Molecular docking | Introduction to basic computational chemistry method | drug-target interaction

so hi everyone welcome to the science addicted channel i am a pharmacist by education with a passion for computational chemistry and data science and today i'm going to talk about what is molecular docking in the world of chem informatics as a disclaimer i would like to highlight that this is just an introduction video so molecular docking is a method which predicts the preferred binding position of one molecule which is usually called a ligand to a second one which is usually called the receptor docking can be done with small ligand molecules like the one presented here

but can also be done with peptides peptidomimetics rna dna the possibilities are really diverse but the bigger the ligand the more challenging it is to achieve trustworthy and accurate docking results receptors on the other hand are 3d structures of proteins which are usually published in the protein data bank but sometimes the 3d structure of the protein we want to study is not available and in these cases we can do homology modeling uh which is um on its own a whole different topic so let's clarify that uh docking is a computational method that has become a

widely used drug discovery tool especially in the academic communities due to its relatively low cost and also because of the perceived simplicity of use molecular methods have two key components on one hand the searching algorithm and the the on the other hand the scoring function so these two components work hand in hand to find the most stable binding confirmation of the two partners so um so the searching algorithm for clarity let's define that it is the component that it is responsible for exploring the searching space by making systematic changes to the molecule's orientation and conformation

there may there are many searching algorithms that developed some are more precise than others but all of them are meant to search within the conformational space for the more stable complex between the two partners scoring function on the other hand evaluates or as the name says scores the ligand conformations generated by the search algorithm so searching function oftentimes look intimidating at the first glance but really it is merely composed by summing basic bonding and non-bonding parameters of the two molecules composing the complex so really understand and analyze the obtain result it is important to be

familiar with the scoring functions of the docking software we use most scoring functions are very similar in concept but have different levels of simplifications and differ different variation of molecular mechanism mechanics force field that are used and estimate the energy of the pose within the binding site so the complexes calculated using molecular docking techniques can be more or less stable depending on various factors but the binding affinity calculated with the scoring function can be a good indicator of the binding strength and the stability usually high negative volume indicates a strong binding energy between the investigated

ligand and the receptor a positive value on the other hand would mean artifact clash or repulsion between the atoms of participating molecules in the docking experiment however a positive scoring value it is highly unlikely docking programs are fairly robust in this regard and they will eliminate any unrealistic poses uh from the final list of ligand solutions so after calculating the binding position between the ligand and the receptor the main purpose so is to study the interaction between the molecules at a precise atomic level and in this way docking methods allow screening of entire libraries um

which with a much lower cost than lab experi experiments and also allow a precise dog development and lead optimization i really hope you found this introductory course useful and i can't wait to see you on my next video which is planned to be some practical tips and tricks on how to set up a docking experiment and how to evaluate the results thank you