Bcl::Cluster: A method for clustering biological molecules coupled with visualization in the Pymol Molecular Graphics System

Abstract

Clustering algorithms are used as data analysis tools in a wide variety of applications in Biology. Clustering has become especially important in protein structure prediction and virtual high throughput screening methods. In protein structure prediction, clustering is used to structure the conformational space of thousands of protein models. In virtual high throughput screening, databases with millions of drug-like molecules are organized by structural similarity, e.g. common scaffolds. The tree-like dendrogram structure obtained from hierarchical clustering can provide a qualitative overview of the results, which is important for focusing detailed analysis. However, in practice it is difficult to relate specific components of the dendrogram directly back to the objects of which it is comprised and to display all desired information within the two dimensions of the dendrogram. The current work presents a hierarchical agglomerative clustering method termed bcl::Cluster. bcl::Cluster utilizes the Pymol Molecular Graphics System to graphically depict dendrograms in three dimensions. This allows simultaneous display of relevant biological molecules as well as additional information about the clusters and the members comprising them.

Takinib, a Selective TAK1 Inhibitor, Broadens the Therapeutic Efficacy of TNF-α Inhibition for Cancer and Autoimmune Disease

“…Refinement, manual modeling and visualization were done using Coot (Emsley & Cowtan, 2004), Phenix (Adams et al, 2010) and Refmac (Murshudov et al, 2011). Ligand interaction figures were generated by PyMol (The PyMOL Molecular Graphics System (Alexander, Woetzel, & Meiler, 2011) and Ligplot+ . Data collection and final refinement statistics are given in Table S2.…”

Probing the Metabotropic Glutamate Receptor 5 (mGlu5) Positive Allosteric Modulator (PAM) Binding Pocket: Discovery of Point Mutations That Engender a “Molecular Switch” in PAM Pharmacology

“…The energy function used during the docking procedure contains terms for van der Waals attractive and repulsive forces, hydrogen bonding, electrostatic interactions between pairs of amino acids, solvation, and a statistical term derived from the probability of observing a side-chain conformation from the PDB. For each modulator, .2000 docked complexes were generated and clustered for structural similarity using bcl::Cluster (Alexander et al, 2011). The lowest-energy binding modes from the five largest clusters for each modulator were used for further analysis.…”

A Novel Ste20-related Proline/Alanine-rich Kinase (SPAK)-independent Pathway Involving Calcium-binding Protein 39 (Cab39) and Serine Threonine Kinase with No Lysine Member 4 (WNK4) in the Activation of Na-K-Cl Cotransporters

“…After creation of the appropriate files (24), 10,000 comparative models of the PF2-like domain were generated using the Rosetta loop modeling modality (25). The top 500 scoring models were then clustered based on root mean square deviation to 2.0 Å (26), and the top 10 comparative models based on Rosetta energy and clustering were selected for peptide docking. In a second step, for each of the models, the Gly-Arg-PheGln-Val-Thr hexapeptide was manually placed into the PF2-like domain that corresponded to the CCT-binding pocket of OSR1 using PyMOL (PyMOL Molecular Graphics System, Version 1.5.0.4, Schrödinger, LLC).…”