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.

Rajasekaran R

Department of Biotechnology

School of Bio Sciences and Technology

Vellore Campus

Senthilkumar B

Kumar P

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 Cellular Biochemistry

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.

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

Recent emergence of plant derived peptide cyclotides, characterized with a cyclized head-to-tail backbone and three disulfide bonds forming cyclic cystine knot, has advanced the field of biopharmaceutics to next level. This conserved structural feature of cyclotides holds responsible for its outstanding resistance towards thermal, chemical and enzymatic degradation. Besides, the cyclotides are preferred widely in current research to develop them as potent peptide therapeutics, where the improvement of structural stability is a demanding task in pharmaceutical firm. Hence, in this work, the structural stability of six cyclotides of kalata family (kalata B1, kalata B2, kalata B5, kalata B7, kalata B8 and kalata B12) was investigated. Among all, maximum number of intra-molecular interactions was observed only in kalata B1 (kB1). In addition, geometrical observables using conformational sampling of six kalata cyclotides also revealed that kB1 exhibited statistically significant structural stability in terms of contours of root mean square fluctuation, gyration radius, ovality and surface area (polar and non-polar). Furthermore, the distance of disulfide bridges (S–S within 2.2 Å) also confirmed that kB1 achieved maximum strength in terms of structural stability and accomplished remarkable functionality in terms of ovality as compared to other five kalata cyclotides. Accordingly, kB1 could be demonstrated as a stable template for the advancement of peptide therapeutics. © 2016, Springer Science+Business Media New York.

International Journal of Peptide Research and Therapeutics

Analysis of the Structural Stability Among Cyclotide Members Through Cystine Knot Fold that Underpins Its Potential Use as a Drug Scaffold

Rapid increase in antibiotic resistance has posed a worldwide threat, due to increased mortality, morbidity, and expenditure caused by antibiotic-resistant microbes. Recent development of the antimicrobial peptides like viscotoxin (Vt) has been successfully comprehended as a substitute for classical antibiotics. A structurally stable peptide, Vt can enhance antimicrobial property and can be used for various developmental purposes. Thus, structural stability among the antimicrobial peptides, Vt A1 (3C8P), A2 (1JMN), A3 (1ED0), B (1JMP), and C (1ORL) of Viscus album was computationally analyzed. In specific, the static confirmation of VtA3 showed high number of intramolecular interactions, along with an increase in hydrophobicity than others comparatively. Further, conformational sampling was used to analyze various geometrical parameters such as root mean square deviation, root mean square fluctuation, radius of gyration, and ovality which also revealed the structural stability of VtA3. Moreover, the statistically validated contours of surface area, lipophilicity, and distance constraints of disulfide bonds also supported the priority of VtA3 with respect to stability. Finally, the functional activity of peptides was accessed by computing their free energy of membrane association and membrane interactions, which defined VtA3 as functionally stable. Currently, peptide-based antibiotics and nanoparticles have attracted the pharmaceutical industries for their potential therapeutic applications. Thereby, it is proposed that viscotoxin A3 (1ED0) could be used as a preeminent template for scaffolding potentially efficient antimicrobial peptide-based drugs and nanomaterials in future.

Applied Biochemistry and Biotechnology

In Silico Template Selection of Short Antimicrobial Peptide Viscotoxin for Improving Its Antimicrobial Efficiency in Development of Potential Therapeutic Drugs

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.

Journal of Bionanoscience

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

European Journal of Medicinal Chemistry

Cell-based peptide screening to access the undruggable target space

Drug Discovery Today

Peptide therapeutics: current status and future directions

PLoS ONE

On the Importance of the Distance Measures Used to Train and Test Knowledge-Based Potentials for Proteins

FEBS Letters

Forces stabilizing proteins

Journal of Molecular Graphics and Modelling

Computational study of protein secondary structure elements: Ramachandran plots revisited

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

Journal	Data powered by TypesetJournal of Cellular Biochemistry
Publisher	Data powered by TypesetWiley
ISSN	0730-2312
Open Access	No