Abstract：
:Molecular modeling techniques and three-dimensional (3D) pattern analysis have been used to investigate the chemical and steric properties of compounds that inhibit transport of the plant hormone auxin. These compounds bind to a specific site on the plant plasma membrane characterized by its affinity for the herbicide N-1-naphthylphthalamic acid (NPA). A 3D model was derived from critical features of a set of ligands for the NPA receptor, a suggested binding conformation is proposed, and implications for the topographical features of the NPA receptor are discussed. This model, along with 3D structural analysis techniques, was then used to search the Abbott corporate database of chemical structures. Of the 467 compounds that satisfied the criteria of the model, 77 representative molecules were evaluated for their ability to compete for the binding of [3H]NPA to corn microsomal membranes. Nineteen showed activity that ranged from 16 to 85% of the maximum NPA binding. Four of the most active of these, representing chemical classes not included in the original compound set, were also found to inhibit polar auxin transport through corn coleoptile sections. Thus, this study demonstrates that 3D analysis techniques can identify active, novel ligands for biochemical target sites with concomitant physiological activity.
journal_name
J Comput Aided Mol Desjournal_title
Journal of computer-aided molecular designauthors
Bures MG,Black-Schaefer C,Gardner Gdoi
10.1007/BF00126666subject
Has Abstractpub_date
1991-08-01 00:00:00pages
323-34issue
4eissn
0920-654Xissn
1573-4951journal_volume
5pub_type
杂志文章abstract：:We apply an atomistic model of passive membrane permeability to a series of weakly basic drugs. The computational model uses conformational sampling in combination with an all-atom force field and implicit solvent model to estimate relative passive membrane permeabilities. The model does not require the use of trainin...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-007-9141-z
更新日期：2007-12-01 00:00:00
abstract：:Bradykinin (BK) is a member of the kinin family, released in response to inflammation, trauma, burns, shock, allergy and some cardiovascular diseases, provoking vasodilatation and increased vascular permeability among other effects. Their actions are mediated through at least two G-protein coupled receptors, B1 a rece...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-015-9890-z
更新日期：2016-01-01 00:00:00
abstract：:ERG-associated protein with the SET domain (ESET/SET domain bifurcated 1/SETDB1/KMT1E) is a histone lysine methyltransferase (HKMT) and it preferentially tri-methylates lysine 9 of histone H3 (H3K9me3). SETDB1/ESET leads to heterochromatin condensation and epigenetic gene silencing. These functional changes are report...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-017-0052-3
更新日期：2017-10-01 00:00:00
abstract：:Computational prediction of the effects of residue changes on peptide-protein binding affinities, followed by experimental testing of the top predicted binders, is an efficient strategy for the rational structure-based design of peptide inhibitors. In this study we apply this approach to the discovery of competitive a...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-012-9574-x
更新日期：2012-07-01 00:00:00
abstract：:The design of molecules with desired properties is still a challenge because of the largely unpredictable end results. Computational methods can be used to assist and speed up this process. In particular, genetic algorithms have proved to be powerful tools with a wide range of applications, e.g. in the field of drug d...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1023/a:1021928016359
更新日期：2002-08-01 00:00:00
abstract：:We describe a software tool that allows one to visualize and analyze the importance of each individual steric interaction in a molecular mechanics force field. ANLIZE is presently implemented for the Dreiding force field for use with the Cerius2 software package, but could be implemented in any molecular mechanics pac...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1023/a:1008070106973
更新日期：1997-03-01 00:00:00
abstract：:Intercalative binding of the antitumor drugs amonafide and azonafide to the oligonucleotide duplex d(GGCCGGCCGG).d(CCGGCCGGCC) was compared using molecular dynamics in vacuum with the AMBER force field. A number of reasonable possible binding conformations were obtained, with the azonafide complexes favored over the a...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/BF00402824
更新日期：1996-04-01 00:00:00
abstract：:In the present study, the binding free energy of a family of huprines with acetylcholinesterase (AChE) is calculated by means of the free energy perturbation method, based on hybrid quantum mechanics and molecular mechanics potentials. Binding free energy calculations and the analysis of the geometrical parameters hig...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-018-0114-1
更新日期：2018-05-01 00:00:00
abstract：:We have used the Chemical Structure DataBase (CSDB) of the NCI CADD Group, an aggregated collection of over 150 small-molecule databases totaling 103.5 million structure records, to conduct tautomerism analyses on one of the largest currently existing sets of real (i.e. not computer-generated) compounds. This analysis...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-010-9346-4
更新日期：2010-06-01 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
abstract：:All-atom molecular dynamics computer simulations were used to blindly predict the hydration free energies of a range of chloro-organic compounds as part of the SAMPL3 challenge. All compounds were parameterized within the framework of the OPLS-AA force field, using an established protocol to compute the absolute hydra...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-011-9527-9
更新日期：2012-05-01 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：:Atomic-resolution structures of the transmembrane 7-alpha-helical domains of 26 G-protein-coupled receptors (GPCRs) (including opsins, cationic amine, melatonin, purine, chemokine, opioid, and glycoprotein hormone receptors and two related proteins, retinochrome and Duffy erythrocyte antigen) were calculated by distan...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章,评审
doi：10.1023/a:1008050821744
更新日期：1999-07-01 00:00:00
abstract：:Quantitative structure-property relationship (QSPR) modeling of stability constants for the metal:ligand ratio 1:1 (logK) and 1:2 (logβ2) complexes of 3 transition metal ions with diverse organic ligands in aqueous solution was performed using ensemble multiple linear regression analysis and substructural molecular fr...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-014-9741-3
更新日期：2014-05-01 00:00:00
abstract：:The complex of adenylate kinase with its transition-state inhibitor has been studied by molecular dynamics simulations in water and in vacuum environments with the GROMOS force field over a period of 300 ps. The adenylate kinase, a member of the nucleotide-binding protein family, was exemplarily chosen for the inspect...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/BF00125373
更新日期：1994-08-01 00:00:00
abstract：:This paper describes several case studies concerning protein function inference from its structure using our novel approach described in the accompanying paper. This approach employs family-specific motifs, i.e. three-dimensional amino acid packing patterns that are statistically prevalent within a protein family. For...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-009-9277-0
更新日期：2009-11-01 00:00:00
abstract：:The Fas antigen, a cell surface receptor belonging to the tumor necrosis factor receptor (TNFR) superfamily, triggers programmed cell death (apoptosis) in the immune system. The three-dimensional structure of Fas and molecular details of the interaction between Fas and its ligand are currently unknown. A three-dimensi...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1023/a:1008011024584
更新日期：1997-01-01 00:00:00
abstract：:The conformational preferences of 12 molecular substructures in the crystalline state have been determined and compared with those predicted for relevant model compounds by ab initio molecular orbital calculations. Least-squares regression shows that there is a statistically significant correlation between the crystal...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/BF00355046
更新日期：1996-06-01 00:00:00
abstract：:A MD simulation protocol was developed to model halogen bonding in protein-ligand complexes by inclusion of a charged extra point to represent the anisotropic distribution of charge on the halogen atom. This protocol was then used to simulate the interactions of cathepsin L with a series of halogenated and non-halogen...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-014-9802-7
更新日期：2015-01-01 00:00:00
abstract：:New methods for docking, template fitting and building pseudo-receptors are described. Full conformational searches are carried out for flexible cyclic and acyclic molecules. QXP (quick explore) search algorithms are derived from the method of Monte Carlo perturbation with energy minimization in Cartesian space. An ad...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1023/a:1007907728892
更新日期：1997-07-01 00:00:00
abstract：:A structure-binding activity relationship for the intestinal bile acid transporter has been developed using data from a series of bile acid analogs in a comparative molecular field analysis (CoMFA). The studied compounds consisted of a series of bile acid-peptide conjugates, with modifications at the 24 position of th...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1023/a:1007919704457
更新日期：1997-11-01 00:00:00
abstract：:The V2 vasopressin renal receptor (V2R), which controls antidiuresis in mammals, is a member of the large family of heptahelical transmembrane (7TM) G protein-coupled receptors (GPCRs). Using the automated GPCR modeling facility available via Internet (http:/(/)expasy.hcuge.ch/swissmod/SWISS-MODEL.+ ++html) for constr...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1023/a:1007969526447
更新日期：1998-05-01 00:00:00
abstract：:Data driven decision making is a key element of today's pharmaceutical research, including early drug discovery. It comprises questions like which target to pursue, which chemical series to pursue, which compound to make next, or which compound to select for advanced profiling and promotion to pre-clinical development...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-015-9871-2
更新日期：2015-09-01 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：:This paper tests the performance of a simple empirical scoring function on a set of candidate designs produced by a de novo design package. The scoring function calculates approximate ligand-receptor binding affinities given a putative binding geometry. To our knowledge this is the first substantial test of an empiric...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1023/a:1008040323669
更新日期：1998-09-01 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：:Crystal structures of the 1,4-dihydropyridine (1,4-DHP) calcium channel activators Bay K 8643 [methyl 1,4-dihydro-2,6-dimethyl-3-nitro-4-(3-nitrophenyl)-pyridine-5-carboxy lat e], Bay O 8495 [methyl 1,4-dihydro-2,6-dimethyl-3-nitro-4-(3-trifluoromethylphenyl)-pyridine-5- carboxylate], and Bay O 9507 [methyl 1,4-dihydr...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/BF00129749
更新日期：1991-04-01 00:00:00
abstract：:Learning strategies can be used to improve the efficiency of virtual screening of very large databases. In these strategies new compounds to be screened are selected on the basis of the results obtained in previous stages, even if truly good ligands have not yet been identified. This approach requires that the scoring...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-008-9246-z
更新日期：2009-03-01 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：:The Drug Design Data Resource (D3R) ran Grand Challenge 2015 between September 2015 and February 2016. Two targets served as the framework to test community docking and scoring methods: (1) HSP90, donated by AbbVie and the Community Structure Activity Resource (CSAR), and (2) MAP4K4, donated by Genentech. The challeng...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-016-9946-8
更新日期：2016-09-01 00:00:00
