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, carbon-to-carbon connections, and distances between the carbons. Two-dimensional 13C-13C COSY and 2D slices from the distance dimension of the 3D-connectivity matrix were used to produce a relationship among the 2D spectral patterns for polychlorinated dibenzofurans, dibenzodioxins, and biphenyls (PCDFs, PCDDs, and PCBs respectively) binding to the aryl hydrocarbon receptor (AhR). We refer to this technique as comparative structural connectivity spectral analysis (CoSCoSA) modeling. All CoSCoSA models were developed using forward multiple linear regression analysis of the predicted 13C NMR structure-connectivity spectral bins. A CoSCoSA model for 26 PCDFs had an explained variance (r2) of 0.93 and an average leave-four-out cross-validated variance (q(2)4) of 0.89. A CoSCoSA model for 14 PCDDs produced an r2 of 0.90 and an average leave-two-out cross-validated variance (q(2)2) of 0.79. One CoSCoSA model for 12 PCBs gave an r2 of 0.91 and an average q(2)2 of 0.80. Another CoSCoSA model for all 52 compounds had an r2 of 0.85 and an average q(2)2 of 0.52. Major benefits of CoSCoSA modeling include ease of development since the technique does not use molecular docking routines.
journal_name
J Comput Aided Mol Desjournal_title
Journal of computer-aided molecular designauthors
Beger RD,Buzatu DA,Wilkes JGdoi
10.1023/a:1022479510524subject
Has Abstractpub_date
2002-10-01 00:00:00pages
727-40issue
10eissn
0920-654Xissn
1573-4951journal_volume
16pub_type
杂志文章abstract：:A new computer program is described, which positions small molecules into clefts of protein structures (e.g. an active site of an enzyme) in such a way that hydrogen bonds can be formed with the enzyme and hydrophobic pockets are filled with hydrophobic groups. The program works in three steps. First it calculates int...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/BF00124387
更新日期：1992-02-01 00:00:00
abstract：:The use of a recently proposed hydrophobic similarity index for the alignment of molecules and the prediction of their differences in biological activity is described. The hydrophobic similarity index exploits atomic contributions to the octanol/water transfer free energy, which are evaluated by means of the fractiona...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-005-7928-3
更新日期：2005-06-01 00:00:00
abstract：:Babesia bigemina is a protozoan parasite that causes babesiosis, a disease with a world-wide distribution in mammals, principally affecting cattle and man. The unveiling of the genome of B. bigemina is a project in active progress that has already revealed a number of new targets with potential interest for the design...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-013-9682-2
更新日期：2013-09-01 00:00:00
abstract：:There is a need for improved and generally applicable scoring functions for fragment-based approaches to ligand design. Here, we evaluate the performance of a computationally efficient model for inhibitory activity estimation, which is composed only of multipole electrostatic energy and dispersion energy terms that ap...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-017-0035-4
更新日期：2017-08-01 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：: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：: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 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：:Many molecular simulation methods use force fields to help model and simulate molecules and their behavior in various environments. Force fields are sets of functions and parameters used to calculate the potential energy of a chemical system as a function of the atomic coordinates. Despite the widespread use of force ...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-020-00367-1
更新日期：2021-01-28 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：:Quantitative Structure-Activity Relationship (QSAR) models are critical in various areas of drug discovery, for example in lead optimisation and virtual screening. Recently, the need for models that are not only predictive but also interpretable has been highlighted. In this paper, a new methodology is proposed to bui...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-019-00228-6
更新日期：2019-09-01 00:00:00
abstract：:Folate receptor α (FRα) is a cell surface, glycophosphatidylinositol-anchored protein which has focussed attention as a therapeutic target and as a marker for the diagnosis of cancer. It has a high affinity for the dietary supplemented folic acid (FOL), carrying out endocytic transport across the cell membrane and del...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-014-9801-8
更新日期：2015-01-01 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：:Capacity ratio (log k') values, which are a measure of hydrophobicity, were calculated directly from the three-dimensional structures of 17 furans and 54 triazines using the comparative molecular field analysis approach. The H2O probe and the GRID force field, including hydrogen-bond potentials, yielded excellent corr...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/BF00125172
更新日期：1995-08-01 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：:As part of the fourth statistical assessment of modeling of proteins and ligands (sampl.eyesopen.com) prediction challenge, the strength of association of nine guests (1-9) binding to octa-acid host was determined by a combination of (1)H NMR and isothermal titration calorimetry. Association constants in sodium tetrab...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-013-9690-2
更新日期：2014-04-01 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：:We employed a combination of molecular docking and dynamics to understand the interaction of three different radical scavengers (SB-HSC21, ABNM13 and trimidox) with ribonucleotide reductase M2 (hRRM2) domain. On the basis of the observed results, we can propose how these ligands interact with the enzyme, and cease the...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-012-9581-y
更新日期：2012-07-01 00:00:00
abstract：:An empirical hydrophobic field-like 3D function has been calculated with the program HINT (hydrophobic interactions) and imported into the SYBYL implementation of CoMFA (Comparative Molecular Field Analysis). The addition of hydrophobicity appears to offer increased chemical interpretability of CoMFA models. An exampl...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/BF00135313
更新日期：1991-12-01 00:00:00
abstract：:A new type of shape descriptor is proposed to describe the spatial orientation for non-covalent interactions. It is built from simple, anisotropic Gaussian contributions that are parameterised by 10 adjustable values. The descriptors have been used to fit propensity distributions derived from scatter data stored in th...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1023/a:1008109717641
更新日期：2000-11-01 00:00:00
abstract：:A theoretical conformational study was performed on leu-enkephalin in its zwitterionic form, both in vacuo and in the presence of a number, n, of up to 13 water molecules saturating its first hydration shell. The intramolecular energy of enkephalin as well as the intermolecular enkephalin-water and water-water interac...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/BF00129748
更新日期：1991-04-01 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：:Lipophilicity, often expressed as distribution coefficients (log D) in octanol/water, is an important physicochemical parameter influencing processes such as oral absorption, brain uptake and various pharmacokinetic (PK) properties. Increasing log D values increases oral absorption, plasma protein binding and volume o...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章,评审
doi：10.1023/a:1008192010023
更新日期：2001-03-01 00:00:00
abstract：:We have developed quantitative structure-activity relationship (QSAR) models for 44 non-nucleoside HIV-1 reverse transcriptase inhibitors (NNRTIs) of the pyridinone derivative type. The k nearest neighbor (kNN) variable selection approach was used. This method utilizes multiple descriptors such as molecular connectivi...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-005-4789-8
更新日期：2005-04-01 00:00:00
abstract：:Clarithromycin (6-O-methylerythromycin A) is a 14-membered macrolide antibiotic which is active in vitro against clinically important gram-positive and gram-negative bacteria. The selectivity of the methylation of the C-6 OH group is studied on erythromycin A derivatives. To understand the effect of the solvent on the...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1023/b:jcam.0000030037.67742.cb
更新日期：2004-02-01 00:00:00
abstract：:We report the implementation of molecular modeling approaches developed as a part of the 2016 Grand Challenge 2, the blinded competition of computer aided drug design technologies held by the D3R Drug Design Data Resource ( https://drugdesigndata.org/ ). The challenge was focused on the ligands of the farnesoid X rece...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-017-0085-7
更新日期：2018-01-01 00:00:00
abstract：:In the recent SAMPL5 challenge, participants submitted predictions for cyclohexane/water distribution coefficients for a set of 53 small molecules. Distribution coefficients (log D) replace the hydration free energies that were a central part of the past five SAMPL challenges. A wide variety of computational methods w...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-016-9954-8
更新日期：2016-11-01 00:00:00
abstract：:In this paper we describe our approaches to predict the binding mode of twenty BACE1 ligands as part of Grand Challenge 4 (GC4), organized by the Drug Design Data Resource. Calculations for all submissions (except for one, which used AutoDock4.2) were performed using AutoDock-GPU, the new GPU-accelerated version of Au...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-019-00241-9
更新日期：2019-12-01 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：:Water molecules in the binding pocket of a protein and their role in ligand binding have increasingly raised interest in recent years. Displacement of such water molecules by ligand atoms can be either favourable or unfavourable for ligand binding depending on the change in free enthalpy. In this study, we investigate...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-012-9620-8
更新日期：2012-12-01 00:00:00
