Proteins and supercomputers: using computation to unravel the rules that govern life

Molecular dynamics is a biocomputational tool that allows the scientists to describe the movements of all the atoms of a protein over time
Molecular dynamics is a biocomputational tool that allows the scientists to describe the movements of all the atoms of a protein over time

Biocomputation, with supercomputers as key tools, is allowing scientists to respond to many unanswered questions about these crucial agents for life.

The machinery of life depends on proteins. These molecules perform vital roles in the organism: they contribute to maintaining cell structure; they are responsible for mechanical cellular tasks; they are decisive for internal and external communication by the cell; they regulate gene expression; they are key elements of the immune system; and they catalyze the reactions that take place in the organism. Proteins are organic molecules comprising tens, hundreds and even thousands of amino acids organized into long chains, which fold on themselves to form specific structures. For decades, scientists have known that in general the sequence of amino acids that comprises a protein determines its structure and function. However, exactly how the sequence translates into a physical structure remains unknown.

Understanding the mechanisms by which proteins are made, how and why they fold in a specific manner, how they act and interact, and finally improving our knowledge of how proteins work are the most exciting challenges faced in biomedical research. Indeed, biocomputation, with supercomputers as key tools, is allowing scientists to respond to many unanswered questions about these crucial agents for life.

Protein flexibility and molecular dynamics techniques

In recent years, scientists have discovered that the function of a protein is determined both by the stability of its structure and by conformational changes in response to external stimuli. This is what is known as the molecular flexibility of the protein. Thus, data on how and why proteins change their conformation and react to alterations in their milieu is crucial to improve our understanding about how biomolecules work.

Describing this flexibility experimentally is a complex task that requires computer modelling techniques. Modelling allows bioinformaticists to track the movements of all atoms in a protein over time. Molecular dynamics (MD) is the most efficient simulation technique available and one of the areas of study that uses the highest degree of the world’s supercomputing resources.

The team headed by Modesto Orozco, researcher at IRB Barcelona, Principal Investigator of the Bioinformatics and Molecular Modelling Group, and Director of the Computational Biology Programme at the Barcelona Supercomputing Center, is developing an extensive “library” of 1,900 proteins in motion with the aid of the MareNostrum supercomputer. The database, called MoDel, will allow users to observe how 3D structures of representative proteins move in their environments. The MareNostrum supercomputer, the most powerful in Europe and fifth most powerful in the world, is a key instrument to perform what is to date one of the largest projects in the world devoted to protein dynamics.

A boost for drug design

Information about protein structure and dynamics is crucial for the structure-based molecular design of drugs that have the capacity to interact with a target protein to cancel its biological function.

Researchers believe that in the next five years the capacity of supercomputers and calculation programmes will have evolved to an extent to provide true-scale information about protein folding and unfolding and ligand-protein dynamics and interrelation (interactions?). These breakthroughs will help scientists to decipher the molecular bases of diseases associated with abnormal protein folding, such as in neurodegenerative diseases like Alzheimer’s, Mad Cow Disease, and some types of cancer.

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