Biomolecular Interactions

  • molecular simulations for protein-protein interactions

Biomolecules never function in isolation. Instead, they are linked in networks of physical interactions and functional relationships. Protein complexes are essential components of cell cycle control, signal transduction, and intermediary metabolism among other biological functions.

Morphological features with advanced functionality generally drive evolution toward larger sizes. However, poor error control, coding inefficiencies and inability to regulate self-assembly impose evolutionary pressure on very large proteins. Hence, protein complexes have a clear selective advantage, combining modularity and functionality. The key phenomena in protein complexation are the initial intermolecular recognition and the subsequent interaction through highly specific contact surfaces. Detailed knowledge of the mechanism of protein-protein interaction confers the ability to regulate cellular functions by designing molecular (ant)agonists.

The integration of bioinformatics tools and molecular mechanics simulations is proposed for predicting contact maps and elucidating the energetics of protein-protein interactions. Single and coherent docking modes are being determined for protein pairs and the mechanism of protein complexation are elucidated. An automated computer-based approach for identifying connectivities and complex relationships between proteins in cellular networks is also developed.