Analysis of Binding Affinity in Drug Design Based on an Ab-initio Approach
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Computational methods are a convenient resource to solve drawbacks of drug research such as high cost, time-consumption, and high risk of failure. In order to get an optimum search of new drugs we need to design a rational approach to analyze the molecular forces that govern the interactions between the drugs and their target molecules. The objective of this project is to get an understanding of the interactions between drugs and proteins at the molecular level. The interaction energy, when protein and drugs react, has two components: non-covalent and covalent. The former accounts for the ionic interactions, the later accounts for electron transfer between the reactants. We study each energy component using the most popular analysis tools in computational chemistry such as docking scoring, molecular dynamics fluctuations, electron density change, molecular electrostatic potential (MEP), density of states projections, and the transmission function. We propose the probability of transfer of electrons (transmission function) between reactants in protein-drug complexes as an alternative tool for molecular recognition and as a direct correlator to the binding affinity. The quadratic correlation that exists between the electron transfer rate and the electronic coupling strength of the reactants allow a clear distinguishability between ligands. Thus, in order to analyze the binding affinity between the reactants, a calculation of the electronic coupling between them is more suitable than an overall energetic analysis such as free reaction energy.
density of states
molecular electrostatic potential
electron density change
Salazar Zarzosa, Pablo F. (2009). Analysis of Binding Affinity in Drug Design Based on an Ab-initio Approach. Master's thesis, Texas A&M University. Available electronically from