�All That Glitters Is Not Gold�: High-Resolution Crystal Structures of Ligand-Protein Complexes Need Not Always Represent Confident Binding Poses

Chakraborti, S and Hatti, K and Srinivasan, N (2021) �All That Glitters Is Not Gold�: High-Resolution Crystal Structures of Ligand-Protein Complexes Need Not Always Represent Confident Binding Poses. In: International Journal of Molecular Sciences, 22 (13).

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Abstract

Our understanding of the structure�function relationships of biomolecules and thereby applying it to drug discovery programs are substantially dependent on the availability of the structural information of ligand�protein complexes. However, the correct interpretation of the electron density of a small molecule bound to a crystal structure of a macromolecule is not trivial. Our analysis involving quality assessment of ~0.28 million small molecule�protein binding site pairs derived from crystal structures corresponding to ~66,000 PDB entries indicates that the majority (65) of the pairs might need little (54) or no (11) attention. Out of the remaining 35 of pairs that need attention, 11 of the pairs (including structures with high/moderate resolution) pose serious concerns. Unfortunately, most users of crystal structures lack the training to evaluate the quality of a crystal structure against its experimental data and, in general, rely on the resolution as a �gold standard� quality metric. Our work aims to sensitize the non-crystallographers that resolution, which is a global quality metric, need not be an accurate indicator of local structural quality. In this article, we demonstrate the use of several freely available tools that quantify local structural quality and are easy to use from a non-crystallographer�s perspective. We further propose a few solutions for consideration by the scientific community to promote quality research in structural biology and applied areas. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Item Type:	Journal Article
Publication:	International Journal of Molecular Sciences
Publisher:	MDPI AG
Additional Information:	The copyright for this article belongs to Authors
Department/Centre:	Division of Biological Sciences > Molecular Biophysics Unit
Date Deposited:	18 Aug 2021 07:48
Last Modified:	18 Aug 2021 07:48
URI:	http://eprints.iisc.ac.in/id/eprint/68999

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