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 the AT1 receptor. Consistency with the previously derived activity models was always checked to contemporarily test the validity of the various hypotheses. The specific conformations chosen for the study, the procedures invoked to superimpose all structures, the conditions employed to generate steric and electrostatic field values and the various PCA/PLS runs are discussed in detail. The effect of experimental design techniques to select objects (molecules) and variables (descriptors) with respect to the predictive power of the QSAR models derived was especially analysed.
journal_name
J Comput Aided Mol Desjournal_title
Journal of computer-aided molecular designauthors
Belvisi L,Bravi G,Catalano G,Mabilia M,Salimbeni A,Scolastico Cdoi
10.1007/BF00134180subject
Has Abstractpub_date
1996-12-01 00:00:00pages
567-82issue
6eissn
0920-654Xissn
1573-4951journal_volume
10pub_type
杂志文章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：: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：:In the present work we have modeled the Michaelis complex of the cyclic-Adenosine Monophosphate Dependent (cAMD) Protein Kinase A (PKA) with Mg(2)ATP and the heptapeptide substrate Kemptide by classical molecular dynamics. The chosen synthetic substrate is relevant for its high efficiency and small size, and it has no...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-007-9143-x
更新日期：2007-10-01 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 one-dimensional model of Hann et al. (JChem Inf Comput Sci 41(3):856–864) has been extended to include reverse binding and wrap-around interaction modes between the protein and ligand to explore the complete combinatorial matrix of molecular recognition. The cumulative distribution function of the Maxwell–Boltzman...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-013-9683-1
更新日期：2013-09-01 00:00:00
abstract：:Pamidronate, alendronate, APHBP and neridronate are a group of drugs, known as second-generation bisphosphonates (2G-BPs), commonly used in the treatment of bone-resorption disorders, and recently their use has been related to some collateral side effects. The therapeutic activity of 2G-BPs is related to the inhibitio...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-017-0034-5
更新日期：2017-07-01 00:00:00
abstract：:Two different types of approaches: (a) approaches that combine quantitative structure activity relationships, quantum mechanical electronic structure methods, and machine-learning and, (b) electronic structure vertical solvation approaches, were used to predict the logP coefficients of 11 molecules as part of the SAMP...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-020-00287-0
更新日期：2020-05-01 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：: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：:Estimation of bioavailability and toxicity at the very beginning of the drug development process is one of the big challenges in drug discovery. Most of the processes involved in ADME are driven by rather unspecific interactions between drugs and biological macromolecules. Within the past decade, drug transport pumps ...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1023/a:1023828527638
更新日期：2002-11-01 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：: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：: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：: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：: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：:The support vector machine, which is a novel algorithm from the machine learning community, was used to develop quantitation and classification models which can be used as a potential screening mechanism for a novel series of COX-2 selective inhibitors. Each compound was represented by calculated structural descriptor...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-004-2722-1
更新日期：2004-06-01 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：:In virtual drug screening, the chemical diversity of hits is an important factor, along with their predicted activity. Moreover, interim results are of interest for directing the further research, and their diversity is also desirable. In this paper, we consider a problem of obtaining a diverse set of virtual screenin...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-017-0093-7
更新日期：2018-02-01 00:00:00
abstract：:The linear finite difference Poisson-Boltzmann (FDPB) equation is applied to the calculation of the electrostatic binding free energies of a group of inhibitors to the Neuraminidase enzyme. An ensemble of enzyme-inhibitor complex conformations was generated using Monte Carlo simulations and the electrostatic binding f...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1023/a:1008197913568
更新日期：2001-02-01 00:00:00
abstract：:We have derived a model of the nicotinic acetylcholine binding site. This was accomplished by using three known agonists (acetylcholine, nicotine and epibatidine) as templates around which polypeptide side chains, found to be part of the receptor cavity from published molecular biology studies, are allowed to flow fre...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1023/a:1008029924865
更新日期：1999-01-01 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：: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：: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：:A novel computational Diels-Alderase design, based on a relatively rare form of carboxylesterase from Geobacillus stearothermophilus, is presented and theoretically evaluated. The structure was found by mining the PDB for a suitable oxyanion hole-containing structure, followed by a combinatorial approach to find suita...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-012-9601-y
更新日期：2012-09-01 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：: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：:The project on crystallographic modelling aims at extending the application of interactive graphics to inorganic structures. Starting from the available expertise in organic and protein modelling, the symmetry of the crystal structure is used not only to draw fixed models of many unit cells of the structure, which as ...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/BF01531996
更新日期：1988-10-01 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：:The recent outbreak of the respiratory syndrome-related coronavirus (SARS-CoV-2) is stimulating an unprecedented scientific campaign to alleviate the burden of the coronavirus disease (COVID-19). One line of research has focused on targeting SARS-CoV-2 proteins fundamental for its replication by repurposing drugs appr...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-020-00356-4
更新日期：2020-10-26 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
