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-structure conformer distributions and the calculated potential-energy differences, even though the calculations relate to a gas-phase environment. Torsion angles associated with high strain energy (> 1 kcal mol-1) appear to be very unusual in crystal structures and, in general, high-energy conformers are underrepresented in crystal structures compared with a gas-phase, room-temperature Boltzmann distribution. It is concluded that crystal packing effects rarely have a strong systematic effect on molecular conformations. Therefore, the conformational distribution of a molecular substructure in a series of related crystal structures is likely to be a good guide to the corresponding gas-phase potential energy surface.
journal_name
J Comput Aided Mol Desjournal_title
Journal of computer-aided molecular designauthors
Allen FH,Harris SE,Taylor Rdoi
10.1007/BF00355046subject
Has Abstractpub_date
1996-06-01 00:00:00pages
247-54issue
3eissn
0920-654Xissn
1573-4951journal_volume
10pub_type
杂志文章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::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
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journal_title:Journal of computer-aided molecular design
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更新日期:2019-01-01 00:00:00
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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::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::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
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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::A dataset of 82 protein-ligand complexes of known 3D structure and binding constant Ki was analysed to elucidate the important factors that determine the strength of protein-ligand interactions. The following parameters were investigated: the number and geometry of hydrogen bonds and ionic interactions between the pro...
journal_title:Journal of computer-aided molecular design
pub_type: 杂志文章,评审
doi:10.1023/a:1007999920146
更新日期:1998-07-01 00:00:00
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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
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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
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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::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
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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::In contrast to the computational generation of conventional tautomers, the analogous operation that would produce ring-chain tautomers is rarely available in cheminformatics codes. This is partly due to the perceived unimportance of ring-chain tautomerism and partly because specialized algorithms are required to reali...
journal_title:Journal of computer-aided molecular design
pub_type: 杂志文章
doi:10.1007/s10822-020-00334-w
更新日期:2020-08-24 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::The similarity between Plasmodium falciparum phosphodiesterase enzymes (PfPDEs) and their human counterparts have been examined and human PDE9A was found to be a suitable template for the construction of homology models for each of the four PfPDE isoforms. In contrast, the architecture of the active sites of each mode...
journal_title:Journal of computer-aided molecular design
pub_type: 杂志文章
doi:10.1007/s10822-011-9458-5
更新日期:2011-08-01 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::The use of MP2 level quantum mechanical (QM) calculations on isolated heteroaromatic ring systems for the prediction of the tautomeric propensities of whole molecules in a crystalline environment was examined. A Polarisable Continuum Model was used in the calculations to account for environment effects on the tautomer...
journal_title:Journal of computer-aided molecular design
pub_type: 杂志文章
doi:10.1007/s10822-010-9345-5
更新日期:2010-06-01 00:00:00
abstract::An analysis of five different datasets of inhibitors of serotonin uptake has yielded quantitative structure/activity relationships (QSARs) which delineate the role of steric and hydrophobic properties essential for inhibition by phenylethylamine-type analogues. ...
journal_title:Journal of computer-aided molecular design
pub_type: 杂志文章
doi:10.1007/BF00125664
更新日期:1991-10-01 00:00:00
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journal_title:Journal of computer-aided molecular design
pub_type: 杂志文章
doi:10.1023/b:jcam.0000004622.13865.4f
更新日期:2003-08-01 00:00:00
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journal_title:Journal of computer-aided molecular design
pub_type: 杂志文章
doi:10.1023/a:1008197913568
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journal_title:Journal of computer-aided molecular design
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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::The liver is extremely vulnerable to the effects of xenobiotics due to its critical role in metabolism. Drug-induced hepatotoxicity may involve any number of different liver injuries, some of which lead to organ failure and, ultimately, patient death. Understandably, liver toxicity is one of the most important dose-li...
journal_title:Journal of computer-aided molecular design
pub_type: 杂志文章
doi:10.1023/b:jcam.0000021834.50768.c6
更新日期:2003-12-01 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
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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::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
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journal_title:Journal of computer-aided molecular design
pub_type: 杂志文章
doi:10.1007/s10822-019-00211-1
更新日期:2019-07-01 00:00:00
abstract::Overexpression of Bcl-2 and Bcl-xL proteins, both inhibitors of apoptosis or programmed cell death, is related to the generation and development of several types of cancer as well as to an elevated resistance to chemotherapeutic treatments. Given that synthetic peptide fragments of the BH3 domain are capable to bind t...
journal_title:Journal of computer-aided molecular design
pub_type: 杂志文章
doi:10.1023/b:jcam.0000022559.72848.1c
更新日期:2004-01-01 00:00:00
abstract::A new method is presented for the calculation of the Molecular Electrostatic Potential (MEP) in large systems. Based on the mixed Quantum Mechanics/Molecular Mechanics (QM/MM) approach, the method assumes both a quantum and classical description for the molecule, and the calculation of the MEP in the space surrounding...
journal_title:Journal of computer-aided molecular design
pub_type: 杂志文章
doi:10.1023/a:1008111820916
更新日期:2000-05-01 00:00:00