Abstract
The interaction between macromolecules is a fundamental aspect of most biological processes. The computational techniques used to study protein-protein and protein-nucleic acid interactions have evolved in the last few years because of the development of new algorithms that allow the a priori incorporation, in the docking process, of experimentally derived information, together with the possibility of accounting for the flexibility of the interacting molecules. Here we review the results and the evolution of the techniques used to study the interaction between metallo-proteins and DNA operators, all involved in the nickel and iron metabolism of pathogenic bacteria, focusing in particular on Helicobacter pylori (Hp). In the first part of the article we discuss the methods used to calculate the structure of complexes of proteins involved in the activation of the nickel-dependent enzyme urease. In the second part of the article, we concentrate on two applications of protein-DNA docking conducted on the transcription factors HpFur (ferric uptake regulator) and HpNikR (nickel regulator). In both cases we discuss the technical expedients used to take into account the conformational variability of the multi-domain proteins involved in the calculations.
Highlights
Living organisms rely on protein-protein and on protein-nucleic acid interactions to perform their functions [1,2,3,4]
We review and discuss the evolution of the techniques used by us and by other groups to study the interactions between macromolecules in two macro-test cases: (i) the prediction of the complexes formed by the accessory proteins involved in the activation of the nickel-dependent enzyme urease; and (ii) the prediction of protein-DNA complexes involving two bacterial transcriptional factor, namely the ferric uptake regulator (Fur) and the nickel regulator NikR, involved in cellular iron and nickel metabolism
These new findings, in general agreement with the proposed region of HpUreE interacting with HpUreG in the docking calculations performed earlier on the same proteins from H. pylori [41], prompted the calculation of the SpUreEG complex driven by the nuclear magnetic resonance (NMR) experimental information
Summary
Living organisms rely on protein-protein and on protein-nucleic acid interactions to perform their functions [1,2,3,4]. 18,000 in higher plants of the Arabidopsis genus [6], to 150,000–500,000 in human cells [7,8] Despite their evident importance, the interactions between macromolecules are not fully understood at the structural level. Experimental techniques can be complemented by computational docking methods aimed to model the quaternary structure of complexes formed by two or more interacting macromolecules. In the classical (or ab initio) docking methods, the calculation itself only produces plausible candidate structures. These candidates must be ranked a posteriori using scoring functions or validation/filtering procedures that use experimental data to identify structures that are most likely to occur in nature. We review and discuss the evolution of the techniques used by us and by other groups to study the interactions between macromolecules in two macro-test cases: (i) the prediction of the complexes formed by the accessory proteins involved in the activation of the nickel-dependent enzyme urease; and (ii) the prediction of protein-DNA complexes involving two bacterial transcriptional factor, namely the ferric uptake regulator (Fur) and the nickel regulator NikR, involved in cellular iron and nickel metabolism
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