The structure-activity relationship of inhibitors of serotonin uptake and receptor binding.

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：: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

authors： Yennamalli R,Subbarao N,Kampmann T,McGeary RP,Young PR,Kobe B

更新日期：2009-06-01 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：:The binding mode prediction is of great importance to structure-based drug design. The discrimination of various binding poses of ligand generated by docking is a great challenge not only to docking score functions but also to the relatively expensive free energy calculation methods. Here we systematically analyzed th...

journal_title：Journal of computer-aided molecular design

authors： Liu K,Watanabe E,Kokubo H

更新日期：2017-02-01 00:00:00

abstract：:We have developed PLASS (Protein-Ligand Affinity Statistical Score), a pair-wise potential of mean-force for rapid estimation of the binding affinity of a ligand molecule to a protein active site. This scoring function is derived from the frequency of occurrence of atom-type pairs in crystallographic complexes taken f...

journal_title：Journal of computer-aided molecular design

authors： Ozrin VD,Subbotin MV,Nikitin SM

更新日期：2004-04-01 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

authors： Lomize AL,Pogozheva ID,Mosberg HI

更新日期：1999-07-01 00:00:00

abstract：:In the present work we have modeled the Michaelis complex of the cyclic-Adenosine Monophosphate Dependent (cAMD) Protein Kinase A (PKA) with Mg(2)ATP and the heptapeptide substrate Kemptide by classical molecular dynamics. The chosen synthetic substrate is relevant for its high efficiency and small size, and it has no...

journal_title：Journal of computer-aided molecular design

authors： Montenegro M,Garcia-Viloca M,González-Lafont A,Lluch JM

更新日期：2007-10-01 00:00:00

abstract：:Formyl-peptide receptors (FPRs) belong to the family A of the G-protein coupled receptor superfamily and include three subtypes: FPR, FPR-like-1 and FPR-like-2. They have been involved in the control of many inflammatory processes promoting the recruitment and infiltration of leukocytes in regions of inflammation thro...

journal_title：Journal of computer-aided molecular design

authors： Ferrari C,Macchiarulo A,Costantino G,Pellicciari R

更新日期：2006-05-01 00:00:00

abstract：:The "embedded cluster reference interaction site model" (EC-RISM) integral equation theory is applied to the problem of predicting aqueous pKa values for drug-like molecules based on an ensemble of tautomers. EC-RISM is based on self-consistent calculations of a solute's electronic structure and the distribution funct...

journal_title：Journal of computer-aided molecular design

authors： Tielker N,Eberlein L,Güssregen S,Kast SM

更新日期：2018-10-01 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：:In a previous paper, we have shown the utility of cluster analysis for identifying patterns in the way the C alpha atoms of fragments of the beta-turn are distributed in three dimensions. This work has been extended to the C alpha-C beta bond vectors of 2- and 3-side-chain fragments. Again, distinct patterns emerge an...

journal_title：Journal of computer-aided molecular design

authors： Garland SL,Dean PM

更新日期：1999-09-01 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

authors： Böhm HJ

更新日期：1998-07-01 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

authors： Bologa C,Allu TK,Olah M,Kappler MA,Oprea TI

更新日期：2005-09-01 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

authors： Kunimoto R,Bajorath J

更新日期：2017-09-01 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：:We used blind predictions of the 47 hydration free energies in the SAMPL4 challenge to test multiple partial charge models in the context of explicit solvent free energy simulations with the general AMBER force field. One of the partial charge models, IPolQ-Mod, is a fast continuum solvent-based implementation of the ...

journal_title：Journal of computer-aided molecular design

authors： Muddana HS,Sapra NV,Fenley AT,Gilson MK

更新日期：2014-03-01 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

authors： Sitzmann M,Ihlenfeldt WD,Nicklaus MC

更新日期：2010-06-01 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：: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：:The binding mode of (2S)-2-[4-[[(3S)-1-acetimidoyl-3-pyrrolidinyl]oxy]phenyl]-3-(7-ami dino-2- naphthyl)propanoic acid hydrochloride (DX-9065a, 4) to Factor Xa is examined using inhibition data for a series of analogs that have a hydrophobic group as well as basic or dibasic functionality. Comparative molecular field ...

journal_title：Journal of computer-aided molecular design

authors： Vaz RJ,McLean LR,Pelton JT

更新日期：1998-03-01 00:00:00

abstract：:Poly(amidoamine) (PAMAM) dendrimers have been extensively studied as delivery vectors in biomedical applications. A limited number of molecular dynamics (MD) simulation studies have investigated the effect of surface chemistry on therapeutic molecules loading, with the aim of providing insights for biocompatibility im...

journal_title：Journal of computer-aided molecular design

authors： Badalkhani-Khamseh F,Ebrahim-Habibi A,Hadipour NL

更新日期：2017-12-01 00:00:00

abstract：:Data driven decision making is a key element of today's pharmaceutical research, including early drug discovery. It comprises questions like which target to pursue, which chemical series to pursue, which compound to make next, or which compound to select for advanced profiling and promotion to pre-clinical development...

journal_title：Journal of computer-aided molecular design

authors： Beck B,Seeliger D,Kriegl JM

更新日期：2015-09-01 00:00:00

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：:As part of the fourth statistical assessment of modeling of proteins and ligands (sampl.eyesopen.com) prediction challenge, the strength of association of nine guests (1-9) binding to octa-acid host was determined by a combination of (1)H NMR and isothermal titration calorimetry. Association constants in sodium tetrab...

journal_title：Journal of computer-aided molecular design

authors： Gibb CL,Gibb BC

更新日期：2014-04-01 00:00:00

abstract：:The free fatty acid receptor 1 (FFAR1, formerly GPR40), is a potential G protein-coupled receptor (GPCR) target for the treatment of type 2 diabetes mellitus (T2DM), as it enhances glucose-dependent insulin secretion upon activation by endogenous long-chain free fatty acids. The presence of two allosterically communic...

journal_title：Journal of computer-aided molecular design

authors： Atanasio S,Deganutti G,Reynolds CA

更新日期：2020-11-01 00:00:00

abstract：:Chemical space networks (CSNs) have recently been introduced as an alternative to other coordinate-free and coordinate-based chemical space representations. In CSNs, nodes represent compounds and edges pairwise similarity relationships. In addition, nodes are annotated with compound property information such as biolog...

journal_title：Journal of computer-aided molecular design

authors： Zhang B,Vogt M,Maggiora GM,Bajorath J

更新日期：2015-10-01 00:00:00

abstract：:R67 dihydrofolate reductase (DHFR), a bacterial plasmid-encoded enzyme associated with resistance to the drug trimethoprim, shows neither sequence nor structural homology with the chromosomal DHFR. It presents a highly symmetrical toroidal structure, where four identical monomers contribute to the unique central activ...

journal_title：Journal of computer-aided molecular design

authors： Alonso H,Gillies MB,Cummins PL,Bliznyuk AA,Gready JE

更新日期：2005-03-01 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

authors： Della-Longa S,Arcovito A

更新日期：2015-01-01 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

authors： Stahl M,Todorov NP,James T,Mauser H,Boehm HJ,Dean PM

更新日期：2002-07-01 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