Abstract

PEPTIDES AS PHARMACEUTICAL LEADS: A MECHANISTIC BASED EXPLORATION THROUGH MOLECULAR MODELING AND DOCKING STUDIES

Ruchi Omar, Sweta Sharma, Veejendra K. Yadav and Arpita Yadav*

Abstract

In this study the pharmaceutical potential of naturally occurring antimicrobial peptides has been explored taking a mechanistic approach. The mechanistic aspects of their antifungal property and anti-HIV property have been studied in detail. The antifungal nature has been explained at the molecular level through their ion binding capacity. The antimicrobial peptides can bind to the HIV viral template by interactions other than base-pair base-pair type. A tight complex formation has been observed in molecular modeling and docking calculations. These fascinating properties of antimicrobial peptides have led to their exploration as pharmaceutical leads repeatedly but these compounds never gained success in the drug market due to their poor pharmacokinetics. Another added benefit of peptide leads is their capacity to curb microbial resistance issues. With these perspectives this study also investigates the ADME properties of these compounds and design of peptidomimetic leads with artificial backbone to enhance druggability. The importance of molecular modeling and docking studies in structural modification of antimicrobial peptides, design of peptidomimetic compounds with artificial backbone is also discussed. This work may guide experimentalists in the field to come up with non toxic, robust drugs for intertwined approach to deal with two fatal diseases HIV and internal fungal infection.

Keywords: antimicrobial peptide, anti-HIV, ion carriage, intermolecular interaction, docking, internal fungal infection, intertwined approach.