Abstract：
:The pharmacophoric concept plays an important role in ligand-based drug design methods to describe the similarity and diversity of molecules, and could also be exploited as a molecular representation scheme. A three-point pharmacophore method was used as a molecular representation perception. This procedure was implemented for dopamine antagonists of the D(2) receptor subtype. The molecular structures of the antagonists included in this analysis were categorized into two structurally distinct classes. Using structural superposition with internal energy minimization, two pharmacophore models were deduced. Based on these two models other D(2) antagonists that fulfil them were derived and studied. This procedure aided the identification of the common 3D patterns present in diverse molecules that act at the same biological target and the extraction of a common molecular framework for the two structural classes. The pharmacophoric information was found to be suitable for guiding superposition of structurally diverse molecules, using a more biologically meaningful selection of the targeting points.
journal_name
J Comput Aided Mol Desjournal_title
Journal of computer-aided molecular designauthors
Atlamazoglou V,Thireou T,Eliopoulos Edoi
10.1007/s10822-007-9110-6subject
Has Abstractpub_date
2007-05-01 00:00:00pages
239-49issue
5eissn
0920-654Xissn
1573-4951journal_volume
21pub_type
杂志文章abstract：:We used blind predictions of the 47 hydration free energies in the SAMPL4 challenge to test multiple partial charge models in the context of explicit solvent free energy simulations with the general AMBER force field. One of the partial charge models, IPolQ-Mod, is a fast continuum solvent-based implementation of the ...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-014-9714-6
更新日期：2014-03-01 00:00:00
abstract：:The establishment of quantitative structure-activity relationship (QSAR) models for the toxicity of polycylic aromatic hydrocarbons (PAHs) is described. Two properties, in vitro percutaneous absorption in rat skin and discrete levels of carcinogenic activity, are examined using molecular quantum similarity measures (M...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1023/a:1011150003086
更新日期：2001-01-01 00:00:00
abstract：:Moment descriptors of the molecular charge and mass distributions are investigated within the context of molecular similarity. Euclidean distances in the moment descriptor space are shown to yield molecular proximities in accord with chemical intuition for a substituted [(4-phenylpiperazinyl)-methyl] benzamide series ...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1023/a:1008064003409
更新日期：1998-11-01 00:00:00
abstract：:G Protein-Coupled Receptors (GPCRs) constitute a superfamily of receptors that forms an important therapeutic target. The number of known GPCR sequences and related information increases rapidly. For these reasons, we are developing the Viseur program to integrate the available information related to GPCRs. The Viseur...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1023/a:1008170432484
更新日期：1999-11-01 00:00:00
abstract：:A series of non-peptide angiotensin II receptor antagonists was investigated with the aim of developing a 3D QSAR model using comparative molecular field analysis descriptors and approaches. The main goals of the study were dictated by an interest in methodologies and an understanding of the binding requirements to th...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/BF00134180
更新日期：1996-12-01 00:00:00
abstract：:Toxoplasma (T.) gondii, the causative agent of toxoplasmosis, is a ubiquitous opportunistic pathogen that infects individuals worldwide, and is a leading cause of severe congenital neurologic and ocular disease in humans. No vaccine to protect humans is available, and hypersensitivity and toxicity limit the use of the...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-011-9420-6
更新日期：2011-05-01 00:00:00
abstract：:To rigorously assess the tools and protocols that can be used to understand and predict macromolecular recognition, and to gain more structural insight into three newly discovered allosteric binding sites on a critical drug target involved in the treatment of HIV infections, the Olson and Levy labs collaborated on the...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-014-9709-3
更新日期：2014-04-01 00:00:00
abstract：:In the 1960s, the kappa statistic was introduced for the estimation of chance agreement in inter- and intra-rater reliability studies. The kappa statistic was strongly pushed by the medical field where it could be successfully applied via analyzing diagnoses of identical patient groups. Kappa is well suited for classi...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-014-9759-6
更新日期：2014-11-01 00:00:00
abstract：:Although auxins were the first type of plant hormone to be identified, little is known about the molecular mechanism of this important class of plant hormones. We present a classification of a set of about 50 compounds with measured auxin activities, according to their interaction properties. Four classes of compounds...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1023/a:1007973008558
更新日期：1998-01-01 00:00:00
abstract：:Many commercially available software programs claim similar efficiency and accuracy as variable selection tools. Genetic algorithms are commonly used variable selection methods where most relevant variables can be differentiated from 'less important' variables using evolutionary computing techniques. However, differen...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-004-5322-1
更新日期：2004-07-01 00:00:00
abstract：:Molecular modeling methodologies such as molecular docking, pharmacophore modeling, and 3D-QSAR, rely on conformational searches of small molecules as a starting point. All of these methodologies seek conformations of the small molecules as they bind to target proteins, i.e., their active conformations. Thus the quest...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1023/a:1016320106741
更新日期：2002-02-01 00:00:00
abstract：:The mounting evidences have shown that signal transducer and activator of transcription 3 (Stat3) is a critical target for cancer therapy. Recently, we developed a G-quartet oligonucleotide T40214 as a novel and potent Stat3 inhibitor. T40214 specifically inhibited DNA-binding activity of Stat3 and significantly suppr...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-007-9147-6
更新日期：2007-10-01 00:00:00
abstract：:Orientation of ten water molecules bound strongly at the contact surface of the dihydrofolate reductase-methotrexate enzyme-inhibitor complex was determined theoretically. To optimize the orientation of the water molecules, a recent method based on a simple electrostatic model was applied. The electrostatic complement...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/BF01532054
更新日期：1988-04-01 00:00:00
abstract：:R67 dihydrofolate reductase (DHFR), a bacterial plasmid-encoded enzyme associated with resistance to the drug trimethoprim, shows neither sequence nor structural homology with the chromosomal DHFR. It presents a highly symmetrical toroidal structure, where four identical monomers contribute to the unique central activ...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-005-3693-6
更新日期：2005-03-01 00:00:00
abstract：:Leishmania donovani dipeptidylcarboxypeptidsae (LdDCP), an angiotensin converting enzyme (ACE) related metallopeptidase has been identified and characterized as a putative drug target for antileishmanial chemotherapy. The kinetic parameters for LdDCP with substrate, Hip-His-Leu were determined as, Km, 4 mM and Vmax, 1...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-009-9315-y
更新日期：2010-01-01 00:00:00
abstract：:The Ligand Design (LUDI) approach has been used in order to design leucine aminopeptidase inhibitors, predict their activity and analyze their interactions with the enzyme. The investigation was based on the crystal structure of bovine lens leucine aminopeptidase (LAP) complexed with its inhibitor--the phosphonic acid...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1023/a:1008189716955
更新日期：2000-08-01 00:00:00
abstract：:The electron-conformational (EC) method in QSAR problems employs a unique (based on first principles) descriptor of molecular properties that incorporates the electronic structure and topology of the molecule and is presented in a digital-matrix form suitable for computer processing, the EC matrix of congruity (ECMC)....
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-008-9191-x
更新日期：2008-06-01 00:00:00
abstract：:A dataset of 82 protein-ligand complexes of known 3D structure and binding constant Ki was analysed to elucidate the important factors that determine the strength of protein-ligand interactions. The following parameters were investigated: the number and geometry of hydrogen bonds and ionic interactions between the pro...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章,评审
doi：10.1023/a:1007999920146
更新日期：1998-07-01 00:00:00
abstract：:Aromatic amino acid residues are often present in carbohydrate-binding sites of proteins. These binding sites are characterized by a placement of a carbohydrate moiety in a stacking orientation to an aromatic ring. This arrangement is an example of CH/pi interactions. Ab initio interaction energies for 20 carbohydrate...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-005-9033-z
更新日期：2005-12-01 00:00:00
abstract：:This paper describes a new and efficient stochastic conformational sampling method for generating a range of low-energy molecule conformations. Sampling can be tailored to a specific structural domain (e.g., peptides) by extracting torsional profiles from specific datasets and subsequently applying them to target mole...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-007-9156-5
更新日期：2008-09-01 00:00:00
abstract：:Even though it is highly toxic, Amphotericin B (AmB), an amphipathic polyene macrolide antibiotic, is used in the treatment of severe systemic fungal infections as a life-saving drug. To examine the influence of conformational factors on selective toxicity of these compounds, we have investigated the conformational pr...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1023/a:1008144208706
更新日期：2000-10-01 00:00:00
abstract：:Recent progress in molecular biology has revealed that many non-coding RNAs regulate gene expression or catalyze biochemical reactions in tumors, viruses and several other diseases. The tertiary structure of RNA molecules and RNA-RNA/protein interaction sites are of increasing importance as potential targets for new m...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-019-00195-y
更新日期：2019-05-01 00:00:00
abstract：:Evidenced by the three-rounds of G-protein coupled receptors (GPCR) Dock competitions, improving homology modeling methods of helical transmembrane proteins including the GPCRs, based on templates of low sequence identity, remains an eminent challenge. Current approaches addressing this challenge adopt the philosophy ...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-014-9823-2
更新日期：2015-05-01 00:00:00
abstract：:The growing number of protein-ligand complex structures, particularly the structures of proteins co-bound with different ligands, in the Protein Data Bank helps us tackle two major challenges in molecular docking studies: the protein flexibility and the scoring function. Here, we introduced a systematic strategy by us...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-017-0038-1
更新日期：2017-08-01 00:00:00
abstract：:The overexpression and/or mutation of the epidermal growth factor receptor (EGFR) tyrosine kinase has been observed in many human solid tumors, and is under intense investigation as a novel anticancer molecular target. Comparative 3D-QSAR analyses using different alignments were undertaken employing comparative molecu...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1023/b:jcam.0000004622.13865.4f
更新日期：2003-08-01 00:00:00
abstract：:A three-dimensional quantitative spectrometric data-activity relationship (3D-QSDAR) modeling technique which uses NMR spectral and structural information that is combined in a 3D-connectivity matrix has been developed. A 3D-connectivity matrix was built by displaying all possible assigned carbon NMR chemical shifts, ...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1023/a:1022479510524
更新日期：2002-10-01 00:00:00
abstract：:The use of MP2 level quantum mechanical (QM) calculations on isolated heteroaromatic ring systems for the prediction of the tautomeric propensities of whole molecules in a crystalline environment was examined. A Polarisable Continuum Model was used in the calculations to account for environment effects on the tautomer...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-010-9345-5
更新日期：2010-06-01 00:00:00
abstract：:Pharmacophore methods provide a way of establishing a structure activity relationship for a series of known active ligands. Often, there are several plausible hypotheses that could explain the same set of ligands and, in such cases, it is important that the chemist is presented with alternatives that can be tested wit...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-004-5523-7
更新日期：2004-11-01 00:00:00
abstract：:The free fatty acid receptor 1 (FFAR1, formerly GPR40), is a potential G protein-coupled receptor (GPCR) target for the treatment of type 2 diabetes mellitus (T2DM), as it enhances glucose-dependent insulin secretion upon activation by endogenous long-chain free fatty acids. The presence of two allosterically communic...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-020-00338-6
更新日期：2020-11-01 00:00:00
abstract：:Utilization of coupling constants as restraints in computational structure refinement is reviewed. In addition, we address the effect of conformational averaging and examine different approaches to apply the restraints when the experimental observable is obviously a result of averaging. Here, two different computation...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/BF00124347
更新日期：1994-02-01 00:00:00
