Abstract:
:CC chemokine receptor 5 (CCR5), a member of G protein-coupled receptors (GPCRs), plays a vital role in inflammatory responses to infection. Alterations in the expression of CCR5 have been correlated with disease progression in many types of cancers. The idea of using CCR5 as a target for therapeutic intervention has been demonstrated to prevent disease progression. To date, only a few compounds have been reported as CCR5 inhibitors. In this study, a series of CCR5 antagonists were used to construct pharmacophore models. Then the optimal model was utilized as a 3D query to identify novel chemical entities from structural databases. After refinement by molecular docking, drug-likeness analysis, molecular dynamics simulations (MDS) and binding free energy analysis, three potential inhibitors (25, 29 and 45) were identified. MD simulations suggested that the screened compounds retained the important common binding mode known for CCR5 inhibitors (maraviroc and nifeviroc), which occupied the bottom of a pocket and stabilized the conformation of CCR5. During the binding process, van der Waals interactions provided the substantial driving force. The most favorable contributions were from Tyr37, Trp86, Tyr89, Tyr108, Phe109, Phe112, Gln194, Thr195, Ile198, Trp248, Tyr251, Leu255, Thr259, Met279, Glu283 and Met287. The above results suggest that the hybrid strategy would provide a basis for rational drug design.
journal_name
Mol Biosystjournal_title
Molecular bioSystemsauthors
Wang J,Shu M,Wang Y,Hu Y,Wang Y,Luo Y,Lin Zdoi
10.1039/c6mb00577bsubject
Has Abstractpub_date
2016-10-18 00:00:00pages
3396-3406issue
11eissn
1742-206Xissn
1742-2051journal_volume
12pub_type
杂志文章abstract::Recently circular RNA (circularRNA) has been discovered as an increasingly important type of long non-coding RNA (lncRNA), playing an important role in gene regulation, such as functioning as miRNA sponges. So it is very promising to identify circularRNA transcripts from de novo assembled transcripts obtained by high-...
journal_title:Molecular bioSystems
pub_type: 杂志文章
doi:10.1039/c5mb00214a
更新日期:2015-08-01 00:00:00
abstract::Herein, we demonstrate that the bacterial signaling molecule, c-di-GMP, can enhance the peroxidation of hemin when proflavine is present. The c-di-GMP-proflavine-hemin nucleotidezyme can oxidize the colorless compound 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid), ABTS, to the colored radical cation ABTS˙(+) ...
journal_title:Molecular bioSystems
pub_type: 杂志文章
doi:10.1039/c2mb05430b
更新日期:2012-03-01 00:00:00
abstract::A metabolomic study was performed to investigate the biochemical profiles of livers from male and female zebrafish (Danio rerio), using a multiple platform approach, incorporating 1H NMR, GC/MS and LC/MS. The reproducibility and reliability of the three methods were validated prior to the assays. Major biomolecules de...
journal_title:Molecular bioSystems
pub_type: 杂志文章
doi:10.1039/b811850g
更新日期:2009-03-01 00:00:00
abstract::Calcium (Ca(2+)) is used as a signaling molecule to regulate many cellular processes. Calcium signaling generally involves transient elevations of the concentration of free Ca(2+) in the cytosol. More pronounced and sustained elevations of intracellular Ca(2+) concentrations are observed during apoptosis (programmed c...
journal_title:Molecular bioSystems
pub_type: 杂志文章,评审
doi:10.1039/b920805d
更新日期:2010-05-01 00:00:00
abstract::The advent of large scale sequencing methods has enabled analyses of the protein-coding parts of cancer genomes to find the mutated genes that cause common human cancers. Unbiased mutation analyses of human tumors originating in the breast, colon, brain, and pancreas have revealed genomic landscapes composed of a few ...
journal_title:Molecular bioSystems
pub_type: 杂志文章,评审
doi:10.1039/b903502h
更新日期:2009-09-01 00:00:00
abstract::Integrative pharmacology has been used to identify the key active constituents (KACs) of Buchang Naoxintong capsules (BNCs), a traditional Chinese medical preparation; this approach involves the evaluation of the content profiles and drug-like properties of the BNC constituents and development of an ingredient-target ...
journal_title:Molecular bioSystems
pub_type: 杂志文章
doi:10.1039/c5mb00460h
更新日期:2016-01-01 00:00:00
abstract::Cellular heterogeneity and stochastic fluctuation play key roles in biological processes. Single molecule approaches have the key advantage of avoiding ensemble averaging, allowing the observation of transient intermediates and heterogeneity (both static and dynamic). Thus they have revolutionised the way many biologi...
journal_title:Molecular bioSystems
pub_type: 杂志文章
doi:10.1039/b702845h
更新日期:2007-06-01 00:00:00
abstract::Disordered regions within proteins have increasingly been associated with various cellular functions. Identifying the specific roles played by disorder in these functions has proved difficult. However, the development of reliable prediction algorithms has expanded the study of disorder from a few anecdotal examples to...
journal_title:Molecular bioSystems
pub_type: 杂志文章,评审
doi:10.1039/c1mb05235g
更新日期:2012-01-01 00:00:00
abstract::Cervical cancer is a clinical and pathological heterogeneity disease, which requires different types of treatments and leads to a variety of outcomes. In clinical practice, only some patients benefit from chemotherapy treatment. Identifying patients who will be responsive to chemotherapy could increase their survival ...
journal_title:Molecular bioSystems
pub_type: 杂志文章
doi:10.1039/c4mb00054d
更新日期:2014-08-01 00:00:00
abstract::J proteins are a diverse family of co-chaperones that cooperate with heat shock protein 70 (Hsp70) to coordinate protein quality control, especially in response to cellular stress. Current models suggest that individual J proteins might play roles in recruiting Hsp70s to specific functions, such as maintaining cell wa...
journal_title:Molecular bioSystems
pub_type: 杂志文章
doi:10.1039/c2mb25248a
更新日期:2012-11-01 00:00:00
abstract::Establishing functional relationships between multi-domain protein sequences is a non-trivial task. Traditionally, delineating functional assignment and relationships of proteins requires domain assignments as a prerequisite. This process is sensitive to alignment quality and domain definitions. In multi-domain protei...
journal_title:Molecular bioSystems
pub_type: 杂志文章
doi:10.1039/c3mb70443b
更新日期:2014-05-01 00:00:00
abstract::Insights into the structure and dynamics of modular polyketide synthases (PKS) are essential for understanding the mechanistic details of the biosynthesis of a large number of pharmaceutically important secondary metabolites. The crystal structures of the KS-AT di-domain from erythromycin synthase have revealed the re...
journal_title:Molecular bioSystems
pub_type: 杂志文章
doi:10.1039/c2mb05425f
更新日期:2012-04-01 00:00:00
abstract::Here, we used stopped-flow fluorescence techniques to conduct a comparative kinetic analysis of the conformational transitions in human apurinic/apyrimidinic endonuclease 1 (APE1) and in DNA containing an abasic site in the course of their interaction. Effects of monovalent (K(+)) and divalent (Mg(2+), Mn(2+), Ca(2+),...
journal_title:Molecular bioSystems
pub_type: 杂志文章
doi:10.1039/c6mb00128a
更新日期:2016-05-26 00:00:00
abstract::Mimicking receptor flexibility during receptor-ligand binding is a challenging task in computational drug design since it is associated with a large increase in the conformational search space. In the present study, we have devised an in silico design strategy incorporating receptor flexibility in virtual screening to...
journal_title:Molecular bioSystems
pub_type: 杂志文章
doi:10.1039/c4mb00307a
更新日期:2014-10-01 00:00:00
abstract::It is well known that oligomeric/aggregated amyloid β peptides are a key player in the pathogenesis of Alzheimer's disease and that different nanoparticles influence oligomerization/aggregation processes in experiments in vitro. Our previous results demonstrated antiaggregation effects of magnetite nanoparticles in th...
journal_title:Molecular bioSystems
pub_type: 杂志文章
doi:10.1039/c003498c
更新日期:2010-11-01 00:00:00
abstract::Ligand-induced conditional protein splicing (CPS) using a split intein allows the covalent reconstitution of a protein from two polypeptide fragments. The small molecule rapamycin binds to the fused FKBP and FRB dimerizer domains and thereby induces folding of the split intein, which then removes itself in the trans-s...
journal_title:Molecular bioSystems
pub_type: 杂志文章
doi:10.1039/c1mb05025g
更新日期:2011-06-01 00:00:00
abstract::Protein-protein interactions are important for the majority of biological processes. A significant number of computational methods have been developed to predict protein-protein interactions using protein sequence, structural and genomic data. Vast experimental data is publicly available on the Internet, but it is sca...
journal_title:Molecular bioSystems
pub_type: 杂志文章
doi:10.1039/c3mb70486f
更新日期:2014-04-01 00:00:00
abstract::Induced reprogramming of somatic cells has had a great impact on stem cell research, and the reprogramming technologies have evolved from four transgenic factors (Oct4, Sox2, Klf4, and c-Myc; OSKM) to just a few microRNAs (mainly miR-290/302 seed family). Despite these advances, the molecular events occurring during v...
journal_title:Molecular bioSystems
pub_type: 杂志文章,评审
doi:10.1039/c2mb25088h
更新日期:2013-01-27 00:00:00
abstract::The biosynthesis of the endocannabinoid anandamide (AEA) and related N-acyl ethanolamine (NAE) lipids is complex and appears to involve multiple pathways, including: (1) direct release of NAEs from N-acyl phosphatidyl ethanolamine (NAPE) precursors by the phosphodiesterase NAPE-PLD, and (2) double O-deacylation of NAP...
journal_title:Molecular bioSystems
pub_type: 杂志文章
doi:10.1039/c000237b
更新日期:2010-08-01 00:00:00
abstract::The neuroscientific community rapidly adopted RNA interference techniques as an experimental tool for the dissection of gene function in vitro and in animal models of neurological disease in vivo. Here, we discuss recent advances in the biotechnical implementation of siRNA/shRNA-mediated gene silencing focusing on iss...
journal_title:Molecular bioSystems
pub_type: 杂志文章,评审
doi:10.1039/b701169e
更新日期:2007-11-01 00:00:00
abstract::The mono-site mutations of the absolutely conserved residues, (464)LGR(466), in the α-helix 5 (h5) of HPV16 L1 completely disrupted the pentamer formation. The implication of this finding is the potential usage of a h5-like peptide as the reagent to interfere with the pentamer formation and stability as an anti-HPV re...
journal_title:Molecular bioSystems
pub_type: 杂志文章
doi:10.1039/c3mb70550a
更新日期:2014-04-01 00:00:00
abstract::The underlying reasons for the differences in the virulence of various types of Ebola virus (EBOV) remain unknown. Comparison of the percentage of disorder (PID) in nucleocapsid proteins VP30 and NP reveals high correlation between nucleocapsid PIDs and the case-fatality rates of EBOV. The higher disorder of these pro...
journal_title:Molecular bioSystems
pub_type: 杂志文章
doi:10.1039/c5mb00240k
更新日期:2015-08-01 00:00:00
abstract::Naphthalene, a polycyclic aromatic hydrocarbon, is a ubiquitous environmental pollutant capable of causing illness. In this study, we deconvoluted the metabolites related to naphthalene intervention in various organs by using nuclear magnetic resonance (NMR) and liquid chromatography-tandem mass spectrometry (LC-MS/MS...
journal_title:Molecular bioSystems
pub_type: 杂志文章
doi:10.1039/c4mb00090k
更新日期:2014-07-01 00:00:00
abstract::Calcium homeostasis is a key factor in the regulation of cardiac excitation-contraction coupling. Calcium dynamics in cardiomyocytes is governed by ATP which depends on insulin dependent glucose concentration, via the glucose transporter type 4 (GLUT4) transporter. It would therefore be interesting to see how calcium ...
journal_title:Molecular bioSystems
pub_type: 杂志文章
doi:10.1039/c7mb00264e
更新日期:2017-09-26 00:00:00
abstract::The protein kinase C (PKC) family of serine/threonine kinases is an attractive drug target for the treatment of cancer and other diseases. Diacylglycerol (DAG), phorbol esters and others act as ligands for the C1 domain of PKC isoforms. Inspection of the crystal structure of the PKCδ C1b subdomain in complex with phor...
journal_title:Molecular bioSystems
pub_type: 杂志文章
doi:10.1039/c2mb05452c
更新日期:2012-04-01 00:00:00
abstract::The size and complexity of cellular systems make building predictive models an extremely difficult task. In principle dynamical time-course data can be used to elucidate the structure of the underlying molecular mechanisms, but a central and recurring problem is that many and very different models can be fitted to exp...
journal_title:Molecular bioSystems
pub_type: 杂志文章
doi:10.1039/c0mb00107d
更新日期:2011-05-01 00:00:00
abstract::Production of biofuels has been one of the promising efforts in biotechnology in the past few decades. The perspective of these efforts can be reduction of increasing demands for fossil fuels and consequently reducing environmental pollution. Nonetheless, most previous approaches did not succeed in obviating many big ...
journal_title:Molecular bioSystems
pub_type: 杂志文章
doi:10.1039/c6mb00119j
更新日期:2016-07-19 00:00:00
abstract::The emergence of drug resistant strains of Mycobacterium Tuberculosis (Mtb) accentuates the urgent need for the development of novel antitubercular drugs. The major causes of drug resistance are genetic mutations, the influx-efflux transporter system, and the complex cell wall system of Mtb, which can function as perm...
journal_title:Molecular bioSystems
pub_type: 杂志文章
doi:10.1039/c6mb00457a
更新日期:2016-10-18 00:00:00
abstract::4-Aminoantipyrine (AAP) is scarcely administered as an analgesic drug because of the potential side effects. The residue of AAP in the environment possesses a potential threat to human health. In this article, the binding mode of AAP with the important antioxidant enzyme catalase (CAT) was investigated using spectrosc...
journal_title:Molecular bioSystems
pub_type: 杂志文章
doi:10.1039/c1mb05271c
更新日期:2011-11-01 00:00:00
abstract::In this review we bring together recent results from our group focused towards the development of biosensors from single conically-shaped artificial nanopores. The nanopores, used in the work presented here, were prepared using the track-etch process. The fabrication of track-etched conical nanopores has been optimize...
journal_title:Molecular bioSystems
pub_type: 杂志文章,评审
doi:10.1039/b708725j
更新日期:2007-10-01 00:00:00