Computational studies of new potential antimalarial compounds--stereoelectronic complementarity with the receptor.

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

authors： Nissink JWM,Verdonk ML,Klebe G

更新日期：2000-11-01 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

authors： Pinto M,Perez JJ,Rubio-Martinez J

更新日期：2004-01-01 00:00:00

abstract：:Non-canonical base pairs contribute immensely to the structural and functional variability of RNA, which calls for a detailed characterization of their spatial conformation. Intra-base pair parameters, namely propeller, buckle, open-angle, stagger, shear and stretch describe structure of base pairs indicating planarit...

journal_title：Journal of computer-aided molecular design

authors： Mukherjee S,Bansal M,Bhattacharyya D

更新日期：2006-10-01 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

authors： Martin YC,Bures MG,Danaher EA,DeLazzer J,Lico I,Pavlik PA

更新日期：1993-02-01 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

authors： Gianti E,Messick TE,Lieberman PM,Zauhar RJ

更新日期：2016-04-01 00:00:00

abstract：:Recently, we reported structurally novel PDE4 inhibitors based on 1,4-benzodiazepine derivatives. The main interest in developing bezodiazepine-based PDE4 inhibitors is in their lack of adverse effects of emesis with respect to rolipram-like compounds. A large effort has thus been made toward the structural optimizati...

journal_title：Journal of computer-aided molecular design

authors： Ducrot P,Andrianjara CR,Wrigglesworth R

更新日期：2001-09-01 00:00:00

abstract：:The design of molecules with desired properties is still a challenge because of the largely unpredictable end results. Computational methods can be used to assist and speed up this process. In particular, genetic algorithms have proved to be powerful tools with a wide range of applications, e.g. in the field of drug d...

journal_title：Journal of computer-aided molecular design

authors： Kamphausen S,Höltge N,Wirsching F,Morys-Wortmann C,Riester D,Goetz R,Thürk M,Schwienhorst A

更新日期：2002-08-01 00:00:00

abstract：:Several chiral vinylboranes have been theoretically evaluated as enantioselective Diels-Alder dienophiles. Theoretical results suggest that optically pure 2,5-diphenyl-1-vinyl-borolane should be the reagent of choice for performing such transformations efficiently. ...

journal_title：Journal of computer-aided molecular design

authors： Pellegrinet SC,Silva MA,Goodman JM

更新日期：2004-03-01 00:00:00

abstract：:When we build a predictive model of a drug property we rigorously assess its predictive accuracy, but we are rarely able to address the most important question, "How useful will the model be in making a decision in a practical context?" To answer this requires an understanding of the prior probability distribution ("t...

journal_title：Journal of computer-aided molecular design

authors： Segall M,Chadwick A

更新日期：2010-12-01 00:00:00

abstract：:Both society and industry are interested in increasing the safety of pharmaceuticals. Potentially dangerous compounds could be filtered out at early stages of R&D by computer prediction of biological activity and ADMET characteristics. Accuracy of such predictions strongly depends on the quality & quantity of informat...

journal_title：Journal of computer-aided molecular design

authors： Filimonov D,Poroikov V

更新日期：2005-09-01 00:00:00

abstract：:A combined strategy based on the development of pharmacophore hypotheses and NMR approaches is reported for the identification of novel inhibitors of heparanase, a key enzyme involved in tumor metastasis through the remodeling of the subepithelial and subendothelial basement membranes, resulting in the dissemination o...

journal_title：Journal of computer-aided molecular design

authors： Gozalbes R,Mosulén S,Carbajo RJ,Pineda-Lucena A

更新日期：2009-08-01 00:00:00

abstract：:Computational techniques, such as Quantitative Structure-Property Relationship (QSPR) modeling, are very useful in predicting physicochemical properties of various chemicals. Building QSPR models requires calculating molecular descriptors and the proper choice of the geometry optimization method, which will be dedicat...

journal_title：Journal of computer-aided molecular design

authors： Rybinska A,Sosnowska A,Barycki M,Puzyn T

更新日期：2016-02-01 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

authors： Cheng A,Dixon SL

更新日期：2003-12-01 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

authors： Cincilla G,Vidal D,Pons M

更新日期：2009-03-01 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

authors： Nilar SH,Ma NL,Keller TH

更新日期：2013-09-01 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

authors： Demetropoulos IN,Gresh N

更新日期：1991-04-01 00:00:00

abstract：:Drug discovery is an expensive and time-consuming process. To make this process more efficient quantum chemistry methods can be employed. The electrophilicity index is one property that can be calculated by quantum chemistry methods, and if calculated correctly gives insight into the reactivity of covalent inhibitors....

journal_title：Journal of computer-aided molecular design

authors： Hermann MR,Pautsch A,Grundl MA,Weber A,Tautermann CS

更新日期：2020-10-05 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

authors： Kellogg GE,Semus SF,Abraham DJ

更新日期：1991-12-01 00:00:00

abstract：:The mounting evidences have shown that signal transducer and activator of transcription 3 (Stat3) is a critical target for cancer therapy. Recently, we developed a G-quartet oligonucleotide T40214 as a novel and potent Stat3 inhibitor. T40214 specifically inhibited DNA-binding activity of Stat3 and significantly suppr...

journal_title：Journal of computer-aided molecular design

authors： Zhu Q,Jing N

更新日期：2007-10-01 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

authors： Medina-Franco JL,Golbraikh A,Oloff S,Castillo R,Tropsha A

更新日期：2005-04-01 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

authors： Campagne F,Jestin R,Reversat JL,Bernassau JM,Maigret B

更新日期：1999-11-01 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

authors： Tsvetkov VB,Serbin AV

更新日期：2012-12-01 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

authors： Woods CJ,King MA,Essex JW

更新日期：2001-02-01 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

authors： Nascimento ÉCM,Oliva M,Andrés J

更新日期：2018-05-01 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

authors： Roos K,Hogner A,Ogg D,Packer MJ,Hansson E,Granberg KL,Evertsson E,Nordqvist A

更新日期：2015-12-01 00:00:00

abstract：:A method has been developed that allows one to drive a molecule to conformations of lowest energy given the starting conformation, the identity of the rotatable bonds and the step size. This method has proved useful in our hands in the drug design arena where it is frequently more important to get 'low-energy' conform...

journal_title：Journal of computer-aided molecular design

authors： Jaeger EP,Peterson ML,Treasurywala AM

更新日期：1995-02-01 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

authors： Gironés X,Gallegos A,Carbó-Dorca R

更新日期：2001-12-01 00:00:00

abstract：:In this work, we present a case study to explore the challenges associated with finding novel molecules for a receptor that has been studied in depth and has a wealth of chemical information available. Specifically, we apply a previously described protocol that incorporates explicit water molecules in the ligand bindi...

journal_title：Journal of computer-aided molecular design

authors： Lenselink EB,Beuming T,van Veen C,Massink A,Sherman W,van Vlijmen HW,IJzerman AP

更新日期：2016-10-01 00:00:00

abstract：:We present blind predictions submitted to the SAMPL5 challenge on calculating distribution coefficients. The predictions were based on estimating the solvation free energies in water and cyclohexane of the 53 compounds in the challenge. These free energies were computed using alchemical free energy simulations based o...

journal_title：Journal of computer-aided molecular design

authors： Genheden S,Essex JW

更新日期：2016-11-01 00:00:00

abstract：:To generate reduced point charge models of proteins, we developed an original approach to hierarchically locate extrema in charge density distribution functions built from the Poisson equation applied to smoothed molecular electrostatic potential (MEP) functions. A charge fitting program was used to assign charge valu...

journal_title：Journal of computer-aided molecular design

authors： Leherte L,Vercauteren DP

更新日期：2011-10-01 00:00:00