Computational Design of Tailored Kappa Opioid Receptor (KOR) Modulators
Prof. Dr. Gerhard Wolber
The Kappa Opioid Receptor (KOR) plays a pivotal role in regulating pain, mood, and addiction pathways, making it a key target for drug development aimed at treating chronic pain, mood disorders, and addiction. The goal of this PhD project is to build on recent research (http://dx.doi.org/10.3390/molecules28020718 and http://dx.doi.org/10.1021/acs.jmedchem.4c00590) by developing tailored KOR modulators through a computational approach, with a focus on optimizing their functional selectivity (signaling bias).
The project will leverage structure-based drug design (SBDD), and may incorporate machine learning techniques to develop novel KOR modulators, drawing inspiration from the binding mode of Salvinorin A. Newly identified modulators will undergo in vitro testing to assess their biological activity and receptor selectivity. Feedback from these experimental results will then refine the computational models, driving further optimization of lead compounds. Additionally, molecular dynamics simulations will be employed to evaluate the interaction profiles between KOR and its ligands, while also examining the impact of different binding modes on downstream signaling pathways.
Requirements:
- Master’s degree in Pharmacy, Biochemistry, Chemistry, or a related field with excellent grades
- Interest and expertise in molecular modeling, in particular structure-based design
- Experience and/or interest programming (Python, RDKit), and virtual screening techniques
What we offer:
- Interdisciplinary Research Environment: You will collaborate closely with experts in computational drug design, and experimental research, gaining experience in a collaborative and dynamic research setting.
- Cutting-Edge Research Infrastructure: Access to state-of-the-art computational resources for molecular modeling, virtual screening, and machine learning.
- Opportunities for Career Development: Participation in conferences, workshops, and exposure to international collaborations to further develop your expertise and career in the field.
More info on the research group
© Gerhard Wolber