Nadzirin, N. | Search bioRxiv

bioRxiv2023

PDBe CCDUtils: an RDKit-based toolkit for handling and analysing small molecules in the Protein Data Bank

While the Protein Data Bank (PDB) contains a wealth of structural information on ligands bound to macromolecules, their analysis can be challenging due to the large amount and diversity of data. Here, we present PDBe CCDUtils, a versatile toolkit for processing and analysing small molecules from the PDB in PDBx/mmCIF format. PDBe CCDUtils provides streamlined access to all the metadata for small molecules in the PDB and offers a set of convenient methods to compute various properties using RDKit, such as 2D depictions, 3D conformers, physicochemical properties, scaffolds, common fragments and cross-references to small molecule databases using UniChem. The toolkit also provides methods for identifying all the covalently attached chemical components in a macromolecular structure and calculating similarity among small molecules. By providing a broad range of functionality, PDBe CCDUtils caters to the needs of researchers in cheminformatics, structural biology, bioinformatics and computational chemistry.

bioinformatics↗

bioRxiv2023

Identifying Protein Conformational States in the PDB and Comparison to AlphaFold2 Predictions

Proteins, as molecular machines, are necessarily dynamic macromolecules that carry out essential cellular functions. Recognising their stable conformations is important for understanding the molecular mechanisms of disease. While AI-based computational methods have enabled protein structure prediction, the prediction of protein dynamics remains a challenge. Here, we present a deterministic pipeline that clusters experimentally determined protein structures to comprehensively recognise conformational states across the Protein Data Bank. Our approach clusters protein chains based on a GLObal CONformation (GLOCON) difference score, which is computed from pairwise C-alpha distances. By superposing the clustered structures, differences and similarities in conformational states can be observed. Additionally, we offer users the ability to superpose predicted models from the AlphaFold Database to the clusters of PDB structures. This clustering pipeline significantly advances researchers ability to explore the conformational landscape within the PDB. All clustered and superposed models can be viewed in Mol* on the PDBe Knowledge Base website, or accessed in as raw annotations via our GraphAPI and FTP server. The clustering package is made available as an open-source Python3 package under the Apache-2.0 license.

bioinformatics↗