Par défaut le dernier rapport d’activité le RAweb :
Overall objectives
Computational Challenges in Structural Biology
NB: This section has been remodeled since the death of Dave Ritchie in 2019.
Many of the processes within living organisms can be studied and understood in terms of biochemical interactions between large macromolecules such as DNA, RNA, and proteins. To a first approximation, DNA may be considered to encode the blueprint for life, whereas proteins and RNA make up the three-dimensional (3D) molecular machinery. Many biological processes are governed by complex systems of proteins and/or RNA which interact cooperatively to regulate the chemical composition within a cell or to carry out a wide range of biochemical processes such as photosynthesis, metabolism, and cell signalling, for example. It is becoming increasingly feasible to isolate and characterise some of the individual molecular components of such systems, but it still remains extremely difficult to achieve detailed models of how these complex systems actually work. Consequently, a new multidisciplinary approach called integrative structural biology has emerged which aims to bring together experimental data from a wide range of sources and resolution scales in order to meet this challenge 58, 72.
Understanding how biological systems work at the level of 3D molecular structures presents fascinating challenges for biologists and computer scientists alike. Despite being made from a small set of simple chemical building blocks, protein and nucleic acid (NA) molecules have a remarkable ability to self-assemble into complex molecular machines which carry out very specific biological processes. As such, these molecular machines may be considered as complex systems because their properties are much greater than the sum of the properties of their component parts.
Two Research Axes
The overall objective of the CAPSID team is to develop algorithms and software to help study biological systems and phenomena from a structural point of view. In particular, the team aims to develop algorithms which can help to model the structures of large multi-component biomolecular machines and to develop tools and techniques to represent and mine knowledge of the 3D shapes of proteins, NA and their interactions. Thus, a unifying theme of the team is to tackle the recurring problem of representing and reasoning about large 3D macromolecular shapes. More specifically, our aim is to develop computational techniques to represent, analyse, and compare the shapes and interactions of biomolecules in order to better understand how their 3D structures relate to their biological function. In summary, the CAPSID team is organised according to two research axes whose complementarity constitutes an original contribution to the field of structural bioinformatics:
- Axis 1: Knowledge Discovery in Structural Databases,
- Axis 2: Integrative Multi-Component Assembly and Modeling.
In the first axis, our main objective is to design, implement and test new KDD (“Knowledge Discovery in Databases”) approaches to exploit specifically the structural information contained and sometimes hidden in many biological databases. These approaches will be oriented towards understanding molecular interactions in living organisms under physiological or pathological conditions.
In the second axis, our main objective is to propose new and fast methods to model the 3D structure of multi-component systems and characterize their dynamic behaviour. The challenge here is to integrate molecular flexibility into 3D models, thanks to molecular dynamics simulation and/or combinatorial approaches.
Finally, the complementarity of the two axes will be expressed through a common objective oriented towards the proposal of possible new treatments against diseases, based on the knowledge extracted and on the advances in 3D modeling of flexible molecular interactions. This objective will benefit from our network of biologist and clinician partners.
