HYDRA

The role of hydrogen bonding and water dynamics in the self-assembly of proteins and lipids: a comprehensive experimental and computational investigation

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 Obiettivo del progetto (Objective)

'The plan proposed for the two-year Marie-Curie fellowship aims at providing the applicant with the hands on experience and theoretical knowledge required to undertake an independent simulation activity in soft condensed matter physics. This is intended to complement the experimental activity on the same subject already carried out by the applicant Dr. Antonio Benedetto.

Experimental and computational work will continue in parallel after the completion of the fellowship, providing a privileged basis for acquiring a leadership role in bio-physics soft-matter research.

Training in computational methods will take place at Queen's University of Belfast, supervised by Prof. Pietro Ballone. The acquisition of modelling and simulation experience will be driven by the development of three different but related sub-projects, concerning: (i) the role of water in the equilibrium polymerisation of actin and tubulin; (ii) the interaction of room-temperature ionic liquids with lipid bilayers; (iii) the role of hydrogen bonding and hydrophobicity in the stabilisation of amyloid fibrils, with insulin as a prototype system.

In all these problems, hydrogen bonding, hydrophobicity/hidrophilicity, and the dynamics of water molecules play the central role. Neutron scattering and simulation both represent powerful tools to investigate these properties, and their combination will provide a direct and microscopic view of the systems under investigation.

Besides providing a comprehensive training in atomistic simulation to Dr. A. Benedetto, the three subprojects are expected to provide a wealth of important new results, with important implications for pharmacology, toxicology, environmental sciences, nanotechnology and medicine.

The training and scientific work will be complemented by a series of outreach activities that are discussed in the application.'

Descrizione progetto (Article)

Water plays a vital role in many biological processes largely due to its polarity (relative separation of charge creating a local dipole moment) and its ability to form hydrogen bonds. The former makes it an excellent solvent of electrolytes (ionisable substances such as salts, acids and bases) necessary to cellular function. The latter provides a flexible and directional force that can guide the self-assembly of complex structures.

Given the ubiquitous role of water in biological processes, the EU-funded project HYDRA investigated equilibrium properties and fast dynamics of hydrogen bonding at water-biomolecule interfaces. The role of water in self-assembly of proteins and lipids was studied through a combination of neutron scattering experiments and computer simulation. The team also investigated the effects of room-temperature ionic liquids (RTILs), salts that are liquid at room temperature.

HYDRA attracted widespread attention and support from the scientific community, resulting in award of a tremendous amount of neutron beam time at numerous facilities and on powerful computational resources in Europe and the United States. The research effort enabled investigation of the same systems and problems from both an experimental and a computational point of view and produced important new insights.

Biological cell membranes are self-assembled phospholipid bilayers. Investigations into phospholipid bilayers in RTILs have provided a wealth of information about water and lipids hydrated by RTILs, in fact the most detailed information available on these systems. They will support future work for applications of RTILs in electrochemistry, pharmacology and nanotechnology.

Experiments have also addressed the kinetics of fibril formation (fibrillation) of peptides and proteins in water and in aqueous solutions of RTILs with possible pharmaceutical applications. The aggregation of proteins to form amyloid fibres is a process critically tied to the development of neurodegenerative conditions such as Alzheimer's and Parkinson's diseases. Studies of interactions between DNA and RTILs could form the basis for long-term preservation of nucleic acid samples at room temperature.

HYDRA has made a major scientific contribution that has broad-sweeping implications for the EU health care system, the EU economy and eventually EU citizens via pharmaceuticals, diagnostics and therapies with a basis in RTILs.