The word “docking” means anchoring. When we talk about Molecular Docking, our goal is to examine the interaction between two different molecules. In fact, during this software process, the interaction between two different molecules is analyzed and studied. Depending on the goal we have, we consider the best and most stable interaction mode for further studies.
Molecular Docking benefits
So what does this mean? This means reducing the risk of wasting time and capital while producing a drug molecule, vaccine, non-composite protein, aptamer, and many other cases in the laboratory. The purpose of such simulations is to achieve a clear view of the experiment. For example, a person spends several months in a simulated environment before going to space. The necessary training is transferred to him/her, and the existing conditions and various factors are analyzed and studied.
If such a process is not performed, what percentage of success is there during the main launch? Now, suppose you are a student, and you intend to work on developing a vaccine. Unfortunately, your thesis budget is severely limited. You may be a researcher who has thought of producing a non-composite protein for a long time. Examining your chances of success is the key to your success. Or do you prefer to start working in the laboratory on Monday?
The importance of molecular docking Today, bioinformatics studies and software simulations have become one of the top priorities of significant biotechnology companies worldwide. In these companies and with the help of experts in this field, everything is analyzed and simulated before entering the laboratory phase. When you can examine the effectiveness of a drug on its protein target in a few days, why spend millions of dollars on trial and error? One of the important features of the molecular docking technique is its comprehensiveness. This means that you are not limited to a specific field with mastery of this technique. Today, you can study the effectiveness of a small molecule in inhibiting a protein receptor. Or you can analyze and study the interaction of the S protein of the coronavirus with ACE2 tomorrow.
Attention! However, the important point during such software studies is your thinking. How valuable can it be to be an operator and perform a software process with a few simple clicks? The initial molecular docking algorithms were based on Emil Fischer’s lock-and-key theory, which was introduced in 1894. According to this theory, the determining factor in the connection of a ligand to its receptor is the shape of the binding site on the receptor. The connection occurs when the ligand and the binding site are paired.
Of course, this theory has moved towards induced fit in later years. According to this theory, during the binding process, the ligand causes conformational changes in the receptor. The power and accuracy of predicting the interaction between two molecules by molecular docking technique is increasing daily. Nothing can prevent the development of related software and platforms.
Methods of Molecular Docking
Molecular docking can be divided into two main steps: sampling and scoring. Sampling generates and explores different ligand poses in the protein binding site while scoring evaluates and ranks the poses according to their scores.
Various algorithms and strategies for sampling and scoring can be classified into different categories based on their complexity, flexibility, and accuracy. Some of the common categories are:
What are the different types of molecular docking studies?
Rigid docking: This is the simplest and fastest type of docking, where both the ligand and the protein are treated as rigid bodies, and only their translational and rotational degrees of freedom are considered. Rigid docking can be helpful for screening large libraries of ligands, but it cannot account for the conformational changes and dynamics of the molecules upon binding.
Flexible docking: This is a more realistic and accurate type of docking, where the ligand and/or the protein can change their conformations and adapt to each other during the docking process. Flexible docking can capture the molecules’ induced fit and binding specificity, but it is also more computationally expensive and challenging than rigid docking. Different levels of flexibility can be introduced, such as side-chain flexibility, backbone flexibility, or ensemble docking.
Covalent docking: This is a particular type of docking where the ligand and the protein form a covalent bond at the binding site. Covalent docking can be helpful in designing irreversible inhibitors or modulators of protein function. Still, it requires additional information and parameters, such as the reaction mechanism, the bond type, and the bond length.
Hybrid docking: This type of docking combines different methods and techniques to improve the performance and accuracy of the docking process. Hybrid docking can involve integrating multiple scoring functions, incorporating experimental data, applying machine learning or artificial intelligence, or combining docking with other computational methods, such as pharmacophore modeling, molecular dynamics simulations, or quantum mechanics calculations.
Applications of Molecular Docking
Molecular docking has a wide range of applications in various fields of science and medicine, such as:
Drug discovery and design
Molecular docking can help to identify potential drug candidates, optimize their properties and activities, understand their mechanisms of action, predict their binding modes and interactions, evaluate their selectivity and specificity, assess their pharmacokinetics and pharmacodynamics, and avoid their adverse effects and toxicity.
Protein-protein interactions
Molecular docking can help study the structure, function, and regulation of protein-protein interactions, which is essential for many biological processes and pathways, such as signal transduction, gene expression, cell cycle, apoptosis, immunity, and disease.
Protein-DNA/RNA interactions
Molecular docking can help to investigate the interactions between proteins and nucleic acids, which are involved in many aspects of genome organization, expression, and regulation, such as transcription, translation, replication, repair, recombination, and epigenetics.
Protein-ligand interactions
Molecular docking can help explore the interactions between proteins and other ligands, such as carbohydrates, lipids, metals, cofactors, hormones, peptides, or natural products, which can modulate the activity and function of proteins in various ways.
Protein engineering and design
Molecular docking can help to design and engineer novel proteins or protein variants with desired properties and functions, such as improved stability, solubility, affinity, specificity, catalysis, or recognition.
Conclusion
Molecular docking is a powerful and versatile computational technique that can provide valuable insights and information about molecules’ structure, function, and interaction, especially in drug discovery and design. However, molecular docking is also a complex and challenging technique that requires careful and critical consideration and application of the principles, methods, applications, and challenges involved. Molecular docking is not a perfect or definitive technique but rather a complementary and supportive technique that can benefit from and contribute to other experimental and computational techniques in the field of molecular sciences. Molecular docking is a dynamic and evolving technique with much potential and promise for the future of science and medicine.
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