Computational studies of Gramicidin-inspired peptides

Padhan, Rakesh (2021) Computational studies of Gramicidin-inspired peptides. Masters thesis, Indian Institute of Science Education and Research Kolkata.

Text (MS Dissertation of Rakesh Padhan (16MS178)) 16MS178_Thesis_file.pdf - Submitted Version Restricted to Repository staff only Download (3MB)

Abstract

The key aim of this thesis is to understand the folding properties of Gramicidin-inspired peptides having alternating L- and D-amino acids. Gramicidin is a 15-residue membrane-active peptide having alternating L and D-amino acids (Gramicidin A sequence: HCO-LVal-Gly-LAla-DLeu-LAla- DVal-LVal-DVal-LTrp-DLeu-LTrp-DLeu-LTrp-DLeu-LTrp-NH2CH2CH2OH) and its conducting form in membranous environment adopts beta helix conformation. This ionophoric antibiotic have also shown anti-cancer activities against metastatic breast and kidney cancer cell lines (Kasturee Chakraborty et. al Advanced Therapeutics 2018). Computational studies were performed using the Molecular Dynamics simulation approach in GROMACS package. Here we have designed gramicidin inspired octameric (8-mer) and hexadecameric (16-mer) peptides to examine the structural changes using Molecular Dynamics simulation approach. Since, gramicidin is having 15- amino acid residues, we choose to study the sequence-specific folding properties of peptide having 8 amino acid residues (half of the length of gramicidin) and 16 amino acid residues (having similar length of gramicidin) having alternating L and D-maino acids. We choose all Val, all Phe and all Trp residues to study the folding properties in order to evaluate the residue-specific structure formation. We studied LD8Val (peptide sequence: Boc - LVal - DVal - LVal - DVal - LVal - DVal- LVal – DVal- OMe) and LD16Val (peptide sequence: Boc - LVal - DVal - LVal - DVal - LVal - DVal- LVal - DVal- LVal - DVal- LVal - DVal LVal - DVal - LVal - DVal- OMe) to observe the folding properties peptides having alternative L and D-aliphatic amino acid residues. We studied LD8Phe (peptide sequence: Boc- LPhe - DPhe - LPhe - DPhe - LPhe - DPhe - LPhe - DPhe- OMe) and LD16Phe (peptide sequence: Boc- LPhe - DPhe - LPhe - DPhe - LPhe - DPhe - LPhe - DPhe- LPhe - DPhe - LPhe - DPhe - LPhe - DPhe - LPhe - DPhe- OMe) to observe the folding properties peptides having alternative L and D-aromatic amino acid residues. We studied LD8Trp (peptide sequence: Boc - LTrp - DTrp- LTrp - DTrp- LTrp - DTrp- LTrp - DTrp – OMe) and LD16Trp (peptide sequence: Boc - LTrp - DTrp- LTrp - DTrp- LTrp - DTrp- LTrp - DTrp - LTrp - DTrp - LTrp - DTrp - LTrp - DTrp - LTrp - DTrp – OMe) to observe the folding properties peptides having alternative L and D-amphipathic amino acid residues. Chapter 1 describes structural insights of Gramicidin and their environment-dependent conformations. In Chapter 2, describes the detailed computational methodology to understand the conformational features of gramicidin-inspired peptides. In Chapter 3 describes the results, discussion and conclusion of our study.

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