Interaction of camel Lactoferrin derived peptides with DNA: a molecular dynamics study

Abstract

Background Lactoferrampin (LFampin), Lactoferricin (LFcin), and LFchimera are three well-known antimicrobial peptides derived from Lactoferrin and proposed as alternatives for antibiotics. Although the intracellular activity of these peptides has been previously demonstrated, their mode of action is not yet fully understood. Here, we performed a molecular dynamics simulation study to understand the molecular interactions between camel Lactoferrin derived peptides, including CLFampin, CLFcin, and CLFchimera, and DNA as an important intracellular target. Results Our results indicate that all three peptides bind to DNA, albeit with different propensities, with CLFchimera showing the highest binding affinity. The secondary structures of the peptides, modeled on Lactoferrin, did not undergo significant changes during simulation, supporting their functional relevance. Main residues involved in the peptide-DNA interaction were identified based on binding free energy estimates calculated over 200 ns, which, as expected, confirmed strong electrostatic interactions between DNA phosphate groups and positively charged peptide side chains. Interaction between the different concentrations of CLFchimera and DNA revealed that after binding of four copies of CLFchimera to DNA, hydrogen bonds between the two strands of DNA start to break from one of the termini. Conclusions Importantly, our results revealed that there is no DNA-sequence preference for peptide binding, in line with a broad antimicrobial activity. Moreover, the results showed that the strength of the interaction between DNA and CLFchimera is concentration dependent. The insight provided by these results can be used for the rational redesign of natural antimicrobial peptides targeting the bacterial DNA.

Identification of cathelicidin gene from Hoplobatrachus rugulosus and the antioxidant capacity of PC29 peptide

“…5b). A recent report also revealed that Lys and Arg are main play an important role in camel Lactoferrin chimera-DNA complex with electrostatic interactions and particularly salt bridges [41]. In addition, hydrogen bonding was found between Ser13 residue and pyrimidine ring of thymine base (Fig.…”

Effects of adding poly-histidine tag on stability, antimicrobial activity and safety of recombinant buforin I expressed in periplasmic space of Escherichia coli

“…For in silico investigation of stability, the amino acid sequence of buforin I and recombinant buforin I, were modeled with I-TASSER server ( https://zhanggroup.org/cgi-bin/itasser ) using default parameters 40 . The quality of the models was examined with VADAR server ( http://vadar.wishartlab.com/ ) 41 .…”

“…For analysis of electrostatic potentials of predicted peptides, PyMol plug-in APBS tools were applied, and PDB2PQR and default grid set-tings were applied for the calculations 31 . The stability of peptides were analyzed using molecular dynamics simulation with the GROMACS 2016.1 package and GROMOS54a7 force field 40 was solvated in a cubic box using the Simple Point Charge (SPC) water model, for neutralizing the overall charge of the systems, Na + and Cl - ions were added as appropriate. The system was first energy minimized using the steepest descent algorithm to relax high-energy contacts.…”

“…After energy minimization, the system was simulated under the NPT ensemble for 150 ns, with initial velocities taken from a Maxwell Boltzmann distribution corresponding to 100 K. During this initial simulation time, the peptide was positionally restrained at the temperature was 310 K at 1 atm. The dynamics and stability of peptides under, including root mean square deviation (RMSD), root mean square fluctuations (RMSF), and radius of gyration (RG) were analyzed during the simulation using GROMACS built-in tools 40 .…”

Electrostatics-Based Computational Design and Experimental Analysis of Buforin II Antimicrobial Peptide Variants with Increased DNA Affinities

“…21−23 In previous work, we used a combination of molecular dynamics (MD) simulations and electrostatics calculations to characterize the interactions between BF2 and its potential nucleic acid targets, 23−25 an approach similar to others used to analyze DNA-binding affinity for various AMPs. 13,26,27 Here, we focus on developing a computational framework to predict BF2 arginine mutations that increase BF2 affinity to nucleic acids. Our framework builds on the assumption that the affinity between BF2 and nucleic acids is governed primarily by electrostatic interactions and that the rational substitution of a neutral residue with arginine at particular positions may predictably modulate BF2/DNA electrostatic binding affinity through changes in both monopole and charge distribution.…”