Nuclear magnetic resonance (NMR) spectroscopy has contributed to structure-based drug development (SBDD) in a unique way compared to the other biophysical methods. The potency of a ligand binding to a protein is dictated by the binding free energy, which is an intricate interplay between entropy and enthalpy. In addition to providing the atomic resolution structural information, NMR can help to identify proteinâ??ligand interactions that potentially contribute to the enthalpic component of the free energy. NMR can also illuminate dynamic aspects of the interaction, which correspond to the entropic term of the free energy. The ability of NMR to access both terms in the free energy equation stems from the suite of experiments developed to shed light on various aspects that contribute to both entropy and enthalpy, deepening our understanding of the biological function of macromolecules and assisting to target them in physiological conditions. Here we provide a brief account of the contribution of NMR to SBDD, highlighting hallmark examples and discussing the challenges that demand further method development. In the era of integrated biology, the unique ability of NMR to directly ascertain structural and dynamical aspects of macromolecule and monitor changes in these properties upon engaging a ligand can be combined with computational and other structural and biophysical methods to provide a more complete picture of the energetics of drug engagement with the target. Such efforts can be used to engineer better drugs.
Structure of A2aAR protein holds clues for better drug design - Drug Target Review
Structure of A2aAR protein holds clues for better drug design - Drug Target Review
Structure of A2aAR protein holds clues for better drug design Drug Target ReviewScientists have investigated a key protein used in drug design and discovered dynamic structural features that may lead to new ways to target diseases…
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01-07-2019 05:49 AM
New Structure of Key Protein Holds Clues for Better Drug Design - Drug Discovery & Development
New Structure of Key Protein Holds Clues for Better Drug Design - Drug Discovery & Development
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New Structure of Key Protein Holds Clues for Better Drug Design
Drug Discovery & Development
To solve this problem, the researchers used a technique called nuclear magnetic resonance (NMR) spectroscopy, which creates strong magnetic fields to locate the positions of probes in a sample. Wüthrich is a...
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01-29-2018 01:57 PM
Structure of A2aAR protein holds clues for better drug design - Drug Target Review
Structure of A2aAR protein holds clues for better drug design - Drug Target Review
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Drug Target Review
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Structure of A2aAR protein holds clues for better drug design
Drug Target Review
A2aAR protein holds clues for better drug design. Scientists have investigated a key protein used in drug design and discovered dynamic structural features that may lead to new ways to target diseases.
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01-03-2018 08:43 AM
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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10-01-2013 09:43 AM
[NMR paper] NMR investigations of structural and dynamics features of natively unstructured drug peptide - salmon calcitonin: implication to rational design of potent sCT analogs.
NMR investigations of structural and dynamics features of natively unstructured drug peptide - salmon calcitonin: implication to rational design of potent sCT analogs.
http://www.bionmr.com//www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--media.wiley.com-assets-2250-98-WileyOnlineLibrary-Button_120x27px_FullText.gif Related Articles NMR investigations of structural and dynamics features of natively unstructured drug peptide - salmon calcitonin: implication to rational design of potent sCT analogs.
J Pept Sci. 2013 Jan;19(1):33-45
Authors: Rawat A, Kumar D
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06-07-2013 10:04 AM
The dark energy of proteins comes to light: conformational entropy and its role in protein function revealed by NMR relaxation
The dark energy of proteins comes to light: conformational entropy and its role in protein function revealed by NMR relaxation
Available online 13 December 2012
Publication year: 2012
Source:Current Opinion in Structural Biology</br>
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Historically it has been virtually impossible to experimentally determine the contribution of residual protein entropy to fundamental protein activities such as the binding of ligands. Recent progress has illuminated the possibility of employing NMR relaxation methods to quantitatively determine the role of changes in conformational...
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02-03-2013 10:13 AM
[NMR paper] Role of entropy in protein thermostability: folding kinetics of a hyperthermophilic c
Role of entropy in protein thermostability: folding kinetics of a hyperthermophilic cold shock protein at high temperatures using 19F NMR.
Related Articles Role of entropy in protein thermostability: folding kinetics of a hyperthermophilic cold shock protein at high temperatures using 19F NMR.
Biochemistry. 2002 Oct 1;41(39):11670-80
Authors: Schuler B, Kremer W, Kalbitzer HR, Jaenicke R
We used (19)F NMR to extend the temperature range accessible to detailed kinetic and equilibrium studies of a hyperthermophilic protein. Employing an...
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[NMR paper] NMR relaxation studies of the role of conformational entropy in protein stability and
NMR relaxation studies of the role of conformational entropy in protein stability and ligand binding.
Related Articles NMR relaxation studies of the role of conformational entropy in protein stability and ligand binding.
Acc Chem Res. 2001 May;34(5):379-88
Authors: Stone MJ
Recent advances in the measurement and analysis of protein NMR relaxation data have made it possible to characterize the dynamical properties of many backbone and side chain groups. With certain caveats, changes in flexibility that occur upon ligand binding, mutation, or...
The role of NMR in leveraging dynamics and entropy in drug design
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