Background and Objective: Global increase in microbial infections has steered the production and improvement of antimicrobial and antifungal peptide drugs in pharmaceutical firm. In this study, structural stability of the antifungal peptide tachystatin B1 (2DCV) and B2 (2DCW) of Tachypleus tridentatus was computationally investigated. Materials and Methods: Static structure analysis showed high number of intra-molecular interactions in tachystatin B2 than B1 comparatively. Further, conformational sampling studies revealed tachystatin B2 to be structurally stable, substantiated by various structural events like root mean square deviation, ramachandran plot, radius of gyration, ovality and lipophilicity. Results: Moreover, the statistically validated contours of surface area, polar surface area, non polar surface area, hydrogen bond distribution and intra distance of disulfide bridges also supported the priority of tachystatin B2 with respect to stability. Conclusion: In this study, it is proposed that tachystatin B2 could be an efficient template for scaffolding antifungal peptide drugs. © 2016 B. Senthilkumar and R. Rajasekaran.

Rajasekaran R

Department of Biotechnology

School of Bio Sciences and Technology

Vellore Campus

Senthilkumar B

Vellore Institute of Technology (VIT) is a private university located in&nbsp;Tamil Nadu, India. Founded in 1984, as Vellore Engineering College, the institution offers 20 undergraduate, 34 postgraduate, four integrated and four research programs. It has campuses in Vellore, Amravati, Bhopal and Chennai.

VIT is one of the top ranked private universities in India according to NIRF, THE and QS Rankings.&nbsp;Govt. of India has recognized&nbsp;VIT, Vellore as an&nbsp;Institution of Eminence. This has allowed VIT to take independent quality initiatives and move up in world ranking.

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VIT University

Trends in Bioinformatics

Computational methods have refined the mode of peptide drug designing to a new plateau recently. Circulin, a 30 residue natural plant polypeptide acts as a plant defensive peptide. Additional to its antimicrobial activity it also possesses an inhibitory cytopathic effect on the replication of human immunodeficiency virus (HIV). Stable Circulin can be a functionally able template for scaffolding peptide based drugs. Hence, structural stability of Chassalia parvifolia, Circulin A (1BH4), and Circulin B (2ERI) was computationally investigated. From this analysis, the stability favored toward Circulin B which was supported by various parameters such as intra-molecular interactions (61), secondary structure, hydrophobicity (67.34%), root mean square deviation (2.64Å), root mean square fluctuation (0.08Å), radius of gyration (8.96Å), ovality (3.49), angular deviation (73.6%), surface area (both polar and non-polar), hydrogen bond distribution (11.94), and disulphide bond distances. Further, the functional activity calculated in terms of membrane associated free energy (-4.10 kcal/mol) also favored Circulin B. Hence, Circulin B could be proposed as the best template for scaffolding antimicrobial as well as antiviral (HIV) peptide based drug design. The obtained computational data can aid experimental biologists to successfully produce stable therapeutic peptides from natural resources reducing erroneous wastage of monetary sources and time.

Journal of Cellular Biochemistry

The structural and functional reliability of Circulins of Chassalia parvifolia for peptide therapeutic scaffolding

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 computationally studied to analyze their structural stability and functionality. Computational analysis like, intra-molecular interactions (25), relative stability (3.22) and instability index (−14.28) showed an increase in structural stability of native CA–MA hybrid. Additionally, the generated peptide ensembles showed a RMSD (3.98 Å), RMSF (0.202 Å), radius of gyration (11.98 Å), 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 functional 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. © 2017, Springer Science+Business Media New York.

Journal	Trends in Bioinformatics
Publisher	Science Alert
ISSN	1994-7941
Open Access	No