[NMR paper] Investigating the Dynamic Aspects of Drug-Protein Recognition through a Combination of MD and NMR Analyses: Implications for the Development of Protein-Protein Interaction Inhibitors.
Investigating the Dynamic Aspects of Drug-Protein Recognition through a Combination of MD and NMR Analyses: Implications for the Development of Protein-Protein Interaction Inhibitors.
Investigating the Dynamic Aspects of Drug-Protein Recognition through a Combination of MD and NMR Analyses: Implications for the Development of Protein-Protein Interaction Inhibitors.
PLoS One. 2014;9(5):e97153
Authors: Meli M, Pagano K, Ragona L, Colombo G
Abstract
In this paper, we investigate the dynamic aspects of the molecular recognition between a small molecule ligand and a flat, exposed protein surface, representing a typical target in the development of protein-protein interaction inhibitors. Specifically, we analyze the complex between the protein Fibroblast Growth Factor 2 (FGF2) and a recently discovered small molecule inhibitor, labeled sm27 for which the binding site and the residues mainly involved in small molecule recognition have been previously characterized. We have approached this problem using microsecond MD simulations and NMR-based characterizations of the dynamics of the apo and holo states of the system. Using direct combination and cross-validation of the results of the two techniques, we select the set of conformational states that best recapitulate the principal dynamic and structural properties of the complex. We then use this information to generate a multi-structure representation of the sm27-FGF2 interaction. We propose this kind of representation and approach as a useful tool in particular for the characterization of systems where the mutual dynamic influence between the interacting partners is expected to play an important role. The results presented can also be used to generate new rules for the rational expansion of the chemical diversity space of FGF2 inhibitors.
[NMR paper] Recent advances in protein NMR spectroscopy and their implications in protein therapeutics research.
Recent advances in protein NMR spectroscopy and their implications in protein therapeutics research.
Related Articles Recent advances in protein NMR spectroscopy and their implications in protein therapeutics research.
Anal Bioanal Chem. 2013 Dec 6;
Authors: Wang G, Zhang ZT, Jiang B, Zhang X, Li C, Liu M
Abstract
Nuclear magnetic resonance (NMR) spectroscopy and X-ray crystallography are the two main methods for protein three-dimensional structure determination at atomic resolution. According to the protein structures deposited in the...
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12-07-2013 01:00 PM
New Protein Evolution Insight Could Improve Drug Design - Drug Discovery & Development
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New Protein Evolution Insight Could Improve Drug Design
Drug Discovery & Development
The team used a variety of techniques to characterize the two versions of the enzyme, including X-ray crystallography and nuclear magnetic resonance, analyses of DHFR amino-acid sequences and evaluations of the enzyme's functionality in cells and in ...
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New Protein Evolution Insight Could Improve Drug Design - Drug Discovery & Development
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[NMR paper] Protein-Carbohydrate Interactions Studied by NMR. from Molecular Recognition to Drug Design.
Protein-Carbohydrate Interactions Studied by NMR. from Molecular Recognition to Drug Design.
Related Articles Protein-Carbohydrate Interactions Studied by NMR. from Molecular Recognition to Drug Design.
Curr Protein Pept Sci. 2012 Dec 10;
Authors: Fernandez-Alonso MD, Diaz D, Berbis MA, Marcelo F, Jimenez-Barbero J
Abstract
Diseases that result from infection are, in general, a consequence of specific interactions between a pathogenic organism and the cells. The study of host-pathogen interactions has provided insights for the design of...
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02-03-2013 10:22 AM
An evaluation tool for FKBP12-dependent and -independent mTOR inhibitors using a combination of FKBP-mTOR fusion protein, DSC and NMR.
An evaluation tool for FKBP12-dependent and -independent mTOR inhibitors using a combination of FKBP-mTOR fusion protein, DSC and NMR.
An evaluation tool for FKBP12-dependent and -independent mTOR inhibitors using a combination of FKBP-mTOR fusion protein, DSC and NMR.
Protein Eng Des Sel. 2011 Sep 6;
Authors: Sekiguchi M, Kobashigawa Y, Kawasaki M, Yokochi M, Kiso T, Suzumura KI, Mori K, Teramura T, Inagaki F
Abstract
Mammalian target of rapamycin (mTOR), a large multidomain protein kinase, regulates cell growth and metabolism in...
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09-09-2011 06:42 PM
Fluorine-Protein Interactions and (19)F NMR Isotropic Chemical Shifts: An Empirical Correlation with Implications for Drug Design.
Fluorine-Protein Interactions and (19)F NMR Isotropic Chemical Shifts: An Empirical Correlation with Implications for Drug Design.
Related Articles Fluorine-Protein Interactions and (19)F NMR Isotropic Chemical Shifts: An Empirical Correlation with Implications for Drug Design.
ChemMedChem. 2010 Nov 29;
Authors: Dalvit C, Vulpetti A
An empirical correlation between the fluorine isotropic chemical shifts, measured by (19)F NMR spectroscopy, and the type of fluorine-protein interactions observed in crystal structures is presented. The CF, CF(2), and...
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12-01-2010 04:41 PM
[NMR paper] NMR diffusion and relaxation study of drug-protein interaction.
NMR diffusion and relaxation study of drug-protein interaction.
Related Articles NMR diffusion and relaxation study of drug-protein interaction.
Spectrochim Acta A Mol Biomol Spectrosc. 1999 Aug;55A(9):1897-901
Authors: Luo RS, Liu ML, Mao XA
In this work, NMR diffusion and relaxation measurements are applied to the study of the interaction between the anti-inflammatory drug salicylate and the human serum albumin (HSA) in solutions. The self-diffusion coefficients and the spin-lattice relaxation rates of salicylate are measured as a function...
Investigating the Dynamic Aspects of Drug-Protein Recognition through a Combination of MD and NMR Analyses: Implications for the Development of Protein-Protein Interaction Inhibitors.
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