Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “docking”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 757 records · Page 42Linked to original sources
PubMed1994

Design of a non-docking intraoperative electron beam applicator system.

A development of a non-docking system is described which enables collimation of an electron beam for intraoperative radiation therapy. This system, adapted to a linear accelerator (SATURNE 43-CGR MeV), has been designed to minimize the mechanical, electrical and tumor visualization problems associated with a docking system. A number of dosimetric considerations and technical innovations have been used in the design of this system. Among them are the central axis of the beam alignment with the axis of the cone via a laser system and the clamping method of the intraoperative cone to the treatment couch by a rigid system. This collimation system can be adapted for different makes of linear accelerator. The dose distribution in this new design system shows a better homogeneity in the patient's target volume and small (thus accessable) leakage radiation dose to tissues outside the intraoperative cone. The design concept and dosimetric characteristics of this novel applicator system are presented in this paper.

Acrylic Resins↗
PubMed1994

Specificity and regulation of a synaptic vesicle docking complex.

Synaptic vesicles are proposed to dock at the presynaptic plasma membrane through the interaction of two integral membrane proteins of synaptic vesicles, VAMP and synaptotagmin, and two plasma membrane proteins, syntaxin and SNAP-25. We have characterized the binding properties of these proteins and observed SNAP-25 potentiation of VAMP 2 binding to syntaxins 1a and 4 but not syntaxins 2 or 3. n-sec1, a neuron-specific syntaxin-binding protein, bound syntaxin with nanomolar affinity, forming a complex that is distinct from the previously identified 7S and 20S syntaxin-containing complexes. This suggests that syntaxin exists in at least three states: bound to n-sec1, in a 7S particle, and in a 20S particle. Recombinant n-sec1 inhibited VAMP or SNAP-25 binding to syntaxin. We propose that the specific associations of VAMP, SNAP-25, and syntaxin mediate vesicle docking and that a syntaxin/n-sec1 complex precedes and/or regulates formation of these complexes.

Amino Acid Sequence↗
PubMed1994

A post-docking role for synaptobrevin in synaptic vesicle fusion.

We have used the squid giant synapse to determine the role of synaptobrevin, integral membrane proteins of small synaptic vesicles, in neurotransmitter release. The sequence of squid synaptobrevin, deduced by cDNA cloning, is 65%-68% identical to mammalian isoforms and includes the conserved cleavage site for tetanus and botulinum B toxins. Injection of either toxin into squid nerve terminals caused a slow, irreversible inhibition of release without affecting the Ca2+ signal which triggers release. Microinjection of a recombinant protein corresponding to the cytoplasmic domain of synaptobrevin produced a more rapid and reversible inhibition of release, whereas two smaller peptide fragments were without effect. Electron microscopy of tetanus-injected terminals revealed an increased number of both docked and undocked synaptic vesicles. These data indicate that synaptobrevin participates in neurotransmitter release at a step between vesicle docking and fusion.

Amino Acid Sequence↗
PubMed1994

Mechanisms of vesicle docking and fusion: insights from the nervous system.

Upon stimulation of nerve cells, synaptic vesicles fuse with the presynaptic plasma membrane to release neurotransmitter. The biochemical pathway responsible for synaptic-vesicle docking and fusion is now being elucidated. Many of the proteins implicated in this process have homologs elsewhere in the cell. The docking and fusion mechanism discussed in this review may account for the specificity of vesicular trafficking throughout both regulated and constitutive secretory pathways.

Animals↗
PubMed1995

Docking small-molecule ligands into active sites.

Docking involves the development of computer algorithms that evaluate the binding modes of putative ligands in receptor sites. The principal advances of the past year have been the development of new algorithmic approaches, several of which incorporate conformational flexibility, and the increased use of docking to identify leads in drug-discovery programmes.

Algorithms↗
PubMed1995

Ligand-protein docking and rational drug design.

Over the past year there have been some interesting and significant advances in computer-based ligand-protein docking techniques and related rational drug-design tools, including flexible ligand docking and better estimation of binding free energies and solvation energies. As a result, the successful use of computational tools to help generate interesting new guide (lead) compounds for targeted receptors is becoming more commonplace.

Algorithms↗
PubMed2005

Characterization of binding site of closed-state KCNQ1 potassium channel by homology modeling, molecular docking, and pharmacophore identification.

This investigation was performed to assess the importance of interaction in the binding of blockers to KCNQ1 potassium using molecular modeling. This work could be considered made up by three main steps: (1) the construction of closed-state structure of KCNQ1 through homology modeling; (2) the automated docking of three blockers: IKS-142, L-735821, and BMS-IKS, using DOCK program; (3) the generation and validation of pharmacophore for KCNQ1 ligands using Catalyst/HypoGen. The obtained results highlight the hydrophobic or aromatic residues involved in S6 transmembrane domain and the base of the pore helix of KCNQ1, confirming the mutagenesis data and pharmacophore model, and giving new suggestions for the rational design of novel KCNQ1 ligands.

Amino Acid Sequence↗
PubMed2003

3-D-QSAR study and molecular docking of methionyl-tRNA synthetase inhibitors.

The three-dimensional quantitative structure-activity relationships of 57 2-[(aminopropyl)amino]-4(1H)-quinolinone analogues as Staphylococcus aureus methionyl-tRNA synthetase (MetRS) inhibitors with excellent antibacterial profile were investigated and docking studies were performed. The CoMFA analysis provided a model with a q(2) value of 0.579 and an r(2) value of 0.970, in which the good correlation between the MetRS inhibitory activities (IC(50)) and the steric and electrostatic molecular fields around the analogues was examined. Two inhibitors (1 and 17) were docked into the binding pocket of Escherichia coli MetRS imported from the X-ray crystal structure of the MetRS-methionine complex, and the details of their interaction with the amino acids of the active site are discussed.

Binding Sites↗
PubMed2004

Elucidating inhibitory models of the inhibitors of epidermal growth factor receptor by docking and 3D-QSAR.

Epidermal growth factor receptor (EGFR) protein tyrosine kinases (PTKs) are attractive targets for anti-tumor drug design. Although thousands of their ligands have been studied as potential inhibitors against PTKs, there is no QSAR study that covers different kinds of inhibitors with observable structural diversity. However, by using this approach, we could mine far more useful information. Hence in order to better understand the binding model and the relationship between the physicochemical properties and the inhibitory activities of different kind of various inhibitors, molecular docking and 3D-QSAR, viz. CoMFA and CoMSIA, were combined to study 124 reported inhibitors with different scaffolds. Based on the docked binding conformations, highly reliable and predictive 3D-QSAR models were derived, which reveal how steric, electrostatic, and hydrophobic interactions contribute to inhibitors' bioactivities. This result also demonstrates that it is possible to include different kinds of inhibitors with observable structural diversity into one 3D-QSAR study. Therefore, this study not only casts light on binding mechanism between EGFR and its inhibitors, but also provides new hints for de novo design of new EGFR inhibitors with observable structural diversity.

Crystallography, X-Ray↗
PubMed2004

Flexible docking of pyridinone derivatives into the non-nucleoside inhibitor binding site of HIV-1 reverse transcriptase.

Potent non-nucleoside reverse transcriptase inhibitors (NNRTIs) of the pyridinone derivative type were docked into nine NNRTIs binding pockets of HIV-1 reverse transcriptase (RT) structures. The docking results indicate that pyridinone analogues adopt a butterfly conformation and share the same binding mode as the crystal inhibitors in the pocket geometries of nevirapine, 1051U91, 9-Cl-TIBO, Cl-alpha-APA, efavirenz, UC-781, and S-1153. The results are in agreement with the data concerning mutational and structure-activity relationships available for pyridinone analogues and aid in the understanding, at the molecular level, of the biological response of published hybrid pyridinone molecules. Strategies to design further pyridinone derivatives active against RT containing mutations are discussed.

Anti-HIV Agents↗
PubMed2005

Understanding the structure-activity and structure-selectivity correlation of cyclic guanine derivatives as phosphodiesterase-5 inhibitors by molecular docking, CoMFA and CoMSIA analyses.

Molecular docking and 3D-QSAR analyses were performed to understand how PDE5 and PDE6 interact with a series of (49) cyclic guanine derivatives. Using the conformations of the compounds revealed by molecular docking, CoMFA and CoMSIA analyses resulted in the first quantitative structure-activity relationship (QSAR) and first quantitative structure-selectivity relationship (QSSR) models (with high cross-validated correlation coefficient q(2) and conventional correlation coefficient r(2) values) for predicting the inhibitory activity against PDE5 and the selectivity against PDE6. The high q(2) and r(2) values, along with further testing, indicate that the obtained 3D-QSAR and 3D-QSSR models will be valuable in predicting both the inhibitory activity and selectivity of cyclic guanine derivatives for these protein targets. A set of 3D contour plots drawn based on the 3D-QSAR and 3D-QSSR models reveal some useful clues to improve both the activity and selectivity by modifying structures of the compounds. It has been demonstrated that both the steric and electrostatic factors should appropriately be taken into account in future rational design and development of more active and more selective PDE5 inhibitors for the therapeutic treatment of erectile dysfunction (ED).

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed2005

3D-QSAR and docking studies of aldehyde inhibitors of human cathepsin K.

In order to better understand the structural and chemical features of human cathepsin K (CatK), which is an important cysteine protease in the pathogenesis of osteoporosis, the 3D-QSAR (CoMFA) studies were conducted on recently explored aldehyde compounds with known CatK inhibitory activities. The genetic algorithm of GOLD2.2 has been employed to position 59 aldehyde compounds into the active sites of CatK to determine the probable binding conformation. Good correlations between the predicted binding free energies and the experimental inhibitory activities suggested that the identified binding conformations of these potential inhibitors are reliable. The docking results also provided a reliable conformational alignment scheme for 3D-QSAR model. Based on the docking conformations, highly predictive comparative molecular field analysis (CoMFA) was performed with q2 value of 0.723. The predictive ability was validated by some compounds that were not included in the training set. Furthermore, the CoMFA model was mapped back to the binding sites of CatK, to get a better understanding of vital interactions between the aldehyde compounds and the protease. The CoMFA field distributions are in good agreement with the structural characteristics of the binding groove of the CatK, which suggested that the n-Bu in R4 position is the favor group substitute at P1 and moderate groups in R2 group are required on P2 substitute. In addition, 3D-QSAR results also demonstrated that aldehyde is an important pharmacophore because of electrostatic effect. These results, together with the good correlations between the inhibitory activities and the binding free energies predicted by GOLD2.2, demonstrated the power of combining docking/QSAR approach to explore the probable binding conformations of compounds at the active sites of the protein target, and further provided useful information in understanding the structural and chemical features of CatK in designing and finding new potential inhibitors.

Aldehydes↗
PubMed2005

Docking dinucleotides to HIV-1 integrase carboxyl-terminal domain to find possible DNA binding sites.

HIV-1 integrase mediates a processed viral DNA into the host genome DNA. The binding modes between HIV-1 integrase and viral/host DNA have not been clarified until now. The C-terminal domain of integrase has been found to be a DNA-binding domain. In this work, we have explored the possible DNA binding sites of dimeric C-terminal domain by docking dinucleotides to HIV-1 integrase. The docking results suggest that two symmetrical DNA-binding sites are likely located on the outside surface of the dimeric C-terminal domain and not located in the groove. Those sites are in agreement with the experimental data.

Binding Sites↗
PubMed2005

Molecular docking of the highly hypolipidemic agent alpha-asarone with the catalytic portion of HMG-CoA reductase.

Docking experiments using a number of published crystal structures of HMG-CoA reductase with the potent hypocholesterolemic agent alpha-asarone are described. The results indicate that alpha-asarone binds in the enzyme's active site. The methoxy groups play a key role in the binding and probably also in its biological activity, as shown by extensive SAR studies reported for analogues of alpha-asarone. The docking results will be valuable for the structure-based design of novel hypolipidemic agents.

Allylbenzene Derivatives↗
PubMed2005

Homology modeling and docking study of cyclin-dependent kinase (CDK) 10.

In order to understand the mechanisms of ligand binding and the interaction between the ligand and the cyclin-dependent kinase 10 (CDK10), a three-dimensional (3D) model of the CDK10 is generated based on the crystal structure of the cyclin-dependent kinase 2 (CDK2) (PDB code 1AQ1) by using InsightII/Homology module. With the aid of the molecular mechanics and molecular dynamics methods, the last refined model is obtained and is further assessed by PROFILE-3D and PROSTAT, which show that the refined model is reliable. With this model, a flexible docking study is performed and the results indicate that the Lys39 and Asp94 form hydrogen bonds and have strong nonbonding interaction with adenosine 5'-triphosphate (ATP). From the docking studies, we also suggest that the Leu141, Tyr21, and Val24 in CDK10 are three important determinant residues in binding as they have strong nonbonding interaction with ATP. The hydrogen bonding interactions also play an important role for the stability of the complex. Our results may be helpful for further experimental investigations.

Amino Acid Sequence↗
PubMed2005

Three-dimensional structure of Plasmodium falciparum Ca2+ -ATPase(PfATP6) and docking of artemisinin derivatives to PfATP6.

Construction of the 3D structure of PfATP6 by homology modeling and docking simulation of artemisinin derivatives to this protein model are reported. Docking and consequent LUDI scores show good relation with in vitro antimalarial activities. The main binding source of artemisinins to the PfATP6 is hydrophobic interaction and biologically important peroxide bonds were exposed to outside of the binding pocket. This study suggests binding of artemisinin to PfATP6 precedes activation of peroxide bond by Fe(2+) species.

Amino Acid Sequence↗
PubMed2006

Three-dimensional quantitative structure-activity relationship (3 D-QSAR) and docking studies on (benzothiazole-2-yl) acetonitrile derivatives as c-Jun N-terminal kinase-3 (JNK3) inhibitors.

Three-dimensional quantitative structure-activity relationship (3D-QSAR) models were developed for 44 (benzothiazole-2-yl) acetonitrile derivatives, inhibiting c-Jun N-terminal kinase-3 (JNK3). It includes molecular field analysis (MFA) and receptor surface analysis (RSA). The QSAR model was developed using 34 compounds and its predictive ability was assessed using a test set of 10 compounds. The predictive 3D-QSAR models have conventional r2 values of 0.849 and 0.766 for MFA and RSA, respectively; while the cross-validated coefficient r(cv)2 values of 0.616 and 0.605 for MFA and RSA, respectively. The results of the QSAR model were further compared with a structure-based analysis using docking studies with crystal structure of JNK3. Ligands bind in the ATP pocket and the hydrogen bond with GLN155 was found to be crucial for selectivity among other kinases. The results of 3D-QSAR and docking studies validate each other and hence, the combination of both methodologies provides a powerful tool directed to the design of novel and selective JNK3 inhibitors.

Acetonitriles↗
PubMed2006

3D QSAR studies of AChE inhibitors based on molecular docking scores and CoMFA.

Three-dimensional quantitative structure-activity relationship (3D QSAR) studies were performed on acetylcholinesterase (AChE) inhibitors, based on molecular docking scores obtained by using FlexX and FlexiDock and comparative molecular field analysis (CoMFA). The docking scores were used as molecular descriptors along with the steric and electrostatic field values of CoMFA, for partial least square (PLS) analysis. The high leave one out (LOO) cross-validated correlation coefficient (q(2)=0.714) reveals that the model is a useful tool for the prediction of test set as well as newly designed structures against AChE activity. The superimposed CoMFA models on the receptor site of AChE are guiding the design of potential inhibitory structures directed against AChE activity.

Acetylcholinesterase↗