Compared with traditional molecular docking, inverse or reverse docking is used to identify the target of a given ligand in a large number of receptors. Reverse docking can be used to discover new targets for existing drugs and natural compounds, explain the molecular mechanism of drugs and relocate drugs to find alternative indications for drugs, as well as detect adverse reactions and toxicity of drugs. In reverse docking, the necessary process is similar to the forward docking method: preparing the data set, finding the ligand pose, scoring, and sorting complex structures.

Figure 1. Docking & reverse docking.

Overall solution

• The prerequisite for reverse docking is a collection of target structures with information about the potential ligand binding region. The correct construction of the target structure database is a key step to improve the accuracy and applicability of the reverse docking method.
• The molecular docking procedure used in the reverse docking process is similar to the conventional docking method. Many popular docking programs have been developed, such as GOLD, DOCK, AutoDock or Glide; some modifications have been made on their basis to make the whole process more efficient and accurate in calculation.

The general process of reverse docking to determine potential targets

Many studies have used reverse docking as the primary method or a secondary option for analyzing broad-spectrum targets related to small molecules. Through reverse docking, new disease targets can be determined, the molecular mechanism of substances can be explained, alternative indications for known drugs can be found through drug relocation, and adverse drug reactions and drug toxicity can be detected. The researchers chose specific reverse docking tools and servers to meet their specific conditions and purposes.

Our services

CD ComputaBio also provides you with:

• Molecule Docking Service
• Protein-Small Molecule Docking Service

CD ComputaBio's reverse docking is the primary method used in structure-based drug design. This technology is to place the ligand molecule in the position of the active site of the receptor molecule, and then in real time according to the principles of geometric complementation, energy complementation and chemical environment complementarity. We can evaluate how well the ligand interacts with the receptor and find the best binding mode between the two molecules. In drug design, the molecular docking method is mainly used to search for small molecules with good affinity with the receptor biomacromolecule from the small molecule database, and conduct pharmacological tests to discover new lead compounds. Please contact us to learn more about our molecular docking service.

Reverse Docking Service FAQs

• • Q: What are the key steps in reverse docking?

    • A: Proper construction of a database of target structures is a key step in improving the accuracy and applicability of reverse docking methods. Various target databases have been developed for reverse docking. In addition, defining the appropriate binding site for each protein is important for computational efficiency and accuracy of docking results. The binding site or binding pocket of a receptor is a specific region of the receptor that binds to a ligand to form an interaction.

  • Q: What are the applications of reverse docking?

    • A: Many studies have used reverse docking as a primary approach or as a secondary option to analyze broad-spectrum targets associated with small molecules. Reverse docking allows the identification of new disease targets, interpretation of molecular mechanisms of substances, finding alternative indications for known drugs through drug repositioning, and detecting adverse drug reactions and drug toxicity. Another potential application of reverse docking is in the chief discovery and optimization phase of the drug discovery cycle.

  • Q: What are the tools used for reverse docking?

    • A: The molecular docking procedure used in the reverse docking process is similar to the conventional docking method. Many popular docking procedures have been developed. Some modifications have been made on their basis to make the whole process more computationally efficient and accurate. Compared to conventional docking methods, the reverse docking process is computationally demanding because it has to deal with a large number of protein targets. The noise in the docking fraction produces false positives in target confirmation. In particular, the target dependence of the docking fraction is more critical in reverse docking than in forward docking.

  • Q: What is the significance of binding pockets in reverse docking?

    • A: A predefined binding pocket facilitates reverse docking because it reduces the time spent searching for the appropriate docking region between the ligand and the receptor. In many previous studies, binding pockets were usually defined by those residues having at least one heavy atom within a distance of the heavy atom of the ligand. There are two main ways to obtain binding pockets; one is to retrieve binding pockets from the Protein Data Bank (PDB) complex structure and the other is to use a binding pocket search program. An automated process for defining binding sites is ideal because of the large number of targets that need to be examined during the reverse docking process.