Apr 20th, 1:00 PM - 4:00 PM


Resistance is Not Futile: Computational Directed Design of Combatant Pentapeptides


The objective is to design novel antibiotics effective against methicillin-resistant Staphylococcus aureus (MRSA) using computer modeling and computational algorithms. Pentapeptide 128 when administered with oxacillin showed increase inhibition of penicillin binding protein 2a (PBP2a). Computer modeling was incited to explore the mechanism of action of the peptide. Autodock 4, a computer program that uses a Lamarckian Genetic Algorithm (LGA), was employed to predict free energy of binding between viable pentapeptides and PBP2a of MRSA. Pymol, a protein database (PDB) viewer, was used to visually record the results. Oxacillin, an antibiotic with a known binding affinity for MRSA, was used as a control for computational studies. Experimental evidence generated in the Cornell lab identified several pentapeptides that inhibited MRSA with efficacies ranges from 64.2 to 95.7%. Docking analysis of pentapeptide 128 (amino acid sequence: WCWKW) to PBP2a gave similar binding as oxacillin. An alternate binding site was discovered for oxacillin upon computer simulation of oxacillin and pentapeptide 128 concurrent binding. Pentapeptide 128 by itself is an inhibitor of MRSA to the same level of efficacy as oxacillin. Combined, oxacillin and peptide 128 seem to exhibit a synergistic mode of inhibition based on our in silico studies that can now be explored experimentally. The mechanism and a proposed role of pentapeptide 128 will be presented.