRs ligands, which show high subtype selectivity and binding affinity to alpha4beta2 nAChR. Although the quantitative structure-activity relationship (QSAR) of nAChRs ligands has been widely investigated using various classes of compounds, the open ring analogues of 3-pyridyl ethers have been less involved in these studies due to the greater flexibility of this kind of molecule. In this study, two three-dimensional QSAR techniques and one two-dimensional QSAR technique were used to correlate the molecular structure with the biological activity of 64 analogues of 3-pyridyl ethers. Three different QSAR models were established. Their performances in the QSAR studies of open ring analogues of 3-pyridyl ethers were evaluated by the statistical values in the corresponding models. All models exhibited satisfactory predictive power. Of these models, the HQSAR behaved optimally in terms of the statistical values with q2=0.845, r2=0.897. Finally, graphic interpretation of three different models provided coincident information about the interaction of the ligand-receptor complex and supplied useful guidelines for the synthesis of novel, potent ligands.
journal_name
J Chem Inf Modeljournal_title
Journal of chemical information and modelingauthors
Zhang H,Li H,Liu Cdoi
10.1021/ci0498113keywords:
subject
Has Abstractpub_date
2005-03-01 00:00:00pages
440-8issue
2eissn
1549-9596issn
1549-960Xjournal_volume
45pub_type
杂志文章abstract：:We have performed a ligand coordinate analysis to monitor the movement of the inhibitor SC-558 from the active site of the COX-2 protein to the exterior using molecular dynamics techniques. This study provides an insight into the intermolecular interactions formed by the ligand during this journey. The published cryst...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci050142i
更新日期：2006-07-01 00:00:00
abstract：:Growing data sets with increased time for analysis is hampering predictive modeling in drug discovery. Model building can be carried out on high-performance computer clusters, but these can be expensive to purchase and maintain. We have evaluated ligand-based modeling on cloud computing resources where computations ar...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci500580y
更新日期：2015-01-26 00:00:00
abstract：:Cyanobacterial fructose-1,6-/sedoheptulose-1,7-bisphoshatase (cy-FBP/SBPase) is a potential enzymatic target for screening of novel inhibitors that can combat harmful algal blooms. In the present study, we targeted the substrate binding pocket of cy-FBP/SBPase. A series of novel hit compounds from the SPECs database w...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci4007529
更新日期：2014-03-24 00:00:00
abstract：:Computational approaches to fragment-based drug design (FBDD) can complement experiments and facilitate the identification of potential hot spots along the protein surface. However, the evaluation of computational methods for mapping binding sites frequently focuses upon the ability to reproduce crystallographic coord...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci300430v
更新日期：2013-02-25 00:00:00
abstract：:With chemical libraries increasingly containing millions of compounds or more, there is a fast-growing need for computational methods that can rank or prioritize compounds for screening. Machine learning methods have shown considerable promise for this task; indeed, classification methods such as support vector machin...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci9003865
更新日期：2010-05-24 00:00:00
abstract：:With a rapid increase in the number of high-resolution protein-ligand structures, the known protein-ligand structures can be used to gain insight into ligand-binding modes in a target protein. On the basis of the fact that the structurally similar binding sites share information about their ligands, we have developed ...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci300178e
更新日期：2012-10-22 00:00:00
abstract：:Functional diversity of the three-finger-protein domain (TFPD) had been acquired via hypervariability of some sequence positions and extensive insertion/deletion of short AA-segments that caused multidimensional drift of several sequence attributes such as the overall (HI) and local hydrophobicity levels, the isoelect...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.5b00322
更新日期：2015-09-28 00:00:00
abstract：:Protein-polysaccharide complexes constructed via self-assembly methods are often used to develop novel biomaterials for a wide range of applications in biomedicine, food, and biotechnology. The objective of this work was to investigate theoretically and to demonstrate via constant-pH Monte Carlo simulations that the c...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.9b00814
更新日期：2020-02-24 00:00:00
abstract：:Flavonoids, the vastest class of natural polyphenols, are extensively investigated for their multiple benefits on human health. Due to their physicochemical or biological properties, many representatives are considered to exhibit low selectivity among various protein targets or to plague high-throughput screening (HTS...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci5002668
更新日期：2014-08-25 00:00:00
abstract：:Calcium and magnesium ions play important roles in many physicochemical processes. To facilitate the investigation of phenomena related to these ions that occur over large length and time scales, a coarse-grained force field (CGFF) is developed for MgCl2 and CaCl2 aqueous solutions. The ions are modeled by CG beads wi...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.7b00206
更新日期：2017-07-24 00:00:00
abstract：:Structure-based virtual screening is highly used in the early stages of drug discovery to identify new putative lead compounds for a given target. However, when a small molecule elicits a biological effect, but its target is unknown, or the side effects it causes arise from its undesired interaction with unknown count...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.9b00428
更新日期：2019-11-25 00:00:00
abstract：:The worldwide increase and proliferation of drug resistant microbes, coupled with the lag in new drug development, represents a major threat to human health. In order to reduce the time and cost for exploring the chemical search space, drug discovery increasingly relies on computational biology approaches. One key ste...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.0c00075
更新日期：2020-06-22 00:00:00
abstract：:An important issue in developing protein-ligand docking methods is how to incorporate receptor flexibility. Consideration of receptor flexibility using an ensemble of precompiled receptor conformations or by employing an effectively enlarged binding pocket has been reported to be useful. However, direct consideration ...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci300342z
更新日期：2012-12-21 00:00:00
abstract：:Finding a canonical ordering of the atoms in a molecule is a prerequisite for generating a unique representation of the molecule. The canonicalization of a molecule is usually accomplished by applying some sort of graph relaxation algorithm, the most common of which is the Morgan algorithm. There are known issues with...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.5b00543
更新日期：2015-10-26 00:00:00
abstract：:Increased reports of oseltamivir (OTV)-resistant strains of the influenza virus, such as the H274Y mutation on its neuraminidase (NA), have created some cause for concern. Many studies have been conducted in the attempt to uncover the mechanism of OTV resistance in H274Y NA. However, most of the reported studies on H2...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.5b00331
更新日期：2016-01-25 00:00:00
abstract：:Human telomeric DNA G-quadruplex has been identified as a good therapeutic target in cancer treatment. G-quadruplex-specific ligands that stabilize the G-quadruplex have great potential to be developed as anticancer agents. Two crystal structures (an apo form of parallel stranded human telomeric G-quadruplex and its h...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.7b00287
更新日期：2017-11-27 00:00:00
abstract：:With the emergence of large collections of protein-ligand complexes complemented by binding data, as found in PDBbind or BindingMOAD, new opportunities for parametrizing and evaluating scoring functions have arisen. With huge data collections available, it becomes feasible to fit scoring functions in a QSAR style, i.e...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci100264e
更新日期：2010-11-22 00:00:00
abstract：:In this study, in order to elucidate the action mechanism of traditional Chinese medicines (TCMs) that exhibit clinical efficacy for type II diabetes mellitus (T2DM), an integrated protocol that combines molecular docking and pharmacophore mapping was employed to find the potential inhibitors from TCM for the T2DM-rel...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci400146u
更新日期：2013-07-22 00:00:00
abstract：:Large ring cyclodextrins have become increasingly important for drug delivery applications. In this work, we have performed replica-exchange molecular dynamics simulations using both implicit and explicit water solvation models to study the conformational diversity of iota-cyclodextrin containing 14 α-1,4 glycosidic l...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.6b00595
更新日期：2017-04-24 00:00:00
abstract：:The cannabinoid receptor subtype 2 (CB2) is a promising therapeutic target for blood cancer, pain relief, osteoporosis, and immune system disease. The recent withdrawal of Rimonabant, which targets another closely related cannabinoid receptor (CB1), accentuates the importance of selectivity for the development of CB2 ...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci3003914
更新日期：2013-01-28 00:00:00
abstract：:DiSCuS, a "Database System for Compound Selection", has been developed. The primary goal of DiSCuS is to aid researchers in the steps subsequent to generating high-throughput virtual screening (HTVS) results, such as selection of compounds for further study, purchase, or synthesis. To do so, DiSCuS provides (1) a stor...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci400587f
更新日期：2014-01-27 00:00:00
abstract：:We present an induced fit docking approach called Adaptive BP-Dock that integrates perturbation response scanning (PRS) with the flexible docking protocol of RosettaLigand in an adaptive manner. We first perturb the binding pocket residues of a receptor and obtain a new conformation based on the residue response fluct...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.5b00587
更新日期：2016-04-25 00:00:00
abstract：:In the present study, we report the exploration of binding modes of potent HIV-1 integrase (IN) inhibitors MK-0518 (raltegravir) and GS-9137 (elvitegravir) as well as chalcone and related amide IN inhibitors we recently synthesized and the development of 3D-QSAR models for integrase inhibition. Homology models of DNA-...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci200485a
更新日期：2012-02-27 00:00:00
abstract：:An ultrafast docking and virtual screening program, CRDOCK, is presented that contains (1) a search engine that can use a variety of sampling methods and an initial energy evaluation function, (2) several energy minimization algorithms for fine tuning the binding poses, and (3) different scoring functions. This modula...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci300194a
更新日期：2012-08-27 00:00:00
abstract：:In structure-based drug design, scoring functions are often employed to evaluate protein-ligand interactions. A variety of scoring functions have been developed so far, and thus, some objective benchmarks are desired for assessing their strength and weakness. The comparative assessment of scoring functions (CASF) benc...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.8b00545
更新日期：2019-02-25 00:00:00
abstract：:The accurate prediction of the adsorption energies of unsaturated molecules on graphene in the presence of water is essential for the design of molecules that can modify its properties and that can aid its processability. We here show that a semiempirical MO method corrected for dispersive interactions (PM6-DH2) can p...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci5003729
更新日期：2014-08-25 00:00:00
abstract：:Factor Xa inhibitors are innovative anticoagulant agents that provide a better safety/efficacy profile compared to other anticoagulative drugs. A chemical feature-based modeling approach was applied to identify crucial pharmacophore patterns from 3D crystal structures of inhibitors bound to human factor Xa (Pdb entrie...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci049778k
更新日期：2005-01-01 00:00:00
abstract：:Throughout the drug discovery process, discovery teams are compelled to use statistics for making decisions using data from a variety of inputs. For instance, teams are asked to prioritize compounds for subsequent stages of the drug discovery process, given results from multiple screens. To assist in the prioritizatio...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci600556v
更新日期：2007-05-01 00:00:00
abstract：:The antiproliferative factor (APF) involved in interstitial cystitis is a glycosylated nonapeptide (TVPAAVVVA) containing a sialylated core 1 α-O-disaccharide linked to the N-terminal threonine. The chemical structure of APF was deduced using spectroscopic techniques and confirmed using total synthesis. The synthetic ...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci400147s
更新日期：2013-05-24 00:00:00
abstract：:Advances in the development of high-throughput screening and automated chemistry have rapidly accelerated the production of chemical and biological data, much of them freely accessible through literature aggregator services such as ChEMBL and PubChem. Here, we explore how to use this comprehensive mapping of chemical ...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.9b00526
更新日期：2019-11-25 00:00:00
