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

• Published in: Journal of cellular biochemistry 2018-05, Vol.119 (5), p.3999-4008
• Main Authors: Balaraman, Senthilkumar, Ramalingam, Rajasekaran
• Format: Article
• Language: English
• Subjects: Antiinfectives and antibacterials; Antimicrobial activity; Antimicrobial agents; antimicrobial peptide; Antiviral agents; circulin; Computation; Computer applications; conformational sampling; Cyclotides - chemistry; Deviation; Drug development; Free energy; HIV; Human immunodeficiency virus; Hydrogen bonds; Hydrophobicity; Molecular interactions; Molecular structure; Natural resources; Peptides; Plant Proteins - chemistry; Protein structure; Protein Structure, Secondary; Reliability engineering; Rubiaceae - chemistry; Scaffolding; Secondary structure; stability; Stability analysis; Structural reliability; Structural stability; Structure-Activity Relationship; Structure-function relationships; Viruses
• ISSN: 0730-2312; 1097-4644
• DOI: 10.1002/jcb.26557

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. A computational comparative study was performed among circulin cyclic peptides to determine their stability for peptide drug designing. The results offer a broad perspective on the dynamical stability of cyclotides. Disulphide bond length, secondary structure distribution, and free energy across membrane are shown to influence stability. The parametrical results offer new clues in designing stable circulin peptide drugs.