MolTalk – a programming library for protein structures and structure analysis

BMC Bioinformatics Software MolTalk - a programming library for protein structures and structure analysis Alexander V Diemand*1 and Holger Scheib2 0 University of Geneva and Swiss Institute of Bioinformatics, Centre Medicale Universitaire , 1, rue Michel-Servet, 1211 Geneva 4 , Switzerland 1 University of Lausanne and Swiss Institute of Bioinformatics , 155, chemin de Boveresses, 1066 Epalinges s/Lausanne , Switzerland Background: Two of the mostly unsolved but increasingly urgent problems for modern biologists are a) to quickly and easily analyse protein structures and b) to comprehensively mine the wealth of information, which is distributed along with the 3D co-ordinates by the Protein Data Bank (PDB). Tools which address this issue need to be highly flexible and powerful but at the same time must be freely available and easy to learn. Results: We present MolTalk, an elaborate programming language, which consists of the programming library libmoltalk implemented in Objective-C and the Smalltalk-based interpreter MolTalk. MolTalk combines the advantages of an easy to learn and programmable procedural scripting with the flexibility and power of a full programming language. An overview of currently available applications of MolTalk is given and with PDBChainSaw one such application is described in more detail. PDBChainSaw is a MolTalk-based parser and information extraction utility of PDB files. Weekly updates of the PDB are synchronised with PDBChainSaw and are available for free download from the MolTalk project page http://www.moltalk.org following the link to PDBChainSaw. For each chain in a protein structure, PDBChainSaw extracts the sequence from its coordinates and provides additional information from the PDB-file header section, such as scientific organism, compound name, and EC code. Conclusion: MolTalk provides a rich set of methods to analyse and even modify experimentally determined or modelled protein structures. These methods vary in complexity and are thus suitable for beginners and advanced programmers alike. We envision MolTalk to be most valuable in the following applications: 1) To analyse protein structures repetitively in large-scale, i.e. to benchmark protein structure prediction methods or to evaluate structural models. The quality of the resulting 3D-models can be assessed by e.g. calculating a Ramachandran-Sasisekharan plot. 2) To quickly retrieve information for (a limited number of) macro-molecular structures, i.e. H-bonds, salt bridges, contacts between amino acids and ligands or at the interface between two chains. 3) To programme more complex structural bioinformatics software and to implement demanding algorithms through its portability to Objective-C, e.g. iMolTalk. 4) To be used as a front end to databases, e.g. PDBChainSaw. - Background The major demand from Life Sciences towards bioinformatics today is to combine the often heterogeneous information available and make it easily accessible to a broad range of users. In the past, these efforts concentrated on coping with the overwhelming amount of data that entered and still enter nucleotide and protein sequence databases [1,2]. Today, other information sources, such as protein structures, subsequently come under the spotlight of a broader scientific community. In contrast to the sequence world, only one central data resource exists for protein structures, the Protein Data Bank (PDB) [3]. Despite the undisputed advantage of having all structural data available from one source in a common file format, protein structures impose a new level of complexity. They carry information about where in space the adjacent residues of a protein sequence are located. Furthermore, protein structures provide insights into the spatial environment of an amino acid, which is different from its sequence neighbourhood, as well as into its interactions with other residues or heterogeneous ligands. This wealth of information contains answers to questions as diverse as to how proteins function or what compounds may interact with a given protein. However, these answers often remain inaccessible to a broader scientific community. To overcome this information gap, we developed MolTalk. MolTalk consists of a programming library implemented in Objective-C [4] that maps PDB structure files to object space as well as of a scripting language based on Smalltalk [5]. Moreover, MolTalk provides numerous methods that enable both the novice as well as the expert structural bioinformatician to rapidly develop software tailored towards their individual needs and to allow for novel insights from protein structure analyses. As an application for MolTalk we describe PDBChainSaw, a mirroring and data extraction routine for PDB files. Implementation MolTalk is composed of two functional parts: (1) the programming library libmoltalk and (2) MolTalk, the Smalltalk interpreter. The libmoltalk library implements classes (Figure 1) in Objective-C [4] whereas the interpreter MolTalk is based on StepTalk [5], a Smalltalk interpreter for GNUstep [6]. The interpreter interacts with all classes defined in libmoltalk and is used as a front end to this library. The classes implemented in libmoltalk are summarised in groups, namely "structural", "mathematics", and "others". Their complexity and flexibility vary as indicated by the labels "Basic" and "Xtra" (Table 1). "Basic" classes can be used by even novice users without special training, whereas classes labelled "Xtra" indicate a higher level of potential difficulty for a user, but allow often, at the same time, a higher degree of flexibility in software development (for details, please refer to the manual pages at http:/ /www.moltalk.org/Manual.html. Each class consists of a set of methods, which again are labelled either "Basic" or "Xtra". Independent of their class, methods can be organised into (1) "basic features", (2) "extended features", (3) "mathematical functions", and (4) "others". "Basic features" enable mapping into object space and querying. "Extended features" can be further sub-divided into "operations" and "manipulations". "Operations" include e.g. superimposition, structural alignment, and transformation, respectively. With "manipulations" chains, residues or atoms can be added to or removed from a structure. "Mathematical functions" allow the calculation of vectors and matrices to perform spatial transformations. The features summarised in "others" regulate input and output. In Table 1, a list of the potentially most important methods and classes of the group "Structure" is provided. Results and Discussion PDBChainSaw Extracting and deriving knowledge from PDB files remains a non-standard procedure to date. Therefore, we developed MolTalk to provide and facilitate access to this valuable information. As an example for a possible use of MolTalk, we present PDBChainSaw, a relational database of protein structure chains, which is used in the ModSNP project to model (...truncated)