Abstract:
Bacterial infections have a large impact on population and the resistance to antibiotics is a severe problem affecting our ability to treat infective diseases. Within this scenario, the search of new molecules with antibacterial properties is invaluable. It has been reported that the digestion of a major milk protein called α-lactalbumin with proteases of the digestive tract, can provide a set of antibacterial peptides. Although the antibacterial activity of α-lactalbumin peptides has been proposed, their mechanism of action is still unknown since experimental techniques used to identify bacterial properties do not provide enough insights into the structural features mediating molecular activity. Computer simulations, on the other hand, can provide the structural dynamics of molecules at an atomic resolution helping identify the conformational states that mediate function. Thus, we aim to understand the molecular basis of the antibacterial properties of α-lactalbumin identified peptides using molecular dynamics simulations. Two peptides, generated through trypsin digestion, were reported to have antibacterial properties: LDT1 comprising residues 1 to 5 and LDT2 a disulphide-linked peptide (residues(17-31)S-S(109-114)). Interestingly, when mutating leucine to isoleucine in LDT2, the modified peptide (LDT2*) does not display any antibacterial activity. Chymotrypsin, on the other hand, produced only one antibacterial peptide LDC (residues(61-68)S-S(75-80)). Molecular dynamics (MD) simulations are herein used to sample the dynamics of LDT1, LDT2, LDT2* and LDC. By comparing the dynamical space of effective and non-effective peptides, we ultimately aim to understand the conformational features that drive antibacterial properties.
