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

Senthilkumar, B.; Rajasekaran, R.

doi:10.1007/s10989-016-9537-5

Cited by 10 publications

(8 citation statements)

References 56 publications

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“…Both the structures of Circulin A and Circulin B were energy minimized using YAMBER force field present in YASARA program . The obtained energy minimized structures were used for static structural analysis and for generating conformational ensembles for dynamic analysis …”

Section: Resultsmentioning

confidence: 99%

“…10,11,34 Previous studies analyzed the S─S bond distance of cyclic peptides and defined its structural constraint which, in turn, favored the stability. [36][37][38] It was noted that disulfide bonds inflict the geometrical constraints on protein backbones that plays a major role in the structural stability and functionality of proteins. 9…”

Section: Discussionmentioning

confidence: 99%

“…24 The obtained energy minimized structures were used for static structural analysis and for generating conformational ensembles for dynamic analysis. [36][37][38][39][40]…”

Section: Retrieval Of Data Structurementioning

confidence: 99%

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

Balaraman

Rajasekaran

2018

J of Cellular Biochemistry

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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.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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

Balaraman

Rajasekaran

2018

J of Cellular Biochemistry

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“…Based on the conservation of Cys residues and modelling studies [39], the knottin topology is expected to be retained across the Class B Evasins. Notably, the cystine knot is likely to increase the structural, proteolytic, and chemical stability of these proteins, enhancing their potential clinical utility [50]. Knottins have diverse biological activities ranging from protease inhibition to ion channel blockade [51].…”

Section: Structure Of Eva-3mentioning

confidence: 99%

Evasins: Tick Salivary Proteins that Inhibit Mammalian Chemokines

Bhusal

Eaton

Chowdhury

et al. 2020

Trends in Biochemical Sciences

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“…In the case of drug resistance, computations of shape complementarity—between either widely used or promising new drugs and a binding pocket of a protein altered by an SNP—bring together the advantages of protein structure (or dynamics) simulations and the ability to dock one structure with another [ 33 ]. Finally, the alignment of multiple protein structures and/or sequences holds a key to the above calculations for comprehensive SNP analysis of protein-coding gene regions [ 34 ]. Meanwhile, the smallest progress was observed with regulatory SNPs because their manifestations may vary from cell to cell, from tissue to tissue, from patient to patient, and from subpopulation to subpopulation [ 26 ].…”

Section: Introductionmentioning

confidence: 99%

Candidate SNP Markers of Chronopathologies Are Predicted by a Significant Change in the Affinity of TATA-Binding Protein for Human Gene Promoters

Пономаренко

Рассказов

Суслов

et al. 2016

BioMed Research International

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Variations in human genome (e.g., single nucleotide polymorphisms, SNPs) may be associated with hereditary diseases, their complications, comorbidities, and drug responses. Using Web service SNP_TATA_Comparator presented in our previous paper, here we analyzed immediate surroundings of known SNP markers of diseases and identified several candidate SNP markers that can significantly change the affinity of TATA-binding protein for human gene promoters, with circadian consequences. For example, rs572527200 may be related to asthma, where symptoms are circadian (worse at night), and rs367732974 may be associated with heart attacks that are characterized by a circadian preference (early morning). By the same method, we analyzed the 90 bp proximal promoter region of each protein-coding transcript of each human gene of the circadian clock core. This analysis yielded 53 candidate SNP markers, such as rs181985043 (susceptibility to acute Q fever in male patients), rs192518038 (higher risk of a heart attack in patients with diabetes), and rs374778785 (emphysema and lung cancer in smokers). If they are properly validated according to clinical standards, these candidate SNP markers may turn out to be useful for physicians (to select optimal treatment for each patient) and for the general population (to choose a lifestyle preventing possible circadian complications of diseases).

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

Cited by 10 publications

References 56 publications

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

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

Evasins: Tick Salivary Proteins that Inhibit Mammalian Chemokines

Candidate SNP Markers of Chronopathologies Are Predicted by a Significant Change in the Affinity of TATA-Binding Protein for Human Gene Promoters

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