Molecular docking calculations are essential for structure-based drug discovery because they facilitate the rapid identification and evaluation of prospective medicines. Using scoring systems, drug candidates are screened and ranked according to their ability to bind to a target. Frequently, this is the only viable method, as there are insufficient experimental data for alternative procedures. Due to the complexity of the binding process, however, scoring algorithms may incorrectly rank certain molecules. A flawed scoring mechanism can therefore result in erroneous conclusions. <br/>Classical scoring functions calculate the binding energy by adding the electrostatic and van der Waals interactions. A Coulombic formulation is used to determine the electrostatic terms. Generally, a distance-dependent dielectric function is utilized to regulate the contribution of charge-charge interactions, as point charge calculations pose difficulties when simulating the protein's native environment. A Lennard-Jones potential function characterizes the van der Waals (vdW) terms. Adopting alternative parameter values for the Lennard-Jones potential can alter the "hardness" of the potential, which determines the permissible degree of proximity between protein and ligand atoms. This distance is utilized to manage non-bonded contacts. In addition, this reduces the precision of binding's long-range effects. <br/>Consequently, the current scoring function employed by DOCK is the total of the pairwise electrostatic and van der Waals interactions between the ligand and the protein, as well as the ligand desolvation component. Calculating the potential energy of the rigid system when the ligand is strongly bound to the protein and estimating other effects by merely desolvating the ligand using the implicit water model. However, the actual binding procedure is far more intricate. Eventually, my new scoring function will implement in DOCK the receptor and ligand entropy loss and desolvation effects.<br/>This new scoring function solves the ranking problem and thus will make a breakthrough in computational drug design and help to find de-novo small-molecule drugs.

Using novel physical, computational, and chemical approaches to improve the scoring function in molecular docking

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