ORIGINAL PAPER Structural Stability Among Hybrid Antimicrobial Peptide Cecropin A(1–8)–Magainin 2(1–12) and Its Analogues: A Computational Approach B. Senthilkumar 1 • D. Meshach Paul 1 • E. Srinivasan 1 • R. Rajasekaran 1 Received: 15 November 2016 Ó Springer Science+Business Media New York 2017 Abstract Cecropin A–Magainin 2 (CA–MA) hybrid antimicrobial peptide (AMP), a combination of two naturally occurring AMPs, cecropin A and magainin 2 is preferred widely in biotechnological, nano and pharmaceutical applications. It exhibits a strong antibacterial activity with a characteristic reduced cytotoxic effect towards mammalian cells. In this study, three AMP structures native CA–MA hybrid and its tryptophan substitutes CA–MA L2 and CA–MA A2 was computa- tionally studied to analyze their structural stability and functionality. Computational analysis like, intra-molecular interactions (25), relative stability (3.22) and insta- bility index (-14.28) showed an increase in structural stability of native CA–MA hybrid. Additionally, the generated peptide ensembles showed a RMSD (3.98 A ˚ ), RMSF (0.202 A ˚ ), radius of gyration (11.98 A ˚ ), ovality (3.33) and hydrophobicity (69.7%) supporting native CA–MA along with hydrogen bond strength (-4.212 kcal/mol) and distribution comparatively. The distribution of secondary structure in native CA–MA hybrid showed the sequential maintenance of stable helical content along with helical stability (52.25%) and computed free energy (-1.74 kcal/mol) in membrane mimicking environment proving its func- tional activity comparatively. This study aids in designing stable AMP biodrugs with low cytotoxicity in future, the result can be potentially extended to other AMPs to assist in their exploitation as peptide and nano drugs. Keywords Cecropin Á Magainin Á Antimicrobial peptide Á Nano drug stability Á Conformational sampling & R. Rajasekaran rrajasekaran@vit.ac.in 1 Department of Biotechnology, School of Bio Science and Technology, VIT University, Vellore 632014, Tamil Nadu, India 123 J Clust Sci DOI 10.1007/s10876-017-1240-y