Application of 3D-QSAR for identification of descriptors defining bioactivity of antimicrobial peptides.
In our laboratory, a series of antimicrobial peptides have been developed, where the resulting 3D-physicochemical properties are controlled by the placement of amino acids with well-defined properties (hydrophobicity, charge density, electrostatic potential, and so on) at specific locations along the peptide backbone. These peptides exhibited different in vitro activity against Staphylococcus aureus (SA) and Mycobacterium ranae (MR) bacteria. We hypothesized that the differences in the biological activity is a direct manifestation of different physicochemical interactions that occur between the peptides and the cell membranes of the bacteria. 3D-QSAR analysis has shown that, within this series, specific physicochemical properties are responsible for antibacterial activity and selectivity. There are five physicochemical properties specific to the SA QSAR model, while five properties are specific to the MR QSAR model. These results support the hypothesis that, for any particular AMP, organism selectivity and potency are controlled by the chemical composition of the target cell membrane.
Bhonsle
Jayendra B
JB
Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA. jayendra.bhonsle@na.amedd.army.mil
Venugopal
Divakaramenon
D
Huddler
Donald P
DP
Magill
Alan J
AJ
Hicks
Rickey P
RP
D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry* / Q000494:pharmacology; D002462:Cell Membrane / Q000737:chemistry; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D016000:Cluster Analysis; D008433:Mathematics; D008958:Models, Molecular; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D009161:Mycobacterium / Q000187:drug effects; D021281:Quantitative Structure-Activity Relationship; D013211:Staphylococcus aureus / Q000187:drug effects; D055672:Static Electricity
D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides