Issue 1, 2023

Fragment screening libraries for the identification of protein hot spots and their minimal binding pharmacophores

Abstract

Fragment-based drug design relies heavily on structural information for the elaboration and optimisation of hits. The ability to identify neighbouring binding hot spots, energetically favourable interactions and conserved binding motifs in protein structures through X-ray crystallography can inform the evolution of fragments into lead-like compounds through structure-based design. The composition of fragment libraries can be designed and curated to fit this purpose and herein, we describe and compare screening libraries containing compounds comprising between 2 and 18 heavy atoms. We evaluate the properties of the compounds in these libraries and assess their ability to probe protein surfaces for binding hot spots.

Graphical abstract: Fragment screening libraries for the identification of protein hot spots and their minimal binding pharmacophores

Supplementary files

Article information

Article type
Research Article
Submitted
30 Jul 2022
Accepted
11 Nov 2022
First published
29 Nov 2022

RSC Med. Chem., 2023,14, 135-143

Author version available

Fragment screening libraries for the identification of protein hot spots and their minimal binding pharmacophores

R. L. Whitehouse, W. S. Alwan, O. V. Ilyichova, A. J. Taylor, I. R. Chandrashekaran, B. Mohanty, B. C. Doak and M. J. Scanlon, RSC Med. Chem., 2023, 14, 135 DOI: 10.1039/D2MD00253A

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