We also added polar and weak polar contact types, which correspond to hydrogen bond and weak hydrogen bond interactions without angle terms; these are less sensitive to hydrogen placement

We also added polar and weak polar contact types, which correspond to hydrogen bond and weak hydrogen bond interactions without angle terms; these are less sensitive to hydrogen placement. Overall, the SIFt typifies the interactions made between a given atom pair and can be enumerated for groups of atoms, for example , a small-molecule ligand. mutations in genetic diseases and protein engineering. Reliable and comprehensive methods to evaluate and visualise the full range of potential molecular interactions across many atom types present in protein structures are invaluable. Arpeggio calculates all intra- and interatomic interactions in macromolecular structures, including van der Waals’, ionic, carbonyl, metal, hydrophobic, and halogen bond contacts, and hydrogen bonds and specific atomaromatic ring A 83-01 (cation, donor, halogen, and carbon) and aromatic ringaromatic ring () interactions, within a provided Protein Data Bank file. Calculations can be within or between any combination of protein, DNA, or small organic molecules. The Arpeggio web server (http://bleoberis.bioc.cam.ac.uk/arpeggioweb/) was implemented to provide a freely available, user-friendly web interface for the exploration of molecular interactions within protein structures, including through WebGL-based visualisation of interactions and downloadable interactive PyMOL session files. Arpeggio is written in Python, requires only Open Source dependencies, and is freely available for download athttps://bitbucket.org/harryjubb/arpeggiofor use in custom analyses. == Introduction == Molecular recognition is driven in part by the favourable matching of chemistry between two or more molecules. Many known interactions in molecular recognition can be represented by pairwise contacts between atoms[1],[2],[3],[4],[5],[6],[7],[8]. While interatomic, non-bonded interactions, such as hydrogen bonding and -stacking interactions, are generally intuitively recognised by the trained observer, it is helpful to visualise them based on defined criteria. Definition and enumeration/visualisation of interactions as opposed to intuition help to ensure that we have Ctsk a more rigorous, impartial, and complete understanding of the nature of molecular binding sites. This allows the A 83-01 systematic evaluation of the interactions made in, for example , proteinligand interactions, thus ensuring that key interactions are not overlooked[9]. Some tools are available that aid in this understanding, such as A 83-01 the Ligand Protein Contacts server[10]and GIANT[9], and specific programs for calculating individual interaction types such as polar contacts in PyMOL and hydrogen bonds A 83-01 with Joy[11], REDUCE[12], HBPLUS[5], Bioptools[13], and LIGPLOT +[14]. However , these tools use a limited set of interaction types and are confined to proteinligand interactions for visualisation. FingerPrintLib[15]and PyPLIF[16]calculate multiple interaction types but are restricted to protein interactions with small organic molecule ligands only. PLIP[17]recently expanded these interactions to look at all proteinligand interactions, but like earlier methods is limited to binary interaction fingerprints in its output. We have previously published databases of calculated interatomic interactions covering the Protein Data Bank (PDB[18])[19],[20],[21],[22],[23]. We now present Arpeggio, a web server for calculating interatomic interactions of 15 subtypes based on atom type, distance and angle terms. Arpeggio can be applied not only to proteinligand interactions but also to proteinprotein, proteinnucleic acid, and nucleic acidnucleic acid interactions. The server can accept user-submitted structures in addition to PDB accession codes and thus can be used to calculate interactions for non-PDB structures such as homology models or docking poses. The web server provides downloadable tabular data enumerating interactions between molecular entities of interest for further analysis, in addition to WebGL- and PyMOL session-based visualisation of all interactions present in an input structure. The Arpeggio Python program that calculates interactions is Open Source (available athttps://bitbucket.org/harryjubb/arpeggio), has only Open Source dependencies, and can be installed and run on Linux and Mac OSX. == Results == == Arpeggio program implementation == Arpeggio is implemented in Python and uses BioPython[24]and OpenBabel[25]to process PDB structure files. OpenBabel is used to assign atom types to each atom in the structure via SMARTS (a molecular pattern-matching language) queries, and BioPython’s KDTree implementation is used to extract nearest-neighbour atoms within a 5- radial cutoff. Each pairwise interatomic contact is given a structural interaction fingerprint (SIFt)[26]using an expanded definition of the[15]interaction.