Related ArticlesStructure-based design of scaffolds targeting PDE10A by INPHARMA-NMR.
J Chem Inf Model. 2017 May 31;:
Authors: Codutti L, Grimaldi M, Carlomagno T
Abstract
Phosphodiesterases (PDE) hydrolyze both cyclic AMP and GMP (cAMP/cGMP) and are responsible for the regulation of their levels in a multitude of cellular functions. PDE10A is expressed in the brain and is a validated target for both schizophrenia and Huntington disease. Here, we address the identification of novel chemical scaffolds that may bind PDE10A via structure-based drug design. For this task, we use INPHARMA, an NMR-based method that measures protein-mediated interligand NOEs between pairs of weakly, competitively binding ligands. INPHARMA is applied to a combination of four chemically diverse PDE10A binding fragments, with the aim of merging their pharmacophoric features into a larger, tighter binding molecule. All four ligands bind the PDE10A cAMP binding domain with affinity in the micromolar range. The application of INPHARMA to identify the correct docking poses of these ligands is challenging due to the nature of the binding pocket and the high content of water mediated intermolecular contacts. Nevertheless, ensemble docking in the presence of conserved water molecules generates docking poses that are in agreement with all sets of INPHARMA data. These poses are used to build a pharmacophore model with which we search the ZINC database.
PMID: 28569061 [PubMed - as supplied by publisher]
[NMR paper] NMR approaches in structure-based lead discovery: Recent developments and new frontiers for targeting multi-protein complexes.
NMR approaches in structure-based lead discovery: Recent developments and new frontiers for targeting multi-protein complexes.
Related Articles NMR approaches in structure-based lead discovery: Recent developments and new frontiers for targeting multi-protein complexes.
Prog Biophys Mol Biol. 2014 Aug 28;
Authors: Dias DM, Ciulli A
Abstract
Nuclear magnetic resonance (NMR) spectroscopy is a pivotal method for structure-based and fragment-based lead discovery because it is one of the most robust techniques to provide information...
nmrlearner
Journal club
0
09-02-2014 11:17 PM
NMR approaches in structure-based lead discovery: Recent developments and new frontiers for targeting multi-protein complexes
NMR approaches in structure-based lead discovery: Recent developments and new frontiers for targeting multi-protein complexes
Publication date: Available online 28 August 2014
Source:Progress in Biophysics and Molecular Biology</br>
Author(s): David M. Dias , Alessio Ciulli</br>
Nuclear magnetic resonance (NMR) spectroscopy is a pivotal method for structure-based and fragment-based lead discovery because it is one of the most robust techniques to provide information on protein structure, dynamics and interaction at an atomic level in solution. Nowadays, in most...
nmrlearner
Journal club
0
08-29-2014 05:36 PM
[NMR paper] Structure-based drug design: NMR-based approach for ligand-protein interactions.
Structure-based drug design: NMR-based approach for ligand-protein interactions.
Related Articles Structure-based drug design: NMR-based approach for ligand-protein interactions.
Drug Discov Today Technol. 2006;3(3):241-5
Authors: Zhang X, Tang H, Ye C, Liu M
Abstract
The realization of the powerfulness in analyzing ligand-protein interactions at the atomic resolution has made NMR techniques increasingly attractive in drug discovery and development. With some significant new method developments during the past few years,...
nmrlearner
Journal club
0
07-06-2014 08:28 PM
Structure-Based Drug Design
Structure-Based Drug Design
http://www.spectroscopynow.com/common/images/thumbnails/no_img.gifThe 13th Structure-Based Drug Discovery conference will feature the development of in silico technology as well as experimental approaches useful for accurately predicting and modeling the structures of proteins in structure-based drug design efforts.
More...
nmrlearner
Conferences
0
05-22-2013 04:43 PM
Postdoctoral Fellow in structure-based drug design by NMR ...
Postdoctoral Fellow in structure-based drug design by NMR ...
Postdoctoral Fellow in structure-based drug design by NMR, Heidelberg, Germany. View all science jobs and scientific careers from Nature Jobs, the premier ...
www.nature.com/.../241001-Postdoctoral-Fellow-in-structure-...
More...
nmrlearner
Job marketplace
0
01-15-2012 04:04 AM
Design and NMR Studies of Cyclic Peptides Targeting the N-Terminal Domain of the Protein Tyrosine Phosphatase YopH.
Design and NMR Studies of Cyclic Peptides Targeting the N-Terminal Domain of the Protein Tyrosine Phosphatase YopH.
Design and NMR Studies of Cyclic Peptides Targeting the N-Terminal Domain of the Protein Tyrosine Phosphatase YopH.
Chem Biol Drug Des. 2010 Nov 30;
Authors: Leone M, Barile E, Dahl R, Pellecchia M
We report on the design and evaluation of novel cyclic peptides targeting the N-terminal domain of the protein tyrosine phosphatase YopH from Yersinia. Cyclic peptides have been designed based on a short sequence from the protein SKAP-HOM...
nmrlearner
Journal club
0
12-02-2010 02:54 PM
[NMR paper] NMR spectroscopy in structure-based drug design.
NMR spectroscopy in structure-based drug design.
http://www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--linkinghub.elsevier.com-ihub-images-PubMedLink.gif Related Articles NMR spectroscopy in structure-based drug design.
Curr Opin Biotechnol. 1999 Feb;10(1):42-7
Authors: Roberts GC
NMR methods for the study of motion in proteins continue to improve, and a number of studies of protein-ligand complexes relevant to drug design have been reported over the past year, for example, studies of fatty-acid-binding protein and SH2 and SH3 domains. These...
Structure-based design of scaffolds targeting PDE10A by INPHARMA-NMR.
Linear Mode
