Unveiling Drug Discovery Insights Through Molecular Electrostatic Potential Analysis

Abstract

Molecular electrostatic potential (MESP) analysis has emerged as a pivotal tool in drug discovery, providing insights into molecular reactivity and noncovalent interactions essential for drug function. While widely used MESP-on-isodensity surface analysis offers interpretations of electron-rich or deficient regions of a drug molecule, the MESP topology parameters such as spatial minimum (V_min) and MESP at nuclei (V_n) provide a quantitative understanding. The investigation into the correlation between MESP parameters and various molecular properties such as lipophilicity, pK_a (acidity/basicity), conformations, and tautomeric forms is crucial for understanding the impact on biological activity of drugs and facilitating drug design. Moreover, MESP topology analysis serves as a fundamental tool in elucidating the pharmacological behavior of compounds and optimizing their therapeutic efficacy. A quantitative study utilizing V_n parameters to assess the hydrogen bond propensity of a drug presents a novel strategy for investigating drug-receptor interactions with increased precision. The qualitative and quantitative analysis of the MESP features of various drugs, including their applications in cancer, tuberculosis, tumors, inflammation, and infectious diseases such as malaria, bacterial infections, fungal infections, and viral infections, is conducted in this review.