The aim of the EMPHABIOSYS project is to understand proteins, the molecular machines of life that are key actors in virtually all biochemical processes within the cell. At a biochemical level, proteins are short chain molecules built from a menu of 20 amino acids, each bearing a distinct side-chain, linked together into a linear polypeptide chain. The proteins we observe in nature today have evolved to perform specific functions. They are physiologically active only when their linear chain folds in aqueous solution into a unique three-dimensional structure characteristic of each protein. The knowledge of this so-called native state structure of a protein is crucial for understanding its biological function. The way a protein can efficiently, reversibly, and reproducibly acquire its unique native state, starting from an extended, random-coil configuration, is the so-called protein folding problem. It represents a remarkable example of a self-assembly process that has so far eluded a complete explanation, notwithstanding more than 50 years of intensive research. Protein folding remains one of the fundamental open questions across the fields of contemporary molecular biology, biochemistry, and biophysics. The journal Science on its 125th anniversary in 2005, classified it among the Top100 most important and challenging problems facing scientists in the next quarter of century.The solution of the protein folding problem is of paramount theoretical and practical importance. It will have immediate impact on molecular biology, drug design and nanotechnology. Inspired by nature, the ability to understand and mimic this biological mechanism would lead to novel ways of fabricating biomaterials, engineered through a bottom-up approach. More importantly, it will contribute to the societally important issue of human health through an understanding of the principles behind protein folding (and misfolding). These are responsible for cell function and malfunction. Examples include amyloid formation implicated in human neurodegenerative diseases such as Alzheimer’s and Parkinson’s and type 2 diabetes due to the misfolding of insulin protein. Protein folding problem is very complex: 20 different amino acid types, the role of a water as a solvent; a huge number of degrees of freedom is involved. The puzzle is how proteins succeed to find their respective unique native states so quickly? Biological folding times are in the range from microseconds to seconds, whereas one might have naively expected astronomically large times if the search had been random among the enormously large number of possible conformations. Despite all this, proteins share remarkable common properties: they are made of building blocks of topologically one-dimensional alpha-helices and almost planar, effectively two-dimensional beta-sheets connected by loops and assembled into the three-dimensional native state structures. They fold rapidly and efficiently, and act as amazingly effective molecular machines. The overall objective of the project is to find from first principles, using minimum number of essential ingredients, the hidden simplicity that must underlie protein problem and explain all remarkable common properties of proteins.
