The use of docking-based comparative intermolecular contacts analysis to identify optimal docking conditions within glucokinase and to discover of new GK activators.

abstract：:Furanopyrimidine 1 (IC50 = 273 nM, LE = 0.36, LELP = 10.28) was recently identified by high-throughput screening (HTS) of an in-house library (125,000 compounds) as an Aurora kinase inhibitor. Structure-based hit optimization resulted in lead molecules with in vivo efficacy in a mouse tumour xenograft model, but no or...

journal_title：Journal of computer-aided molecular design

authors： Sarvagalla S,Singh VK,Ke YY,Shiao HY,Lin WH,Hsieh HP,Hsu JT,Coumar MS

更新日期：2015-01-01 00:00:00

abstract：:Using the X-ray crystal structure of the human topoisomerase I (top1) - DNA cleavable complex and the Sybyl software package, we have developed a general model for the ternary cleavable complex formed with four protoberberine alkaloids differing in the substitution on the terminal phenyl rings and covering a broad ran...

journal_title：Journal of computer-aided molecular design

authors： Kettmann V,Kost'álová D,Höltje HD

更新日期：2004-12-01 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

authors： Hansch C,Caldwell J

更新日期：1991-10-01 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

authors： Diller DJ,Merz KM Jr

更新日期：2002-02-01 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：: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

authors： Ignatov M,Liu C,Alekseenko A,Sun Z,Padhorny D,Kotelnikov S,Kazennov A,Grebenkin I,Kholodov Y,Kolosvari I,Perez A,Dill K,Kozakov D

更新日期：2019-01-01 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

authors： Padhorny D,Hall DR,Mirzaei H,Mamonov AB,Moghadasi M,Alekseenko A,Beglov D,Kozakov D

更新日期：2018-01-01 00:00:00

abstract：:Activity cliffs are formed by pairs or groups of structurally similar compounds with significant differences in potency. They represent a prominent feature of activity landscapes of compound data sets and a primary source of structure-activity relationship (SAR) information. Thus far, activity cliffs have only been co...

journal_title：Journal of computer-aided molecular design

authors： Hu Y,Maggiora GM,Bajorath J

更新日期：2013-02-01 00:00:00

abstract：:The Ligand Design (LUDI) approach has been used in order to design leucine aminopeptidase inhibitors, predict their activity and analyze their interactions with the enzyme. The investigation was based on the crystal structure of bovine lens leucine aminopeptidase (LAP) complexed with its inhibitor--the phosphonic acid...

journal_title：Journal of computer-aided molecular design

authors： Grembecka J,Sokalski WA,Kafarski P

更新日期：2000-08-01 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：: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

authors： Xu X,Yan C,Zou X

更新日期：2017-08-01 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

authors： Atlamazoglou V,Thireou T,Eliopoulos E

更新日期：2007-05-01 00:00:00

abstract：:The Multiple Copy Simultaneous Search methodology has been used to construct functionality maps for an extended region of human thrombin, including the active site. This method allows the determination of energetically favorable positions and orientations for functional groups defined by the user on the three-dimensio...

journal_title：Journal of computer-aided molecular design

authors： Grootenhuis PD,Karplus M

更新日期：1996-02-01 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

authors： Nikitina N,Ivashko E,Tchernykh A

更新日期：2018-02-01 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

authors： Kandeel M,Kitade Y

更新日期：2013-07-01 00:00:00

abstract：:A method is suggested to calculate improved entropies within the MM/PBSA approach (molecular mechanics combined with Poisson-Boltzmann and surface area calculations) to estimate protein-ligand binding affinities. In the conventional approach, the protein is truncated outside ~8 A from the ligand. This system is freely...

journal_title：Journal of computer-aided molecular design

authors： Kongsted J,Ryde U

更新日期：2009-02-01 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：: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

authors： Ehrman JN,Lim VT,Bannan CC,Thi N,Kyu DY,Mobley DL

更新日期：2021-01-28 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：: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

authors： Mills JE,Perkins TD,Dean PM

更新日期：1997-05-01 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

authors： Yakovenko O,Jones SJM

更新日期：2018-01-01 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

authors： Nagy P

更新日期：1988-04-01 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：:The kinase-regulatory cell signaling networks play a central role in the pathogenesis of human cervical cancer (hCC). However, only few kinase inhibitors have been successfully developed for treatment of this cancer to date. Considering that the active sites of protein kinases are highly conserved and small-molecule i...

journal_title：Journal of computer-aided molecular design

authors： Han M,Sun D

更新日期：2019-07-01 00:00:00

abstract：:Utilization of coupling constants as restraints in computational structure refinement is reviewed. In addition, we address the effect of conformational averaging and examine different approaches to apply the restraints when the experimental observable is obviously a result of averaging. Here, two different computation...

journal_title：Journal of computer-aided molecular design

authors： Mierke DF,Huber T,Kessler H

更新日期：1994-02-01 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：:Targeting Proviral integration-site of murine Moloney leukemia virus 1 kinase, hereafter called Pim-1 kinase, is a promising strategy for treating different kinds of human cancer. Headed for this a total list of 328 formerly reported Pim-1 kinase inhibitors has been explored and divided based on the pharmacophoric fea...

journal_title：Journal of computer-aided molecular design

authors： Shahin R,Swellmeen L,Shaheen O,Aboalhaija N,Habash M

更新日期：2016-01-01 00:00:00

abstract：:Recent progress in molecular biology has revealed that many non-coding RNAs regulate gene expression or catalyze biochemical reactions in tumors, viruses and several other diseases. The tertiary structure of RNA molecules and RNA-RNA/protein interaction sites are of increasing importance as potential targets for new m...

journal_title：Journal of computer-aided molecular design

authors： Yamasaki S,Amemiya T,Yabuki Y,Horimoto K,Fukui K

更新日期：2019-05-01 00:00:00

abstract：:Histo-blood group ABH antigens serve as recognition sites for infectious microorganisms and tissue lectins in intercellular communication, e.g. in tumor progression. Thus, they are of interest as a starting point for drug design. In this respect, potent non-hydrolysable derivatives such as thioglycosides are of specia...

journal_title：Journal of computer-aided molecular design

authors： Strino F,Lii JH,Gabius HJ,Nyholm PG

更新日期：2009-12-01 00:00:00

abstract：:In previous studies we have developed categorical QSAR models for predicting skin-sensitization potency based on 4D-fingerprint (4D-FP) descriptors and in vivo murine local lymph node assay (LLNA) measures. Only 4D-FP derived from the ground state (GMAX) structures of the molecules were used to build the QSAR models. ...

journal_title：Journal of computer-aided molecular design

authors： Liu J,Kern PS,Gerberick GF,Santos-Filho OA,Esposito EX,Hopfinger AJ,Tseng YJ

更新日期：2008-06-01 00:00:00