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Structure-based GPCRs Modeling

G protein-coupled receptors (GPCRs) mediate cellular responses to the majority of hormones and neurotransmitters, and are therefore attractive targets for drug discovery. In the past years, significant progress has been made in the structural biology of GPCRs, raising the possibility of applying structure-based approaches to GPCR drug discovery efforts. Creative Biolabs is dedicated to establishing the most exquisite service platform for our clients and our one-stop GPCRs modeling services can provide comprehensive technical support to promote your projects.

Introduction to Structure-based GPCRs Modeling

The superfamily of GPCRs refers to a broad range of proteins with a common architectural feature, a domain consisting of seven alpha helices (7 TM) which traverse the cell membrane alternatively from the extracellular (EC) side to the intracellular (IC) side and back again. The conserved topology of 7 TM is an important aid in the 3D modeling of GPCRs. When none or very few structures are available, a popular strategy to build 3D models of GPCRs is based on ab initio modeling of the 7 TM helices and subsequent packing onto the conserved 7 TM topology.

Currently, it has become commonplace to employ models of 7 TM proteins in drug discovery activities. Considerable protein flexibility ranging from the active site to the entire protein complex structure is common using molecular mechanics-based approaches. More accurate quantum chemical ab initio methods are possible for more accurate evaluations of, e.g., ligand-protein interactions. Additionally, in terms of complementing the increasing structural information on the involvement of explicit water molecules in various regions of GPCRs such as orthosteric sites or the sodium binding sites seen in A2aAR crystal structures, computational methods are now more reliably examining the various roles of these waters. Finally, the increased capabilities of GPCR modeling are opening up new types of opportunities such as the use of homology modeling of orphan receptors to identify ligands for use in de-orphanizing these receptors.

Overall structure of the human SMO receptor 7TM domain. Fig.1 Overall structure of the human SMO receptor 7 TM domain.

Services

Protein structures have contributed in two ways to drug development: guiding the optimization of lead candidates, and enabling the discovery of new chemical series, the latter using molecular modeling and related techniques. Despite the steady increase in the number of GPCR crystal structures, the reality is that the majority of receptors have yet unknown structure. In these cases, structure-based homology modeling remains one of the most important techniques for obtaining a reasonable 3D structural model to use in rational ligand design. We can offer a variety of GPCRs modeling services to meet specific customer requirements.

Creative Biolabs has focused on the development of computational protein design for years. With years of experience, we can whole-heartedly cooperate with you to accomplish our shared goals. Our team provides you with outstanding support and meets your specific needs based on our professional technology platform. If you are interested in our services, please contact us for more details.


All listed services and products are For Research Use Only. Do Not use in any diagnostic or therapeutic applications.

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