Abstract：
:Intercalative binding of the antitumor drugs amonafide and azonafide to the oligonucleotide duplex d(GGCCGGCCGG).d(CCGGCCGGCC) was compared using molecular dynamics in vacuum with the AMBER force field. A number of reasonable possible binding conformations were obtained, with the azonafide complexes favored over the amonafide complexes in net binding enthalpy. In comparison with amonafide, the larger chromophore of azonafide permits greater DNA distortion and wider side-chain swings, without falling out of the intercalation site. The best model obtained was used for further dynamics on amonafide and azonafide with solvent and counterions present, and again the azonafide complex had a more favorable enthalpy. Furthermore, the enthalpy change on going from solvent into the intercalation site was less unfavorable for azonafide. These results are consistent with the stronger DNA binding of azonafide compared to amonafide, as observed in relative melting transition temperature increases and tumor inhibition in cell cultures.
journal_name
J Comput Aided Mol Desjournal_title
Journal of computer-aided molecular designauthors
Bear S,Remers WAdoi
10.1007/BF00402824subject
Has Abstractpub_date
1996-04-01 00:00:00pages
165-75issue
2eissn
0920-654Xissn
1573-4951journal_volume
10pub_type
杂志文章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：: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：: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：: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 bacterial ribosome is a major target of naturally occurring thiopeptides antibiotics. Studying thiopeptide (e.g. thiostrepton) binding to the GAR's 23S·L11 ribosomal subunit using docking methods is challenging. Regarding the target, the binding site is composed of a flexible protein-RNA nonbonded interface whose ...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-014-9797-0
更新日期：2014-12-01 00:00:00
abstract：:In the 1960s, the kappa statistic was introduced for the estimation of chance agreement in inter- and intra-rater reliability studies. The kappa statistic was strongly pushed by the medical field where it could be successfully applied via analyzing diagnoses of identical patient groups. Kappa is well suited for classi...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-014-9759-6
更新日期：2014-11-01 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：:We have used virtual screening to develop models for the binding of aryl substituted heterocycles to p38α MAPK. Virtual screening was conducted on a number of p38α MAPK crystal structures using a library of 46 known p38α MAPK inhibitors containing a heterocyclic core substituted by pyridine and fluorophenyl rings (str...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-012-9569-7
更新日期：2012-04-01 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
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：: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：:Patents from medicinal chemistry represent a rich source of novel compounds and activity data that appear only infrequently in the scientific literature. Moreover, patent information provides a primary focal point for drug discovery. Accordingly, text mining and image extraction approaches have become hot topics in pa...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-017-0061-2
更新日期：2017-09-01 00:00:00
abstract：:De novo ligand design supports the search for novel molecular scaffolds in medicinal chemistry projects. This search can either be based on structural information of the targeted active site (structure-based approach) or on similarity to known binders (ligand-based approach). In the absence of structural information o...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-011-9473-6
更新日期：2011-10-01 00:00:00
abstract：:We examined "descriptor collision" for several chemical fingerprint systems (MDL 320, Daylight, SMDL), and for a 2D-based descriptor set. For large databases (ChemNavigator and WOMBAT), the smallest collision rate remains around 5%. We systematically increase the "descriptor collision" rate (here termed "descriptor co...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-005-9020-4
更新日期：2005-09-01 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：:In this paper a database of small frequently occurring molecular fragments is used for the determination of fragment bond lengths from the Cambridge Structural Database. A large number of bond types are described that have not been reported previously. ...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/BF00125946
更新日期：1992-08-01 00:00:00
abstract：:Electrostatic potential complementarity between ligands and their receptor sites is evaluated by the superposition of the electrostatic potential, generated by the receptor, onto the ligand potential over the ligand van der Waals surface. We would like to examine which structural factors generate this pattern of super...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/BF00123665
更新日期：1994-10-01 00:00:00
abstract：:In the absence of a 3D structure of the target biomolecule, to propose the 3D requirements for a small molecule to exhibit a particular bioactivity, one must supply both a bioactive conformation and a superposition rule for every active compound. Our strategy identifies both simultaneously. We first generate and optim...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/BF00141577
更新日期：1993-02-01 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：: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：: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：:Fast Fourier transform (FFT) based approaches have been successful in application to modeling of relatively rigid protein-protein complexes. Recently, we have been able to adapt the FFT methodology to treatment of flexible protein-peptide interactions. Here, we report our latest attempt to expand the capabilities of t...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-017-0069-7
更新日期：2018-01-01 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：: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：: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：: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：:The de novo design program Skelgen has been used to design inhibitor structures for four targets of pharmaceutical interest. The designed structures are compared to modeled binding modes of known inhibitors (i) visually and (ii) by means of a novel similarity measure considering the size and spatial proximity of the m...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1023/a:1021242018286
更新日期：2002-07-01 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：:The pKa is the standard measure used to describe the aqueous proton affinity of a compound, indicating the proton concentration (pH) at which two protonation states (e.g. A- and AH) have equal free energy. However, compounds can have additional protonation states (e.g. AH2+), and may assume multiple tautomeric forms, ...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-020-00280-7
更新日期：2020-05-01 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
