Fragment-based Approach to Design GPCR Ligand Service

G protein-coupled receptors (GPCR) are the largest family of cell surface receptors and arguably the most important family of drug targets. With the breakthrough of X-ray crystallography and cryo-electron microscopy technology, more than 300 GPCR-ligand complex structures have been publicly reported since 2007, covering about 60 unique GPCRs. Such a wealth of structural information will undoubtedly help target GPCR to carry out structure-based drug design.

Overall solutions

• Interaction mode analysis.



• CIP-based ligand design.



• Bioactivity test of candidate compounds.
• Molecular dynamics simulation and calculation of binding free energy.

Our process

The overall process of our fragment-based GPCR ligand design method is shown in Figure 1:

• The first step is to analyze the crystal structure of the GPCR-ligand complex to obtain CIP.
• Then, a library of fragment-residue interaction patterns was compiled based on the docking binding patterns of known GPCR ligands.
• After that, all interaction modes of the library are compared with the given CIP through similarity calculation. Choose these similar interaction patterns and keep the corresponding fragments.
• The adjacent fragments on the binding interface are then assembled into small molecule ligands that can bind to proteins. After a series of analysis and filtering, certain structures with representative skeletons are screened as candidate compounds from commercial compound libraries.

Figure 1. Flow chart of fragment-based GPCR ligand design. (1) Generate CIP from the GPCR-ligand complex structure; (2) Construct fragment-residue interaction pattern library from known GPCR ligands by molecular docking; (3) Fragment by calculation based on CIP similarity Search; (4) Assemble the searched fragments to design new structures; (5) Obtain candidate compounds from commercial compound libraries through similarity search.

Our services

Related Services:

• Structure-based Virtual Screening (SBVS) Service
• Reverse Virtual Screening
• 2D-QSAR Service
• 3D-QSAR Service

CD ComputaBio' fragment-based approach to design GPCR ligand service can significantly reduce the cost and labor of the subsequent experiments. Our services is a personalized and customized innovative scientific research service. Each project needs to be evaluated before the corresponding analysis plan and price can be determined. If you want to know more about service prices or technical details, please feel free to contact us.

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