Theoretical investigation of antimicrobial property of native histatin-3 and four mutants of D1H, G23A, D1H+G23A and D1H+G9W via molecular Dynamics simulation method

Antimicrobial peptides represent one of the most promising future strategies for combating infections and microbial drug resistance that had positive charge [1]. Histatin-3 (HTN3) is a 32-amino acid rich in histidine, with low molecular weight cationic peptides synthesized by the salivary glands [2]. In this study, in order to investigate the antimicrobial activity of HTN3, its native and Asp1His, Gly23Ala, Asp1His+Gly23Ala and Asp1His+Gly9Trp mutants of this peptide in the presence of sodium dodecyl sulfate (SDS) micelle were subjected to molecular dynamics simulation. The structures were simulated once with SDS micelle and once without it. Simulations were performed by the GROMACS 5 under Amber99 force field and the TIP4P water model for 50 ns. Also binding free energy calculations were done by g_mmpbsa software. Analyses were carried out during the last 30 nanoseconds. The results of potential energy, RMSD, temperature, Rg, and SASA indicated that the systems reached to equilibrium. According to the results of MM/PBSA, the best structure, is Asp1His+Gly23Ala mutation because it has the least binding free energy to SDS micelle. Therefore it can be concluded that this peptide has the most antimicrobial activity rather than native and other mutated peptides. Also, the center of mass (COM) distance measurement between the SDS micelle and this peptide is less than the COM distance of the other structures so it indicates that the peptide is closer to the micelle.

Keywords:

Antimicrobial peptides , HTN3 , SDS micelle , MM/PBSA , molecular dynamics simulation