Structural bioinformatics of proteins combined with computational protein biophysics: Implications for nanotechnology exemplified by G protein-coupled receptors

Abstract

It has long become evident that bioinformatics of genes and proteins, and biophysical understanding of the mechanisms underlying biomolecular function are very incomplete without one another. Thus, our previous studies have shown that significant insights could be gained in interpreting DNA microarray data within non-statistical, physical criteria-based approaches. More, the “leader gene” approach based on analysis of protein and gene interactions, developed in Prof. Nicolini’s team, allowed to identifying key genes involved in the given biological process, adding further insights into microarray data. On the other hand, our biophysical studies on the role of electrostatics in protein functioning showed that bioinformatics extension of the results, via homologous proteins, was strongly beneficial for understanding protein functioning, especially for its nanotechnological optimization. This report focuses on G Protein-Coupled Receptors (GPCR), especially the most common drug targets like adrenoreceptors and also light-sensitive proteins with enormous nanotechnology potential like octopus rhodopsin. For such proteins, the key property is their dynamics, especially the parts of the protein conformational space available to them, and how that available space is affected by drug binding or a quantum of light. We describe the combined use of molecular dynamics and structural bioinformatics analysis in exploration of the GPCR conformational space, and show insights into their function and its further optimization. Such insights are unavailable without the combination of biophysics and bioinformatics that could be properly termed “physical bioinformatics”.