Co-Design Project 6

Co-Design Project 6 -
Modelling Drug Discovery

Any innovative approaches to brain diseases require a detailed understanding of the causes of the diseases at all levels of organisation from the molecular to the cognitive & system levels, as well as disease progression and response to treatment. 

These issues are particularly challenging for neurological and psychiatric diseases due to the extreme complexity of the nervous system. At this stage, no efficient curative treatments yet exist for neurodegenerative diseases such as Alzheimer's and Parkinson's, despite large research investments.

The search for new drugs for brain diseases is considered an ethical priority for neuroscience research, and the HBP is in a unique position to contribute to it. In particular, this will be through  better definitions and diagnoses of the diseases with the generation and organisation of large sets of data, and mostly through the ability to simulate the responses in the brain to various influences, ranging from drug administration, environmental care, to gene mutations. The aim of CDP6 is, ultimately, to coordinate research efforts to establish new protocols to increase the efficiency and speed of the drug discovery process, thereby enhancing innovation at lower costs. Several areas of research have been identified that are of particular interest for the drug design programmes, They include ligand-gated and G-protein linked receptors and their allosteric properties, diversity of receptor distribution in the brain, glial cell metabolism, and physiological and drug-elicited synaptic plasticity. Functional models of signalling and metabolic pathways, from which drug discovery targets may be elucidated, may be provided through data integration and analysis and simulations at the atomic, molecular and cellular levels.

This obviously requires a significant research investment. CDP6 therefore intends to build on the HBP Research Infrastructure for data collection and analysis, and to complement HBP funding to seek external funding from national and private agencies, in particular pharmaceutical companies. Importantly, all of the proposed simulations will be performed on the High Performance Analytics and Computing Platform (HPAC) from HBP, and will therefore benefit from close collaboration with Subproject 7. CDP6 will demonstrate the key role of HPAC-based simulations in the design of new classes of drugs targeting the multiplicity of allosteric sites carried by the receptor proteins in the course of their conformational transitions.

The CDP6 Products to be developed are as follows:

  • CDP6-P1: Modelling receptor allostery
  • CDP6-P2: Pharmacological modulation of synaptic plasticity and drug design
  • CDP6-P4: Ethical implications of drug design

CDP Science Leader: Jean-Pierre CHANGEUX

CDP Implementation Leader: Paolo CARLONI