Gossert, Alvar and Jahnke, Wolfgang (2016) NMR in drug discovery: A practical guide to identification and validation of ligands interacting with biological macromolecules. Progress in nuclear magnetic resonance spectroscopy, 97 (1). pp. 82-125. ISSN 00796565

Abstract

In this review, we cover NMR methods for identification and validation of ligands that interact with a biological macromolecule. Validation means making sure that the interaction is true, and initial binding effects from biophysical assays or activity readouts from biochemical assays were not just observed due to an experimental artifact. Out of scope of this review are methods for subsequent characterization of the interaction by quantitative KD determination, binding mode analysis, structure determination etc.
A plethora of NMR experiments is available for identification and validation of molecular interactions. We will focus on how to choose between different experiments and assess their strengths and liabilities. We introduce the concept of the validation cross, which helps to categorize experiments according to their information content and to simplify the choice of the right experiment in order to address a specific question. Additionally, we will provide the framework for drawing correct conclusions from experimental results in order to accurately evaluate such interactions.

Item Type:	Article
Date Deposited:	19 Nov 2016 00:45
Last Modified:	19 Nov 2016 00:45
URI:	https://oak.novartis.com/id/eprint/29048