Discovery of peptides used in protein therapeutics proposes treatment for a wide range of infectious and chronic human diseases. Therapeutically significant peptides are developed from naturally occurring peptides or through de novo design. The characteristic features like small size, high stability and structural compatibility with target proteins identifies peptides as a potential class of drug and novel antibiotics. Recent acceptance of computer-aided drug design involving computational methods and resources for design and discovery of new therapeutic solutions has rapidly increased. This review describes systematic identification of the most imperative data sources and computational applications in designing peptides with desired biological features and enhanced therapeutic importance in pharmaceutical and nanomedicine firm. In addition, the current challenges for designing a stable peptide with favorable physiologic properties and the ways to overcome these issues are discussed with successful examples from literature. Using this approach, several peptides having anti-cancer, anti-angiogenic, anti-inflammatory and anti-microbial activities have been designed and biologically characterized. Copyright © 2016 American Scientific Publishers.

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

Journal of Bionanoscience

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 of Cluster Science

Structural Stability Among Hybrid Antimicrobial Peptide Cecropin A(1–8)–Magainin 2(1–12) and Its Analogues: A Computational Approach

Computational Resources for Designing Peptide Based Drugs Preferred in the Field of Nanomedicine

Structural stability of Oldenlandia affinis cyclotide, kalata B1 of native (1NB1) and two mutants 2F2I ([P20D, V21K] kB1) and 2F2J ([W19K, P20N, V21K] kB1) was investigated. Single model analysis showed high number of intra-molecular interactions followed by more proportion of beta sheet contents in [P20D, V21K] kB1 as compared to that of native and the other mutant of kalata B1. Further, the modern conformational sampling approach, an alternate to classical molecular dynamics was introduced, which revealed that the [P20D, V21K] kB1 was identified as structurally stable one, substantiated by various structural events viz., root mean square deviation, root mean square fluctuation, and angular deviation by Ramachandran plot. Moreover, the statistically validated contours of polar surface area, hydrogen bond distribution and the distance of disulfide bridges also supported the priority of [P20D, V21K] kB1 with respect to stability. From this work, it is proposed that the [P20D, V21K] kB1 (2F2I) could be the best template for scaffolding peptide based drug design. J. Cell. Biochem. 117: 66-73, 2016. © 2015 Wiley Periodicals, Inc.

In-Silico Template Selection of In-Vitro Evolved Kalata B1 ofOldenlandia Affinisfor Scaffolding Peptide-Based Drug Design

Identification of functional significance of non-synonymous single nucleotide polymorphisms (nsS-NPs) is a promising area in human genetic variation that causes various diseases. In this study, the effect of nsSNPs in Btk (Bruton's tyrosine kinase) was investigated computationally by analyzing stability and efficiency of protein interactions. The consequence between the structural and functional relationship was contributed by substitution of conserved amino acid residue which leads to X-Linked Agammaglobulinemia (XLA). Hence, the most detrimental missense mutations in domains viz., PH (pleckstrin homology), SH2 (Src homology 2) and kinase domain of Btk were computationally identified. Out of 113 observed variants, 78 variants were commonly found to be less stable, deleterious and damaging by I-Mutant 2.0, SIFT and PolyPhen programs respectively. Subsequently, in-silico modeling was performed and RMSD (root mean square deviation) was computed for these 78 variants to understand the structural deviation with respect to three native domains of Btk.In addition, the native PH domain and its 13 mutants were docked with substrate, phosphotidylinositol 3,4,5-triphosphate (PI(3,4,5)P3). Similarly, the native SH2 domain and its 13 mutant were docked with its interacting partner, BLNK (B-cell linker protein). Also, the native kinase domain and its 52 variants were docked with its inhibitor, Dasatinib. Based on these computational analyses, it was observed that the majority of amino acids in mutants of PH and SH2 domain lost the interacting efficiency with their substrate, PI(3,4,5)P3 and BLNK respectively, whereas, Dasatinib was found as a potential inhibitor for several mutants of kinase domain which could be used for the treatment of imatinib-resistance chronic myelogenous leukemia (CML). Moreover this work could pave the way for aiding nanotechnology based targeted drug delivery. Copyright © 2015 American Scientific Publishers.

Computational Investigation to Explore the Detrimental Missense Mutations in Bruton's Tyrosine Kinase Aiding Nanotechnology Based Targeted Drug Delivery

Journal	Data powered by TypesetJournal of Bionanoscience
Publisher	Data powered by TypesetAmerican Scientific Publishers
ISSN	1557-7910
Open Access	No