Homo-timeric structural model of human microsomal prostaglandin E synthase-1 and characterization of its substrate/inhibitor binding interactions.

abstract：:4-(Phenylamino)-pyrrolo[2,1-f][1,2,4]triazines have been discovered as inhibitors of p38alpha. Experimental assays have proven that the configuration of alpha-Me-benzyl connected with amide at C6 is essential for the binding affinity. The S-configured inhibitor (11j) displays 80 times more potency than the R-configure...

journal_title：Journal of computer-aided molecular design

authors： Chen Q,Cui W,Ji M

更新日期：2009-10-01 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：:Understanding how proteins encode ligand specificity is fascinating and similar in importance to deciphering the genetic code. For protein-ligand recognition, the combination of an almost infinite variety of interfacial shapes and patterns of chemical groups makes the problem especially challenging. Here we analyze da...

journal_title：Journal of computer-aided molecular design

authors： Raschka S,Wolf AJ,Bemister-Buffington J,Kuhn LA

更新日期：2018-04-01 00:00:00

abstract：:A new and rigorous method for the fractional description of solvation and transfer free energies is presented. The method is based on the use of the Miertus-Scrocco-Tomasi self-consistent reaction field method (MST-SCRF), and allows for a rigorous partition of the total solvation free energy into surface elements. The...

journal_title：Journal of computer-aided molecular design

authors： Luque FJ,Barril X,Orozco M

更新日期：1999-03-01 00:00:00

abstract：:The Fas antigen, a cell surface receptor belonging to the tumor necrosis factor receptor (TNFR) superfamily, triggers programmed cell death (apoptosis) in the immune system. The three-dimensional structure of Fas and molecular details of the interaction between Fas and its ligand are currently unknown. A three-dimensi...

journal_title：Journal of computer-aided molecular design

authors： Bajorath J,Aruffo A

更新日期：1997-01-01 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：: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

authors： Klein C,Kaiser D,Kopp S,Chiba P,Ecker GF

更新日期：2002-11-01 00:00:00

abstract：:While it may seem intuitive that using an ensemble of multiple conformations of a receptor in structure-based virtual screening experiments would necessarily yield improved enrichment of actives relative to using just a single receptor, it turns out that at least in the p38 MAP kinase model system studied here, a very...

journal_title：Journal of computer-aided molecular design

authors： Rao S,Sanschagrin PC,Greenwood JR,Repasky MP,Sherman W,Farid R

更新日期：2008-09-01 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：: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：: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：: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 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：: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 a...

journal_title：Journal of computer-aided molecular design

authors： Bear S,Remers WA

更新日期：1996-04-01 00:00:00

abstract：:In the context of the SAMPL7 challenge, we computed, employing a non-equilibrium (NE) alchemical technique, the standard binding free energy of two series of host-guest systems, involving as a host the Isaac's TrimerTrip, a Cucurbituril-like open cavitand, and the Gilson's Cyclodextrin derivatives. The adopted NE alch...

journal_title：Journal of computer-aided molecular design

authors： Procacci P,Guarnieri G

更新日期：2021-01-04 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：:Mycobacterium tuberculosis (Mtb) 16.3 kDa heat shock protein 16.3 (HSP16.3) is a latency-associated antigen that can be targeted for latent tuberculosis (TB) diagnostic and therapeutic development. We have previously developed human VH domain antibodies (dAbs; clone E3 and F1) specific against HSP16.3. In this work, w...

journal_title：Journal of computer-aided molecular design

authors： Soong JX,Chan SK,Lim TS,Choong YS

更新日期：2019-03-01 00:00:00

abstract：:Toxoplasma (T.) gondii, the causative agent of toxoplasmosis, is a ubiquitous opportunistic pathogen that infects individuals worldwide, and is a leading cause of severe congenital neurologic and ocular disease in humans. No vaccine to protect humans is available, and hypersensitivity and toxicity limit the use of the...

journal_title：Journal of computer-aided molecular design

authors： Kortagere S,Mui E,McLeod R,Welsh WJ

更新日期：2011-05-01 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：: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：:Bradykinin (BK) is a member of the kinin family, released in response to inflammation, trauma, burns, shock, allergy and some cardiovascular diseases, provoking vasodilatation and increased vascular permeability among other effects. Their actions are mediated through at least two G-protein coupled receptors, B1 a rece...

journal_title：Journal of computer-aided molecular design

authors： Lupala CS,Gomez-Gutierrez P,Perez JJ

更新日期：2016-01-01 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

authors： McMartin C,Bohacek RS

更新日期：1997-07-01 00:00:00

abstract：:A set of algorithms designed to enhance the display of protein binding cavities is presented. These algorithms, collectively entitled CAVITY SEARCH, allow the user to isolate and fully define the extent of a particular cavity. Solid modeling techniques are employed to produce a detailed cast of the active site region,...

journal_title：Journal of computer-aided molecular design

authors： Ho CM,Marshall GR

更新日期：1990-12-01 00:00:00

abstract：:The preferential occurrence of certain disulphide-bridge topologies in proteins has prompted us to design a method and a program, KNOT-MATCH, for their classification. The program has been applied to a database of proteins with less than 65% homology and more than two disulphide bridges. We have investigated whether t...

journal_title：Journal of computer-aided molecular design

authors： Mas JM,Aloy P,Martí-Renom MA,Oliva B,de Llorens R,Avilés FX,Querol E

更新日期：2001-05-01 00:00:00

abstract：:In this paper we describe our approaches to predict the binding mode of twenty BACE1 ligands as part of Grand Challenge 4 (GC4), organized by the Drug Design Data Resource. Calculations for all submissions (except for one, which used AutoDock4.2) were performed using AutoDock-GPU, the new GPU-accelerated version of Au...

journal_title：Journal of computer-aided molecular design

authors： Santos-Martins D,Eberhardt J,Bianco G,Solis-Vasquez L,Ambrosio FA,Koch A,Forli S

更新日期：2019-12-01 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

authors： Schneider G,Lee ML,Stahl M,Schneider P

更新日期：2000-07-01 00:00:00

abstract：:This paper tests the performance of a simple empirical scoring function on a set of candidate designs produced by a de novo design package. The scoring function calculates approximate ligand-receptor binding affinities given a putative binding geometry. To our knowledge this is the first substantial test of an empiric...

journal_title：Journal of computer-aided molecular design

authors： Murray CW,Auton TR,Eldridge MD

更新日期：1998-09-01 00:00:00

abstract：:Water molecules in the binding pocket of a protein and their role in ligand binding have increasingly raised interest in recent years. Displacement of such water molecules by ligand atoms can be either favourable or unfavourable for ligand binding depending on the change in free enthalpy. In this study, we investigate...

journal_title：Journal of computer-aided molecular design

authors： Riniker S,Barandun LJ,Diederich F,Krämer O,Steffen A,van Gunsteren WF

更新日期：2012-12-01 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

authors： Lippert T,Schulz-Gasch T,Roche O,Guba W,Rarey M

更新日期：2011-10-01 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