Semi-rigid analogues of the calcium antagonist verapamil: a molecular modelling study.

abstract：:The Drug Design Data Resource (D3R) ran Grand Challenge 2015 between September 2015 and February 2016. Two targets served as the framework to test community docking and scoring methods: (1) HSP90, donated by AbbVie and the Community Structure Activity Resource (CSAR), and (2) MAP4K4, donated by Genentech. The challeng...

journal_title：Journal of computer-aided molecular design

authors： Gathiaka S,Liu S,Chiu M,Yang H,Stuckey JA,Kang YN,Delproposto J,Kubish G,Dunbar JB Jr,Carlson HA,Burley SK,Walters WP,Amaro RE,Feher VA,Gilson MK

更新日期：2016-09-01 00:00:00

abstract：:Anaplastic lymphoma kinase (ALK) has been thought to be a prospective target of anti-drug resistance design in treatment of tumors and specific neuron diseases. It is highly useful for the seeking of possible strategy alleviating drug resistance to probe the mutation-mediated effect on binding of inhibitors to ALK. In...

journal_title：Journal of computer-aided molecular design

authors： Chen J,Wang W,Sun H,Pang L,Yin B

更新日期：2020-12-01 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：: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：: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：:Feature selection is commonly used as a preprocessing step to machine learning for improving learning performance, lowering computational complexity and facilitating model interpretation. This paper proposes the application of boosting feature selection to improve the classification performance of standard feature sel...

journal_title：Journal of computer-aided molecular design

authors： Cerruela García G,García-Pedrajas N

更新日期：2018-11-01 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：: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：: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：:Computational protein binding affinity prediction can play an important role in drug research but performing efficient and accurate binding free energy calculations is still challenging. In the context of phase 2 of the Drug Design Data Resource (D3R) Grand Challenge 2 we used our automated eTOX ALLIES approach to app...

journal_title：Journal of computer-aided molecular design

authors： Rifai EA,van Dijk M,Vermeulen NPE,Geerke DP

更新日期：2018-01-01 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：:ERG-associated protein with the SET domain (ESET/SET domain bifurcated 1/SETDB1/KMT1E) is a histone lysine methyltransferase (HKMT) and it preferentially tri-methylates lysine 9 of histone H3 (H3K9me3). SETDB1/ESET leads to heterochromatin condensation and epigenetic gene silencing. These functional changes are report...

journal_title：Journal of computer-aided molecular design

authors： Park I,Hwang YJ,Kim T,Viswanath ANI,Londhe AM,Jung SY,Sim KM,Min SJ,Lee JE,Seong J,Kim YK,No KT,Ryu H,Pae AN

更新日期：2017-10-01 00:00:00

abstract：:Molecular modeling techniques and three-dimensional (3D) pattern analysis have been used to investigate the chemical and steric properties of compounds that inhibit transport of the plant hormone auxin. These compounds bind to a specific site on the plant plasma membrane characterized by its affinity for the herbicide...

journal_title：Journal of computer-aided molecular design

authors： Bures MG,Black-Schaefer C,Gardner G

更新日期：1991-08-01 00:00:00

abstract：:The conformational preferences of 12 molecular substructures in the crystalline state have been determined and compared with those predicted for relevant model compounds by ab initio molecular orbital calculations. Least-squares regression shows that there is a statistically significant correlation between the crystal...

journal_title：Journal of computer-aided molecular design

authors： Allen FH,Harris SE,Taylor R

更新日期：1996-06-01 00:00:00

abstract：:The interaction mechanism of triazolyl substituted tetrahydrobenzofuran derivatives (compound 1 (N, N-Dipropyl-1-(2-phenyl-4,5,6,7-tetrahydrobenzofuran-4-yl)-1H-1,2,3-triazole-4-methanamine) and 2 (1-(2-Phenyl-4,5,6,7-tetrahydrobenzofuran-4-yl)-4-(morpholin-4-ylmethyl)-1H-1,2,3-triazole)) with H(+),K(+)-ATPase at diff...

journal_title：Journal of computer-aided molecular design

authors： Luo HJ,Wang JZ,Huang NY,Deng WQ,Zou K

更新日期：2016-01-01 00:00:00

abstract：:Pharmacophore methods provide a way of establishing a structure activity relationship for a series of known active ligands. Often, there are several plausible hypotheses that could explain the same set of ligands and, in such cases, it is important that the chemist is presented with alternatives that can be tested wit...

journal_title：Journal of computer-aided molecular design

authors： Cottrell SJ,Gillet VJ,Taylor R,Wilton DJ

更新日期：2004-11-01 00:00:00

abstract：:AstexViewer is a Java molecular graphics program that can be used for visualisation in many aspects of structure-based drug design. This paper describes its functionality, implementation and examples of its use. The program can run as an Applet in a web browser allowing structures to be displayed without installing ad...

journal_title：Journal of computer-aided molecular design

authors： Hartshorn MJ

更新日期：2002-12-01 00:00:00

abstract：:Inducible, microsomal prostaglandin E synthase 1 (mPGES-1), the terminal enzyme in the prostaglandin (PG) biosynthetic pathway, constitutes a promising therapeutic target for the development of new anti-inflammatory drugs. To elucidate structure-function relationships and to enable structure-based design, an mPGES-1 h...

journal_title：Journal of computer-aided molecular design

authors： Xing L,Kurumbail RG,Frazier RB,Davies MS,Fujiwara H,Weinberg RA,Gierse JK,Caspers N,Carter JS,McDonald JJ,Moore WM,Vazquez ML

更新日期：2009-01-01 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：: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：:Ligand efficiency metrics are used in drug discovery to normalize biological activity or affinity with respect to physicochemical properties such as lipophilicity and molecular size. This Perspective provides an overview of ligand efficiency metrics and summarizes thermodynamics of protein-ligand binding. Different cl...

journal_title：Journal of computer-aided molecular design

authors： Kenny PW,Leitão A,Montanari CA

更新日期：2014-07-01 00:00:00

abstract：:Electrostatic potential complementarity between ligands and their receptor sites is evaluated by the superposition of the electrostatic potential, generated by the receptor, onto the ligand potential over the ligand van der Waals surface. We would like to examine which structural factors generate this pattern of super...

journal_title：Journal of computer-aided molecular design

authors： Chau PL,Dean PM

更新日期：1994-10-01 00:00:00

abstract：:Cheminformatics protocols have been developed and assessed that identify a small set of fragments which can represent the compounds in a chemical library for use in fragment-based ligand discovery. Six different methods have been implemented and tested on Input Libraries of compounds from three suppliers. The resultin...

journal_title：Journal of computer-aided molecular design

authors： Schulz MN,Landström J,Bright K,Hubbard RE

更新日期：2011-07-01 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：:Structure-based drug design (SBDD) has matured within the last two decades as a valuable tool for the optimization of low molecular weight lead compounds to highly potent drugs. The key step in SBDD requires knowledge of the three-dimensional structure of the target-ligand complex, which is usually determined by X-ray...

journal_title：Journal of computer-aided molecular design

authors： Salmaso V,Sturlese M,Cuzzolin A,Moro S

更新日期：2016-09-01 00:00:00

abstract：:Quantitative Structure-Activity Relationship (QSAR) models are critical in various areas of drug discovery, for example in lead optimisation and virtual screening. Recently, the need for models that are not only predictive but also interpretable has been highlighted. In this paper, a new methodology is proposed to bui...

journal_title：Journal of computer-aided molecular design

authors： Cardoso-Silva J,Papageorgiou LG,Tsoka S

更新日期：2019-09-01 00:00:00

abstract：:Here, we report our results from quantitative structure-activity relationship studies on tyrosinase inhibitors. Interactions between benzoic acid derivatives and tyrosinase active sites were also studied using a molecular docking method. These studies indicated that one possible mechanism for the interaction between b...

journal_title：Journal of computer-aided molecular design

authors： Xue CB,Luo WC,Ding Q,Liu SZ,Gao XX

更新日期：2008-05-01 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：: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：: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