Giovanni La Penna

Semiempirical and ab initio (Car-Parrinello) modelling of proteins, metallo-proteins, nucleic acids and polysaccharides

Keywords Computational chemistry, Statistical mechanics, Bioionorganic chemistry, DNA, RNA, Chromatin, Hyaluronan, Cytochrome, Hydrogenase, Prion

Expertise
Computer modelling is a tool for investigating interactions in biological systems, allowing the interpretation of many experimental data in terms of physics and chemistry. Inexpensive computer clusters are now available for extended statistical analysis of conformations (protein and RNA folding, protein-DNA interactions) and for extended electron structure calculations (interactions of metal ions with biological macromolecules).

Our recent research focused on the following topics:

• The study of protein-DNA interactions in chromatin, this latter the building block of the genetic material in eukaryotic cells.
• The collection and analysis of large statistics for proteins containing metal ions (cytochrome b5 and c).
• The ab initio molecular dynamics (Car-Parrinello scheme) of metal ions in models of protein environments (cytochrome c, the copper binding site of prion, zinc/copper interactions with amyloid peptides, hydrogenases).
• The calculation of the molecular dynamics based on diffusion theory, in order to study the local dynamics on the basis of large Monte Carlo statistical sampling of macromolecules (RNA, hyaluronan).

Applications
Modelling (including molecular simulation) is an interpretative tool. Interactions with groups involved in understanding experimental results about biological processes (in vitro and in vivo) and/or in designing processes for technological bioinspired processes is necessary to validate and apply theories, models and algorithms. The topics of our recent research are all involved in important biological processes where the FP7 EU programme invested funds. Here following are only a few issues.

• The interactions between DNA and proteins allow the compaction of a huge amount of genetic information into the room of the cell nucleus. This compaction deals with regulation of gene expression and epigenetic modifications in a complicate manner. The understanding of the mechanisms at the basis of chromatin structure is an essential step in cell biology. Interactions between RNA fragments and proteins and RNA aggregates are at the basis of RNA degradation and splicing. These latter processes are key steps in gene silencing and/or expression.
• The interactions between metal ions and proteins is at the basis of metabolic disfunctions and of related degenerative diseases (BSE, CJD, Alzheimer, Parkinson, ALS). Most of the proteins involved in these diseases are probably involved in metal ion trafficking (prion, APP, alpha-synuclein, SOD). Enzymes involved in energy storage processes (cytochromes, hydrogenases) allow chemical processes of potential industrial applications (catalysis in redox reactions, hydrogen production).
• Molecular dynamics as at the basis of the kinetics of biological processes and of transport processes involving macromolecules. The exceptional visco-elastic properties of hyaluronan in animal tissues is an example of this issue. Diffusion theory coupled with extended statistical calculations is among the most advanced tools in the field.

List of publications, updated november 20th 2008