Next Article in Journal / Special Issue
Lead Discovery of Type II BRAF V600E Inhibitors Targeting the Structurally Validated DFG-Out Conformation Based upon Selected Fragments
Previous Article in Journal / Special Issue
Foreword: Pacific Fragments
Article Menu
Issue 7 (July) cover image

Export Article

Open AccessReview
Molecules 2016, 21(7), 854;

Process of Fragment-Based Lead Discovery—A Perspective from NMR

Hefei National Laboratory for Physical Science at the Microscale, School of Life Sciences, University of Science and Technology of China, Hefei 230027, Anhui, China
Author to whom correspondence should be addressed.
Academic Editors: Raymond S. Norton and Martin J. Scanlon
Received: 28 March 2016 / Revised: 22 May 2016 / Accepted: 24 May 2016 / Published: 16 July 2016
(This article belongs to the Special Issue Developments in Fragment-Based Lead Discovery)
Full-Text   |   PDF [2966 KB, uploaded 16 July 2016]   |  


Fragment-based lead discovery (FBLD) has proven fruitful during the past two decades for a variety of targets, even challenging protein–protein interaction (PPI) systems. Nuclear magnetic resonance (NMR) spectroscopy plays a vital role, from initial fragment-based screening to lead generation, because of its power to probe the intrinsically weak interactions between targets and low-molecular-weight fragments. Here, we review the NMR FBLD process from initial library construction to lead generation. We describe technical aspects regarding fragment library design, ligand- and protein-observed screening, and protein–ligand structure model generation. For weak binders, the initial hit-to-lead evolution can be guided by structural information retrieved from NMR spectroscopy, including chemical shift perturbation, transferred pseudocontact shifts, and paramagnetic relaxation enhancement. This perspective examines structure-guided optimization from weak fragment screening hits to potent leads for challenging PPI targets. View Full-Text
Keywords: fragment based lead discovery; NMR spectroscopy; protein–protein interaction fragment based lead discovery; NMR spectroscopy; protein–protein interaction

Graphical abstract

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

Share & Cite This Article

MDPI and ACS Style

Ma, R.; Wang, P.; Wu, J.; Ruan, K. Process of Fragment-Based Lead Discovery—A Perspective from NMR. Molecules 2016, 21, 854.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics



[Return to top]
Molecules EISSN 1420-3049 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top