Reading PDB: Perception of Molecules from 3D Atomic Coordinates

Abstract

The analysis of small molecule crystal structures is a common way to gather valuable information for drug development. The necessary structural data is usually provided in specific file formats containing only element identities and three-dimensional atomic coordinates as reliable chemical information. Consequently, the automated perception of molecular structures from atomic coordinates has become a standard task in cheminformatics. The molecules generated by such methods must be both chemically valid and reasonable to provide a reliable basis for subsequent calculations. This can be a difficult task since the provided coordinates may deviate from ideal molecular geometries due to experimental uncertainties or low resolution. Additionally, the quality of the input data often differs significantly thus making it difficult to distinguish between actual structural features and mere geometric distortions. We present a method for the generation of molecular structures from atomic coordinates based on the recently published NAOMI model. By making use of this consistent chemical description, our method is able to generate reliable results even with input data of low quality. Molecules from 363 Protein Data Bank (PDB) entries could be perceived with a success rate of 98%, a result which could not be achieved with previously described methods. The robustness of our approach has been assessed by processing all small molecules from the PDB and comparing them to reference structures. The complete data set can be processed in less than 3 min, thus showing that our approach is suitable for large scale applications.

Protoss: a holistic approach to predict tautomers and protonation states in protein-ligand complexes

“…This evidently also applies to non-standard residues for which no predefined template is available. We use a method based on the NAOMI model for that purpose [19]. Both strategies eventually result in isolated components which have to be connected in order to build the complete protein structure.…”

Automatic molecular structure perception for the universal force field

“…A substantial amount of work has been proposed for perception of molecular systems. [18][19][20][21][22][23][24][25][26][27][28] Since the relative positions of the atoms in a given system are strongly related to atoms properties, state-of-the art methods propose different approaches to perform a reverse engineering process that allows to retrieve these properties from the known atom coordinates. Although the strategies used by these methods may differ largely, the same key descriptive features are usually being assessed: molecular connectivity, the order of the associated bonds, local atom geometries (e.g., linear, trigonal, tetrahedral, octahedral) and atom hybridizations (e.g., sp, sp 2 , sp 3 ), oxidation numbers, etc.…”

“…The values of covalent radii that we use are those published by the Cambridge Crystallographic Data Center. [30] The tolerance distance th may slightly differ according to the source, varying from 0:4Å [22,24,26,27] to 0:45Å, [19,20] although more complex options can be used, as in Ref. [25], where th also depends on the pair of elements involved.…”

“…The problem of assigning bond orders has been addressed by various types of approaches and may exploit very different information about a molecular system, such as its connectivity, [24,39] local geometries, [26,27] hybridization states, [19] ionization and charges, [22] atom types [23] or small fragment analysis. [25] We refer the reader to A. Dehof [40] for a detailed description of the state of the art.…”

MONA – Interactive manipulation of molecule collections

“…If an entry consists of multiple disconnected components, currently solely the largest component is kept. Furthermore, it is possible to import small molecules from PDB files using the method described in [8]. In this case all components of the entry are imported.…”