Biological cells exhibit extensive spatial and temporal regulations, as well as many interacting partners that affect cellular pathways. The latter are characterized by reactions, environmental changes, intermolecular interactions, and allosteric modifications. All of these processes involve molecular recognition, i.e. the exquisite process by which two or more molecules interact to form a specific complex. The process is surely dominated by short- range, often-transient interactions at the contact surface of the molecules. Even conformational changes and assemblies of very large macromolecular aggregates, which can be propagated through long distances (tens of angstroms), are the effect of local interactions between small molecules (acting like messengers) or macromolecules with their cell works.

Therefore understanding how a cell works in normal and pathological conditions caused by diseases requires the integration of biological complexes into cellular pathways (the so-called systems biology). Non-molecular modeling needs to be paralleled by a quantitative molecular description of pathways, so far mostly lacking. This will impact strongly on pharmaceutical sciences, as drug target (and mutations effect) pathways, rather than a single biomolecule.

Computational-driven hypothesis will be tested against experiments performed by experimental laboratories (labs). The experimental labs will validate of the computational work, in a unique effort to dissect the molecular determinants of pathways involved in healthy as well as diseased cells.

Some of the key questions that we will address are the following: what is the effect of mutations, enzymatic inhibition and gene- knockout experiments on the cellular pathways? What is the effect of mutations on phenotypes of different nature (molecular, metabolic, morphological)? What is the effect of change in environment (e.g. oxidative stress, presence of metal ions, pH etc.) or of the addition of drugs? Can coarse-grained methodologies aimed at describing the entire pathways at the molecular scale be identified? What is the contribution of the non-coding portion of the genome to the physiology of an organism?

We believe that approaching this type of questions is one of the great challenges of Molecular Biology and that it requires an eminently interdisciplinary approach and a better combination of molecular and computational approaches.