Design and Characterization of Potent and Selective C3aR Antagonists for Anti-inflammatory Therapy

Professor Introduction

W. H | Ph.D. in  Chemistry

Home Institute： State University of New York at Albany

Project Description

The C3a receptor (C3aR) is a G protein-coupled receptor (GPCR) that, when bound to the anaphylatoxin C3a, triggers inflammatory responses. Targeting the C3a receptor has emerged as a promising anti-inflammatory therapy. The structure of the C3a-C3aR complex, revealed by cryo-electron microscopy (Cryo-EM), paves the way for designing potent and selective C3aR antagonists. In this research project, we aim to develop novel antagonists targeting the C3a receptor using ligand design techniques. We will employ a combination of ligand docking and molecular dynamics simulations to study the binding modes of these antagonists. By utilizing these computational tools, we hope to identify efficient and selective C3aR antagonists that will serve as valuable lead compounds for drug development targeting the C3a receptor.

Project Keywords

Project Outline

Part 1 : Introduction to  C3a Receptor and Inflammation
• Overview of the C3a receptor and its role in inflammation
• Importance of targeting C3aR for anti-inflammatory therapy

Part 2 : Research Objectives and Hypotheses
• Development of novel, potent, and selective C3aR antagonists
• Enhancing the understanding of C3aR-ligand interactions through computational methods

Part 3 : Review of Existing Research and Technologies
• Current state of C3aR-targeted therapies and their limitations
• Overview of ligand design techniques and molecular dynamics simulations

Part 4:  Structural Analysis of C3a-C3aR Complex
• Detailed examination of the C3a-C3aR complex structure revealed by Cryo-EM
• Identification of key binding sites and interaction points

Part 5 :  Ligand Design and Docking Studies
• Using computational tools to design potential C3aR antagonists
• Performing ligand docking studies to predict binding affinities and modes

Part 6 : Molecular Dynamics Simulations
• Setting up molecular dynamics simulations to study the stability and dynamics of ligand-C3aR complexes
• Analyzing simulation data to refine ligand designs

Part 7:  Synthesis and In Vitro Testing
• Synthesizing the most promising C3aR antagonists
• Conducting in vitro assays to evaluate the binding affinity and selectivity of the synthesized compounds

Part 8: Optimization of Ligand Design
• Identifying key parameters affecting binding affinity and selectivity
• Using iterative design and testing to optimize antagonist properties

Part 9: Potential Applications in Anti-inflammatory Therapy
• Exploring the therapeutic potential of the developed C3aR antagonists
• Evaluating the benefits and challenges of using these antagonists in clinical settings

Part 10: Results and Discussion
• Presenting experimental and computational results
• Discussing the significance and potential applications of the research findings
• Comparing the new antagonists with existing C3aR-targeted therapies

Part 11: Conclusion and Future Research Directions
• Summarizing key findings and their importance
• Identifying research limitations and suggesting future research directions
• Proposing practical applications of C3aR antagonists in various fields

Part 12: Reporting and Presentation
• Writing a comprehensive research report with clear structure, concise language, and accurate data presentation
• Preparing and delivering an engaging oral presentation of the research background, methods, results, and conclusions

Suitable for

High School Students:  
• Interest in Biomedical Research: Students strongly interested in biomedical engineering, chemistry, and drug design.
• Basic Knowledge: Students with basic knowledge of biology, chemistry, and computational tools.

University Students:
• Relevant Major:  Students majoring in biomedical engineering, chemistry, pharmacology, or related fields.
• Technical Skills: Familiarity with molecular modeling software, ligand docking, and basic understanding of GPCRs.