Scientists at the University of North Carolina School of Medicine have made a breakthrough in understanding how cells respond to some of the most widely used medicines at the molecular level. Their study, published in the journal Proceedings of the National Academy of Sciences (PNAS), demonstrates a very powerful computational method on how important proteins transmit cellular signals inside our bodies. Researchers hope these new findings could help create safer and more effective treatments for a wide range of conditions ranging from heart disease to mental health disorders.
Many drugs work by targeting proteins called G protein-coupled receptors (GPCRs), which help cells respond to signals like hormones and neurotransmitters. These receptors are the focus of about one-third of all prescription drugs. Until now, scientists didn't fully understand how the "G proteins" break away from drug-activated receptors on the cell surface to continue the signaling process.
Through advanced computer simulations using an "accelerated molecular dynamics" method, UNC researchers enabled identification of G dissociation pathways and watched how these proteins broke away to carry signals deeper inside the cell. Their simulations matched real lab results and showed how a new type of drug compounds can slow down this breakaway process. This discovery shows a clearer picture of how medicines take effect inside our cells.
Yinglong Miao, PhD
"Through international collaboration with a team at Monash University in Australia, we found these compounds could slow down the G protein dissociation in consistent simulations and experiments," said Yinglong Miao, PhD, corresponding author, associate professor in the Department of Pharmacology and Computational Medicine. "The small molecules we studied were a special class of drug leads that can bind target GPCRs with high selectivity. Such compounds can avoid toxic side effects in patients. They are also candidates for treating neuropathic pain without causing drug addiction."
This insight could help drug developers to design more precise medicines that fine-tune cell signaling, potentially reducing side effects and improving treatment for a variety of health conditions.
