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 was carried out using calculable chemical structure identifiers developed by the NCI CADD Group, based on hash codes available in the chemoinformatics toolkit CACTVS and a newly developed scoring scheme to define a canonical tautomer for any encountered structure. CACTVS's tautomerism definition, a set of 21 transform rules expressed in SMIRKS line notation, was used, which takes a comprehensive stance as to the possible types of tautomeric interconversion included. Tautomerism was found to be possible for more than 2/3 of the unique structures in the CSDB. A total of 680 million tautomers were calculated from, and including, the original structure records. Tautomerism overlap within the same individual database (i.e. at least one other entry was present that was really only a different tautomeric representation of the same compound) was found at an average rate of 0.3% of the original structure records, with values as high as nearly 2% for some of the databases in CSDB. Projected onto the set of unique structures (by FICuS identifier), this still occurred in about 1.5% of the cases. Tautomeric overlap across all constituent databases in CSDB was found for nearly 10% of the records in the collection.
journal_name
J Comput Aided Mol Desjournal_title
Journal of computer-aided molecular designauthors
Sitzmann M,Ihlenfeldt WD,Nicklaus MCdoi
10.1007/s10822-010-9346-4subject
Has Abstractpub_date
2010-06-01 00:00:00pages
521-51issue
6-7eissn
0920-654Xissn
1573-4951journal_volume
24pub_type
杂志文章abstract：:In a previous paper, we have shown the utility of cluster analysis for identifying patterns in the way the C alpha atoms of fragments of the beta-turn are distributed in three dimensions. This work has been extended to the C alpha-C beta bond vectors of 2- and 3-side-chain fragments. Again, distinct patterns emerge an...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1023/a:1008014620568
更新日期：1999-09-01 00:00:00
abstract：:Quantitative Structure-Activity Relationship (QSAR) models are used increasingly to screen chemical databases and/or virtual chemical libraries for potentially bioactive molecules. These developments emphasize the importance of rigorous model validation to ensure that the models have acceptable predictive power. Using...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1023/a:1025386326946
更新日期：2003-02-01 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：:Manifold representations of rotational/translational motion and conformational space of a ligand were previously shown to be effective for local energy optimization. In this paper we report the development of the Monte-Carlo energy minimization approach (MCM), which uses the same manifold representation. The approach ...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-018-0176-0
更新日期：2019-01-01 00:00:00
abstract：:Cytochrome P450 (CYP) enzymes play an important role in the metabolism of xenobiotics. Since they are connected to drug interactions, screening for potential inhibitors is of utmost importance in drug discovery settings. Our study provides an extensive classification model for P450-drug interactions with one of the mo...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-020-00308-y
更新日期：2020-08-01 00:00:00
abstract：:A method is suggested to calculate improved entropies within the MM/PBSA approach (molecular mechanics combined with Poisson-Boltzmann and surface area calculations) to estimate protein-ligand binding affinities. In the conventional approach, the protein is truncated outside ~8 A from the ligand. This system is freely...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-008-9238-z
更新日期：2009-02-01 00:00:00
abstract：:Feature selection is commonly used as a preprocessing step to machine learning for improving learning performance, lowering computational complexity and facilitating model interpretation. This paper proposes the application of boosting feature selection to improve the classification performance of standard feature sel...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-018-0171-5
更新日期：2018-11-01 00:00:00
abstract：:Two new computational tools, PRO_PHARMEX and PRO_SCOPE, for use in active-site-directed searching of 3D databases are described. PRO_PHARMEX is a flexible, graphics-based program facilitating the extraction of pharmacophores from the active site of a target macromolecule. These pharmacophores can then be used to searc...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/BF00124472
更新日期：1996-10-01 00:00:00
abstract：:An evolutionary algorithm was developed for fragment-based de novo design of molecules (TOPAS, TOPology-Assigning System). This stochastic method aims at generating a novel molecular structure mimicking a template structure. A set of approximately 25,000 fragment structures serves as the building block supply, which w...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1023/a:1008184403558
更新日期：2000-07-01 00:00:00
abstract：:Affinity chromatography is one of the most common techniques employed at the industrial-scale for antibody purification. In particular, the purification of human immunoglobulin G (hIgG) has gained relevance with the immobilization of its natural binding counterpart-Staphylococcus aureus Protein A (SpA) or with the rec...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-013-9703-1
更新日期：2014-01-01 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：:We have developed PLASS (Protein-Ligand Affinity Statistical Score), a pair-wise potential of mean-force for rapid estimation of the binding affinity of a ligand molecule to a protein active site. This scoring function is derived from the frequency of occurrence of atom-type pairs in crystallographic complexes taken f...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1023/b:jcam.0000046819.20241.16
更新日期：2004-04-01 00:00:00
abstract：:The Drug Design Data Resource (D3R) Grand Challenges present an opportunity to assess, in the context of a blind predictive challenge, the accuracy and the limits of tools and methodologies designed to help guide pharmaceutical drug discovery projects. Here, we report the results of our participation in the D3R Grand ...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-019-00249-1
更新日期：2020-02-01 00:00:00
abstract：:Several chiral vinylboranes have been theoretically evaluated as enantioselective Diels-Alder dienophiles. Theoretical results suggest that optically pure 2,5-diphenyl-1-vinyl-borolane should be the reagent of choice for performing such transformations efficiently. ...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1023/b:jcam.0000035200.30340.41
更新日期：2004-03-01 00:00:00
abstract：:A set of algorithms designed to enhance the display of protein binding cavities is presented. These algorithms, collectively entitled CAVITY SEARCH, allow the user to isolate and fully define the extent of a particular cavity. Solid modeling techniques are employed to produce a detailed cast of the active site region,...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/BF00117400
更新日期：1990-12-01 00:00:00
abstract：:The binding mode of (2S)-2-[4-[[(3S)-1-acetimidoyl-3-pyrrolidinyl]oxy]phenyl]-3-(7-ami dino-2- naphthyl)propanoic acid hydrochloride (DX-9065a, 4) to Factor Xa is examined using inhibition data for a series of analogs that have a hydrophobic group as well as basic or dibasic functionality. Comparative molecular field ...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1023/a:1007969517376
更新日期：1998-03-01 00:00:00
abstract：:Two new continuum solvation models have been presented recently, and in this paper they are explained and reviewed in detail with further examples. Solvation Model 2 (AM1-SM2) is based on the Austin Model 1 and Solvation Model 3 (PM3-SM3) on the Parameterized Model 3 semiempirical Hamiltonian. In addition to the incor...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/BF00126219
更新日期：1992-12-01 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：:In drug discovery, prediction of binding affinity ahead of synthesis to aid compound prioritization is still hampered by the low throughput of the more accurate methods and the lack of general pertinence of one method that fits all systems. Here we show the applicability of a method based on density functional theory ...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-015-9880-1
更新日期：2015-12-01 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：:In order to identify novel chemical classes of factor Xa inhibitors, five scoring functions (FlexX, DOCK, GOLD, ChemScore and PMF) were engaged to evaluate the multiple docking poses generated by FlexX. The compound collection was composed of confirmed potent factor Xa inhibitors and a subset of the LeadQuest screenin...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1023/b:jcam.0000047812.39758.ab
更新日期：2004-05-01 00:00:00
abstract：:A linear quantitative-structure activity relationship model is developed in this work using Multiple Linear Regression Analysis as applied to a series of 51 1-(3,3-diphenylpropyl)-piperidinyl phenylacetamides derivatives with CCR5 binding affinity. For the selection of the best variables the Elimination Selection-Step...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-006-9038-2
更新日期：2006-02-01 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：: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：:In this work the rigid-analogue approach has been used to obtain information on the active conformation(s) of the calcium antagonist verapamil. A series of semi-rigid analogues of verapamil were synthesized and their biological activities evaluated on guinea-pig heart and aorta. These molecules were analysed by means ...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/BF00119863
更新日期：1994-04-01 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
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：: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：:A new and rigorous method for the fractional description of solvation and transfer free energies is presented. The method is based on the use of the Miertus-Scrocco-Tomasi self-consistent reaction field method (MST-SCRF), and allows for a rigorous partition of the total solvation free energy into surface elements. The...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1023/a:1008036526741
更新日期：1999-03-01 00:00:00
abstract：:4-(Phenylamino)-pyrrolo[2,1-f][1,2,4]triazines have been discovered as inhibitors of p38alpha. Experimental assays have proven that the configuration of alpha-Me-benzyl connected with amide at C6 is essential for the binding affinity. The S-configured inhibitor (11j) displays 80 times more potency than the R-configure...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-009-9298-8
更新日期：2009-10-01 00:00:00
