Drug Designing: Open Access
Open Access

Principle and Applications of Structure Based Drug Design

^*Correspondence: Aslan Peter, Department of Pharmacy, National Autonomous University of Mexico, Mexico City, Mexico, Email:

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Description

Structure-Based Drug Design (SBDD) is a powerful approach used in the development of new drugs. SBDD involves the use of three-dimensional structures of biological macromolecules, such as proteins or nucleic acids, to guide the design of molecules that can bind to the target protein and modulate its activity.

Principles of Structure-Based Drug Design (SBDD)

SBDD is based on the principle of lock-and-key binding, where a drug molecule binds to a specific site on the target protein, much like a key fits into a lock. The binding of the drug molecule to the target protein can either activate or inhibit the protein's function, depending on the nature of the interaction. The first step in SBDD is to obtain the three-dimensional structure of the target protein. This can be done using techniques such as X-ray crystallography, NMR spectroscopy, or cryo-electron microscopy. Once the structure of the target protein is known, the next step is to identify small molecules that can bind to the protein and modulate its activity.

Molecular docking is a computational technique used to predict the binding of small molecules to the target protein. In molecular docking, a library of small molecules is screened for their ability to bind to the target protein's binding site. The molecules that show the best fit are then selected for further testing. Structure-activity relationship (SAR) analysis is used to optimize the binding of the selected molecules to the target protein. SAR analysis involves modifying the chemical structure of the molecules and testing their activity against the target protein. By comparing the activity of the modified molecules to the original molecule, SAR analysis can identify the key features of the molecule that are important for binding to the target protein.

Applications of SBDD

SBDD has been successfully applied in the development of drugs for a variety of diseases. One notable example is the development of protease inhibitors for the treatment of HIV. HIV protease is an enzyme that plays a crucial role in the replication of the virus. SBDD was used to design small molecules that could bind to the active site of the protease and inhibit its activity, thereby preventing the replication of the virus. This approach has led to the development of drugs such as saquinavir and ritonavir, which are widely used in the treatment of HIV.

SBDD has also been used in the development of cancer drugs. Cancer cells often have mutations in their DNA that result in the overexpression of certain proteins, which can drive tumor growth. SBDD has been used to design small molecules that can bind to these overexpressed proteins and inhibit their activity, thereby slowing or stopping tumor growth. Examples of cancer drugs developed using SBDD include imatinib, which targets the Bcr-Abl protein in chronic myeloid leukemia, and vemurafenib, which targets the BRAF protein in melanoma.

Conclusion

Despite its success in drug discovery, SBDD is not without its challenges. One of the main challenges is the limited availability of high-resolution structures of target proteins. Obtaining highresolution structures can be time-consuming and expensive, and not all proteins can be crystallized. In addition, not all proteins have well-defined binding sites, which can make it difficult to identify small molecules that can bind to the protein. Another challenge is the need for accurate computational methods for molecular docking and SAR analysis. These methods are still being developed, and their accuracy can be affected by factors such as the flexibility of the protein and the solvation effects of the binding site.