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 of dopamine D4 agonists. The proximity of the dopamine D4 antagonist clozapine to the molecules of this series is also examined in the moment space.
journal_name
J Comput Aided Mol Desjournal_title
Journal of computer-aided molecular designauthors
Silverman BD,Pitman MC,Platt DE,Rigoutsos Idoi
10.1023/a:1008064003409subject
Has Abstractpub_date
1998-11-01 00:00:00pages
525-32issue
6eissn
0920-654Xissn
1573-4951journal_volume
12pub_type
杂志文章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::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
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::Structure-based drug design (SBDD) has matured within the last two decades as a valuable tool for the optimization of low molecular weight lead compounds to highly potent drugs. The key step in SBDD requires knowledge of the three-dimensional structure of the target-ligand complex, which is usually determined by X-ray...
journal_title:Journal of computer-aided molecular design
pub_type: 杂志文章
doi:10.1007/s10822-016-9966-4
更新日期:2016-09-01 00:00:00
abstract::RNA interference (RNAi) is a critical cellular pathway activated by double stranded RNA and regulates the gene expression of target mRNA. During RNAi, the 3' end of siRNA binds with the PAZ domain, followed by release and rebinding in a cyclic manner, which deemed essential for proper gene silencing. Recently, we prov...
journal_title:Journal of computer-aided molecular design
pub_type: 杂志文章
doi:10.1007/s10822-013-9665-3
更新日期:2013-07-01 00:00:00
abstract::Computational protein binding affinity prediction can play an important role in drug research but performing efficient and accurate binding free energy calculations is still challenging. In the context of phase 2 of the Drug Design Data Resource (D3R) Grand Challenge 2 we used our automated eTOX ALLIES approach to app...
journal_title:Journal of computer-aided molecular design
pub_type: 杂志文章
doi:10.1007/s10822-017-0055-0
更新日期:2018-01-01 00:00:00
abstract::The worldwide spread of beta-lactamases with hydrolytic activity extended to last resort carbapenems is aggravating the antibiotic resistance problem and endangers the successful antimicrobial treatment of clinically relevant pathogens. As recently highlighted by the World Health Organization, new strategies to contai...
journal_title:Journal of computer-aided molecular design
pub_type: 杂志文章
doi:10.1007/s10822-018-0182-2
更新日期:2019-02-01 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::Optimization in medicinal chemistry often involves designing replacements for a section of a molecule which aim to retain potency while improving other properties of the compound. In this study, we perform a retrospective analysis using a number of computational methods to identify active side chains amongst a pool of...
journal_title:Journal of computer-aided molecular design
pub_type: 杂志文章
doi:10.1007/s10822-020-00313-1
更新日期:2020-09-01 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::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::Multipoint interactions between synthetic and natural polymers provide a promising platform for many topical applications, including therapeutic blockage of virus-specific targets. Docking may become a useful tool for modelling of such interactions. However, the rigid docking cannot be correctly applied to synthetic p...
journal_title:Journal of computer-aided molecular design
pub_type: 杂志文章
doi:10.1007/s10822-012-9621-7
更新日期:2012-12-01 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::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::Hydrogen bonds are the most specific, and therefore predictable of the intermolecular interactions involved in ligand-protein binding. Given the structure of a molecule, it is possible to estimate the positions at which complementary hydrogen-bonding atoms could be found. Crystal-survey data are used in the design of ...
journal_title:Journal of computer-aided molecular design
pub_type: 杂志文章
doi:10.1023/a:1007900527102
更新日期:1997-05-01 00:00:00
abstract::The previously proposed models for the recognition and activation of 5-HT and histamine-H2 receptors, which were employed to explain the antagonist activity of LSD at both of these receptors, as well as the selective antagonism for H2 receptors by SKF-10856 and 9,10-dihydro-LSD, are used herein to design a compound to...
journal_title:Journal of computer-aided molecular design
pub_type: 杂志文章
doi:10.1007/BF00124342
更新日期:1991-06-01 00:00:00
abstract::Mycobacterium tuberculosis (Mtb) 16.3 kDa heat shock protein 16.3 (HSP16.3) is a latency-associated antigen that can be targeted for latent tuberculosis (TB) diagnostic and therapeutic development. We have previously developed human VH domain antibodies (dAbs; clone E3 and F1) specific against HSP16.3. In this work, w...
journal_title:Journal of computer-aided molecular design
pub_type: 杂志文章
doi:10.1007/s10822-019-00186-z
更新日期:2019-03-01 00:00:00
abstract::The Epstein-Barr Nuclear Antigen 1 (EBNA1) is a critical protein encoded by the Epstein-Barr Virus (EBV). During latent infection, EBNA1 is essential for DNA replication and transcription initiation of viral and cellular genes and is necessary to immortalize primary B-lymphocytes. Nonetheless, the concept of EBNA1 as ...
journal_title:Journal of computer-aided molecular design
pub_type: 杂志文章
doi:10.1007/s10822-016-9899-y
更新日期:2016-04-01 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 preferential occurrence of certain disulphide-bridge topologies in proteins has prompted us to design a method and a program, KNOT-MATCH, for their classification. The program has been applied to a database of proteins with less than 65% homology and more than two disulphide bridges. We have investigated whether t...
journal_title:Journal of computer-aided molecular design
pub_type: 杂志文章
doi:10.1023/a:1011164224144
更新日期:2001-05-01 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::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::Dengue and related flaviviruses represent a significant global health threat. The envelope glycoprotein E mediates virus attachment to a host cell and the subsequent fusion of viral and host cell membranes. The fusion process is driven by conformational changes in the E protein and is an essential step in the virus li...
journal_title:Journal of computer-aided molecular design
pub_type: 杂志文章
doi:10.1007/s10822-009-9263-6
更新日期:2009-06-01 00:00:00
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 implem...
journal_title:Journal of computer-aided molecular design
pub_type: 杂志文章
doi:10.1007/s10822-007-9110-6
更新日期:2007-05-01 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::In this work, the antimalarial activity of two series of 20 and 7 synthetic 1,2,4-trioxanes and a set of 20 cyclic peroxy ketals are tested for correlation search by means of Molecular Quantum Similarity Measures (MQSM). QSAR models, dealing with different biological responses (IC90, IC50 and ED90) of the parasite Pla...
journal_title:Journal of computer-aided molecular design
pub_type: 杂志文章
doi:10.1023/a:1015917510236
更新日期:2001-12-01 00:00:00
abstract::Glucokinase (GK) is involved in normal glucose homeostasis and therefore it is a valid target for drug design and discovery efforts. GK activators (GKAs) have excellent potential as treatments of hyperglycemia and diabetes. The combined recent interest in GKAs, together with docking limitations and shortages of dockin...
journal_title:Journal of computer-aided molecular design
pub_type: 杂志文章
doi:10.1007/s10822-014-9740-4
更新日期:2014-05-01 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::Chemical libraries contain thousands of compounds that need screening, which increases the need for computational methods that can rank or prioritize compounds. The tools of virtual screening are widely exploited to enhance the cost effectiveness of lead drug discovery programs by ranking chemical compounds databases ...
journal_title:Journal of computer-aided molecular design
pub_type: 杂志文章
doi:10.1007/s10822-016-0003-4
更新日期:2017-04-01 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