Yashraj Kulkarni
A novel pipeline for peptide probe/drug design applied to brain receptors
Yashraj Kulkarni, Department of Drug Design and Pharmacology at University of Copenhagen, has received a Lundbeck Foundation Postdoc grant worth DKK 2,398,229.
About the project
G protein-coupled receptors (GPCRs) mediate the effects of two-thirds of human hormones and one-third of clinical drugs. However, hundreds of GPCRs lack functional probes or are targets of drug discovery. Therefore, developing methods for probe/drug design has a huge impact on human physiology and health.
A recent surge in atomic 3D structures of GPCRs and models from AlphaFold now open unprecedented opportunities to develop such probe/drug methods with unique advantages across numerous drug targets.
The project will firstly develop a peptide pipeline applicable to peptide, protein, or ’orphan’ receptors, and secondly identify receptor ligands modulating the brain from the bloodstream or via the gut-brain axis.
Building a unique pipeline able to transfer peptide ligands from an old receptor target and re-optimize them for potent and selective activation of a new target GPCR.
As data, the pipeline will use all atomic 3D structures of all 699 human peptide-GPCR complexes from experiments or modelled using AlphaFold. Yashraj Kulkarni will design optimized ligands using computational drug design tools and molecular dynamics simulations. All ligands designed on the computer will be synthesized and tested for pharmacological effects.
The probe/drug design pipeline has the potential to catalyze the development of more and better drugs and probes for functional investigation of uncharted signaling systems towards tomorrow’s drug targets.
