A simple tool for macromolecule interfaces analysis

Background Analysis of interfaces in macromolecular complexes is essential to unveil the mechanisms underlying molecular recognition. However, currently available interface analysis tools provide important results, such as contact maps, in noneditable formats. Additionally, many of them do not provide relevant information. Results We have developed a novel fast and comprehensive tool to analyse the interfaces between any two macromolecules (i.e., either proteins or nucleic acids). The program takes as an input the coordinates of two macromolecule chains in PDB format and calculates a number of structural parameters by using both internal routines and external programs such as Naccess (for solvent accessible surface area) or DSSP (for secondary structures). As a result, the program provides extensive information about the analysed interface, including: interacting residues and atoms; polar vs. non polar nature of the interaction; and number of polar and non-polar contacts (as a rough measure of the interaction strength). These data are provided both as simple text and in formats that can be easily parsed or ready to be imported in spreadsheet applications or PyMol for further structure analysis and visualization. We have applied the program to the analysis of two different types of interfaces: i) between tRNA molecules and the cognate aminoacyl-tRNA synthetases; and ii) between the subunits of multimeric protein assemblies. In the first case, based on the results of our analysis we designed small molecule peptides endowed with therapeutic properties against defective phenotypes arising from single-point mutations in human mt-tRNA, which could be used as lead molecules to develop therapeutic agents. In the second case, elucidation of the structural difference between subunit interfaces in the decamer and doubledecamer forms of Schistosoma mansoni peroxiredoxin I allowed us to understand the structural events causing the shift between the two assemblies and their relative functions. Conclusion We have developed a fast and interactive program to analyse interfaces involving protein and/or nucleic acid molecules whose output can be easily handled and parsed by the user. The program will be soon available to users as a web server.