Strategic approaches to drug design. II. Modelling studies on phosphodiesterase substrates and inhibitors.

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：:Two different types of approaches: (a) approaches that combine quantitative structure activity relationships, quantum mechanical electronic structure methods, and machine-learning and, (b) electronic structure vertical solvation approaches, were used to predict the logP coefficients of 11 molecules as part of the SAMP...

journal_title：Journal of computer-aided molecular design

authors： Patel P,Kuntz DM,Jones MR,Brooks BR,Wilson AK

更新日期：2020-05-01 00:00:00

abstract：:We employed a combination of molecular docking and dynamics to understand the interaction of three different radical scavengers (SB-HSC21, ABNM13 and trimidox) with ribonucleotide reductase M2 (hRRM2) domain. On the basis of the observed results, we can propose how these ligands interact with the enzyme, and cease the...

journal_title：Journal of computer-aided molecular design

authors： Basu A,Sinha BN

更新日期：2012-07-01 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：: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

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：:The establishment of quantitative structure-activity relationship (QSAR) models for the toxicity of polycylic aromatic hydrocarbons (PAHs) is described. Two properties, in vitro percutaneous absorption in rat skin and discrete levels of carcinogenic activity, are examined using molecular quantum similarity measures (M...

journal_title：Journal of computer-aided molecular design

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

更新日期：2001-01-01 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：: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：: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：: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：:A new method is presented for the calculation of the Molecular Electrostatic Potential (MEP) in large systems. Based on the mixed Quantum Mechanics/Molecular Mechanics (QM/MM) approach, the method assumes both a quantum and classical description for the molecule, and the calculation of the MEP in the space surrounding...

journal_title：Journal of computer-aided molecular design

authors： Hernández B,Luque FJ,Orozco M

更新日期：2000-05-01 00:00:00

abstract：:We have undertaken molecular dynamics simulations on the d(CGCAAAAAAGCG).d(CGCTTTTTTGCG) dodecamer in solution. In this study, we focus on aspects of conformation and dynamics, including the possibility of cross-strand hydrogen bonds. We compare our results with those from crystallography as well as infrared, Raman an...

journal_title：Journal of computer-aided molecular design

authors： de Souza ON,Goodfellow JM

更新日期：1994-06-01 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

authors： Czodrowski P

更新日期：2014-11-01 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

authors： Chau PL,Dean PM

更新日期：1992-08-01 00:00:00

abstract：:The acronym "CADD" is often used interchangeably to refer to "Computer Aided Drug Discovery" and "Computer Aided Drug Design". While the former definition implies the use of a computer to impact one or more aspects of discovering a drug, in this paper we contend that computational chemists are most effective when they...

journal_title：Journal of computer-aided molecular design

authors： Manas ES,Green DV

更新日期：2017-03-01 00:00:00

abstract：:The electron-conformational (EC) method in QSAR problems employs a unique (based on first principles) descriptor of molecular properties that incorporates the electronic structure and topology of the molecule and is presented in a digital-matrix form suitable for computer processing, the EC matrix of congruity (ECMC)....

journal_title：Journal of computer-aided molecular design

authors： Bersuker IB

更新日期：2008-06-01 00:00:00

abstract：:The project on crystallographic modelling aims at extending the application of interactive graphics to inorganic structures. Starting from the available expertise in organic and protein modelling, the symmetry of the crystal structure is used not only to draw fixed models of many unit cells of the structure, which as ...

journal_title：Journal of computer-aided molecular design

authors： Driessen RA,Loopstra BO,de Bruijn DP,Kuipers HP,Schenk H

更新日期：1988-10-01 00:00:00

abstract：:The V2 vasopressin renal receptor (V2R), which controls antidiuresis in mammals, is a member of the large family of heptahelical transmembrane (7TM) G protein-coupled receptors (GPCRs). Using the automated GPCR modeling facility available via Internet (http:/(/)expasy.hcuge.ch/swissmod/SWISS-MODEL.+ ++html) for constr...

journal_title：Journal of computer-aided molecular design

authors： Czaplewski C,Kaźmierkiewicz R,Ciarkowski J

更新日期：1998-05-01 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：:Chemical libraries contain thousands of compounds that need screening, which increases the need for computational methods that can rank or prioritize compounds. The tools of virtual screening are widely exploited to enhance the cost effectiveness of lead drug discovery programs by ranking chemical compounds databases ...

journal_title：Journal of computer-aided molecular design

authors： Al-Dabbagh MM,Salim N,Himmat M,Ahmed A,Saeed F

更新日期：2017-04-01 00:00:00

abstract：:All-atom molecular dynamics computer simulations were used to blindly predict the hydration free energies of a range of chloro-organic compounds as part of the SAMPL3 challenge. All compounds were parameterized within the framework of the OPLS-AA force field, using an established protocol to compute the absolute hydra...

journal_title：Journal of computer-aided molecular design

authors： Beckstein O,Iorga BI

更新日期：2012-05-01 00:00:00

abstract：:We describe the performance of multiple pose prediction methods for the D3R 2016 Grand Challenge. The pose prediction challenge includes 36 ligands, which represent 4 chemotypes and some miscellaneous structures against the FXR ligand binding domain. In this study we use a mix of fully automated methods as well as hum...

journal_title：Journal of computer-aided molecular design

authors： Fradera X,Verras A,Hu Y,Wang D,Wang H,Fells JI,Armacost KA,Crespo A,Sherborne B,Wang H,Peng Z,Gao YD

更新日期：2018-01-01 00:00:00

abstract：:The process of compound selection and prioritization is crucial for both combinatorial chemistry (CBC) and high throughput screening (HTS). Compound libraries have to be screened for unwanted chemical structures, as well as for unwanted chemical properties. Property extrema can be eliminated by using property filters,...

journal_title：Journal of computer-aided molecular design

authors： Oprea TI

更新日期：2000-03-01 00:00:00

abstract：:The use of MP2 level quantum mechanical (QM) calculations on isolated heteroaromatic ring systems for the prediction of the tautomeric propensities of whole molecules in a crystalline environment was examined. A Polarisable Continuum Model was used in the calculations to account for environment effects on the tautomer...

journal_title：Journal of computer-aided molecular design

authors： Cruz-Cabeza AJ,Schreyer A,Pitt WR

更新日期：2010-06-01 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：:For computational de novo design, a general retrospective validation work is a very challenging task. Here we propose a comprehensive workflow to de novo design driven by the needs of computational and medicinal chemists and, at the same time, we propose a general validation scheme for this technique. The study was co...

journal_title：Journal of computer-aided molecular design

authors： Zaliani A,Boda K,Seidel T,Herwig A,Schwab CH,Gasteiger J,Claussen H,Lemmen C,Degen J,Pärn J,Rarey M

更新日期：2009-08-01 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

authors： Gunner MR,Murakami T,Rustenburg AS,Işık M,Chodera JD

更新日期：2020-05-01 00:00:00

abstract：:Macroscopic pKa values were calculated for all compounds in the SAMPL6 blind prediction challenge, based on quantum chemical calculations with a continuum solvation model and a linear correction derived from a small training set. Microscopic pKa values were derived from the gas-phase free energy difference between pro...

journal_title：Journal of computer-aided molecular design

authors： Selwa E,Kenney IM,Beckstein O,Iorga BI

更新日期：2018-10-01 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