Membrane Proteins: Better Understand Your Drug Target
Membrane proteins (MPs) are a specific class of proteins found in living things that are connected to lipid domains and biological membranes. According to their partial, complete, or no association with the membrane, MPs are categorized as intrinsic proteins, transmembrane, and peripherally membrane-bound proteins (peripheral MPs-PMPs), which can affect communication, regulation, and structural coherence functions, such as the transport of bioactive molecules, immune system molecule recognition, ion transmission, and energy transmission. Numerous studies revealed that MPs were important drug targets for cancers, asthma, schizophrenia, and inflammatory diseases, and the studies and clinical trials for MPs produced a wealth of new medications and treatment options for a wide range of illnesses, including cardiovascular disease, psychiatric disorders, HIV/AIDS, and etc.
- G Protein-coupled Receptors (GPCRs)
GPCRs are also known as 7TMs, which refers to an architectural feature in which a protein alternately crosses the cell membrane seven times from the extracellular to the intracellular and back. Because they are the principal surface receptors for signal and minimal drug delivery, GPCRs have been the mainstay biological target for pharmacological therapy. As a result, there have been several studies concentrating on the processes of GPCRs and their biological functions, such as how they interact with medications. GPCRs are associated with various disorders. A total of 475 medications, or about 34% of those that the US FDA approved, are manually curated by scientists from the Clinical Trials database and other sources. These 475 pharmaceuticals act at GPCRs.
- Transporters
Transporters, also known as transport proteins, are found in biological membranes and are used to passively move ions, chemicals, or even proteins into or out of the cell. Transporters are intricate pumps and channel networks that traverse the cellular membrane. Pores, electron carriers, group translocators, active transporters, and other elements connected to transport networks are different types of transporters. Many diseases are relevant to transporters, such as cancer disease and psychiatric disease.
- Ion Channels
Ion channels act as a pore for ions like calcium, sodium, and potassium to pass through. Exogenous and endogenous ligands acting on ion channels control a wide range of cellular processes, for instance, therapeutic molecules bind to ion channels to treat disease. Additionally, several researchers have shown that ion channels are highly interesting candidates for medical research and drug development. Ion channels are more than 13% of drug targets in 7.9% of ligand-gated and 5.5 percent of voltage-gated ion channels, demonstrating their importance as drug targets and key players in the drug development process.
Fig.1 The Venn diagram of targets that belong to approved drugs binding targets according to the DrugBank. (Gong, 2019)
Membrane Protein Target and Drug Discovery
Numerous computational techniques have emerged to reduce the cost of acquiring suitable compounds as virtual screening or computer simulation in precision medicine has emerged as a useful way for drug discovery and drug design. Because the high-throughput screening method is expensive and time-consuming, computational tools are used in drug discovery to reduce the potential "hit compound" as well as to save money and time. As far as the researchers are concerned, DTI prediction contributes to the understanding of how pharmaceuticals or drug-like ligands operate on targets as well as drug reaction mechanisms and associated theory. The ligand-based approach, which has been effectively used to study both GPCRs and many other targets, adds value to biochemical data. Drug discovery uses a large amount of precise secondary and tertiary structural information as a result of the fast development of GPCR X-ray crystallography technology. As a result, the structure-based approach is also adopted and received significant advancements. We place a strong emphasis on talking about GPCR-ligand interaction and computer-based approaches to predict drug-membrane protein interactions.
The membrane protein is the research emphasis on understanding pharmacology and drug action. Creative Biolabs can shed light on crucial directions for future biomedical research as well as on particular disorders. The interaction of the drug pathway with other biological pathways and the physiological effects of the drug pathway must be further studied. The drug pathway's interaction network with other pathways will help researchers find new directions.
Reference
- Gong, J.; et al. Understanding membrane protein drug targets in computational perspective. Current Drug Targets. 2019, 20(5): 551-564.
