Computational biophysics and structural bioinformatics of GPCR signaling
Dr. Abrol's research lab is focused on developing and using computational methods to probe how protein structure and biochemical interactions of G protein-coupled receptors (GPCRs) determine cellular signaling and physiology, as well as how this knowledge can be used for the rational design of drugs targeting GPCR signaling pathways.
GPCRs are integral membrane proteins that form the largest superfamily in the human genome. The activation of these receptors regulates key physiological processes (e.g., neurotransmission, cellular metabolism, immunity, differentiation), through a balance of G protein-coupled and beta-arrestin-coupled signaling pathways. This has made them targets for ~50% of drugs in the clinic.
Research in the Abrol Lab lies at the interface of Chemistry and Biology, using computational biophysics and structural bioinformatics to gain mechanistic insights into GPCR signaling. The research follows four major themes to connect the sequence, structure, and signaling of GPCRs:
Connecting sequence, structure, and signaling of GPCRs
How do GPCRs behave as allosteric machines and exhibit biased signaling?
Developing next-generation computational methods to map the conformational space of GPCRs and predict their effects on intracellular signaling pathways.
How do GPCRs fold in the membrane?
Investigating the thermodynamics of GPCR insertion and folding in lipid bilayers to understand disease-associated mutations and develop therapeutic interventions using pharmacological chaperones.
How do GPCR sequence variations lead to observed signaling and disease?
Building structural bioinformatics tools that combine evolutionary analysis with structural data to understand the role of specific residues in GPCR functional divergence.
How to rationally design treatments targeting specific pathways?
Applying structure-based approaches to discover therapeutics for diabetes, melanoma, breast cancer, and neurodegenerative diseases (Parkinson's, Alzheimer's, multiple sclerosis) with high efficacy and reduced side-effects.
Active research initiatives
Investigating advanced techniques for [specific challenge]. This project aims to develop a comprehensive framework that can be applied across multiple domains.
Developing innovative solutions for [real-world application]. Our interdisciplinary team is working to create practical tools that can make a tangible impact.
Exploring the potential of [emerging technology] in addressing [specific problem]. This cutting-edge research pushes the boundaries of current knowledge.
Partnering with leading institutions worldwide
CSUN
Medical Center
Japan
Massachusetts
Canada
NIH
NIH
Grateful for the support of our funding partners
