Understanding Protein Structure-Function: A Complex Network View

Proteins, “work-horses” in the living cells performing diverse functions, are synthesized inside the cell as a linear chain of small molecules (amino acids), which then fold into three-dimensional structures that confers them the ability to perform specific functions. The structure-function paradigm in proteins implies that the unique three-dimensional structure of a protein is determined by its primary sequence of amino acids, and the structure regulates the function of a protein. In this presentation, I will first show (resonating with what was considered at SFI more than 25 years ago) that these “non-living” (non self-replicating) molecules are complex adaptive systems. I will then demonstrate how the three-dimensional structure of a protein (as available in the structural biology databases) can be described using the complex network approach. Finally I will elucidate cases, using network and molecular dynamics approaches, where proteins and their mutants, having no significant overall variation in their three-dimensional structures, exhibit large functional changes.