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Conformational profile assessment of Human cathelicidin (ll-37) and it's function as neutrophil apoptosis via the activation of FPRL1, explained using Molecular dynamics Simulations. Parul Sharma1, Roopali Verma2, Punit Kaur1 1Department of Biophysics, All India Institute of Medical Sciences, New Delhi, 2Jamia Milia Islamia University, New Delhi Cathelicidins are one family of cationic antimicrobial peptides (AMP), frequently α-helical, amphipathic host defense peptides and provide the first-line defense against infection by serving as “natural antibiotics”. Peptides are highly flexible in nature and fold at fast rates hence require probing at nanosecond time scale and molecular dynamics (MD) simulations provide detailed information on the fluctuations and their affect. The present study attempts to get a deeper insight into the conformational features of cathelicidin focused at establishing structure-activity relationships and investigates the propensities of cathelicidin to adopt different conformations by using different computational protocols. Two sets of 100 ns long MD simulations were carried out on the extended structure of cathelicidin using two different force fields AMBER ff96 and AMBER ff99. The MD simulations were performed at 300K using Langevin thermostat and Onufriev, Bashford and Case (OBC) implementation of the Generalized Born (GB) approximation. Dielectric constant in the peptide was set to 1 while an external dielectric constant of 80 was employed. All calculations were carried out using AMBER 12. The analysis of the trajectories was carried out using the ptraj module in AMBER and CLASICO software. The results suggest that the peptide adopts different conformations with respect to the force fields applied. Under the effect of AMBER ff99 antiparallel β- sheet conformation was sampled which is being stabilized by polar hydrogen bonds between residue Phe18 and Ile21. Large aromatic residues like, Phe and β-branched amino acids Ile are favored to be found in β strands and such antiparallel β sheets in antimicrobial peptides have been reported. Most cationic peptides adopt an amphipathic alpha-helical conformation upon binding to lipids hence in accordance to the NMR structure submitted in PDB (26KO) a helix-bend-helix motif spanning residues 4–31 followed by a disordered C-terminal tail was observed when force field AMBER ff99 had been applied. These contrasting results indicates that cathelicidin can fold in different conformations apart from the one reported which can be responsible for different activities and can be therapeutically relevant opening up newer avenues for the development of more potent drugs that specifically target the cell membrane of cancer cells with lesser side effects. Various conformations obtained by cluster analysis were used to carry out the binding study between Cathelicidin with fprl1, which could help us to understand the probable conformation of LL37 in which it can bind to the fprl1 receptor and carry out it's function.