Section: Application Domains

Structural Biology

Structural biology is a branch of molecular biology, biochemistry, and biophysics concerned with the molecular structure of biological macromolecules, especially proteins and nucleic acids. Structural biology studies how these macromolecules acquire the structures they have, and how alterations in their structures affect their function. The methods that structural biologists use to determine the structure typically involve measurements on vast numbers of identical molecules at the same time, such as X-Ray crystallography, NMR, cryo-electron microscopy, etc. In many cases these methods do not directly provide the structural answer, therefore new combinations of methods and modeling techniques are often required to advance further.

We develop a set of tools that help biologists to model structural features and motifs not resolved experimentally and to understand the function of different structural fragments.

• Symmetry is a frequent structural trait in molecular systems. For example, most of the water-soluble and membrane proteins found in living cells are composed of symmetrical subunits, and nearly all structural proteins form long oligomeric chains of identical subunits. Only a limited number of symmetry groups is allowed in crystallography, and thus, in many cases the native macromolecular conformation is not present on high-resolution X-ray structures. Therefore, to understand the realistic macromolecular packing, modeling techniques are required.

• Many biological experiments are rather costly and time-demanding. For instance, the complexity of mutagenesis experiments grows exponentially with the number of mutations tried simultaneously. In other experiments, many candidates are tried to obtain a desired function. For example, about 250,000 candidates were tested for the recently discovered antibiotic Platensimycin. Therefore, there is a vast need in advance modeling techniques that can predict interactions and foresee the function of new structures.

• Structure of many macromolecules is still unknown. For other complexes, it is known only partially. Thus, software tools and new algorithms are needed by biologists to model missing structural fragments or predict the structure of those molecule, where there is no experimental structural information available.