Design of antimicrobial and anticancer peptides based on membrane and peptide biophysical properties

Peptides are a unique group of pharmaceutical compounds whose intrinsic function and nature in regulating the cellular and physiological processes of the human body have made it possible to mimic and benefit from these characteristics in the treatment and drug design. Therapeutics peptides due to their small size, ease of synthesis, ability to penetrate cell membranes, high activity, specificity and biological and chemical diversity are suitable candidates for the treatment of many diseases. Antimicrobial and anticancer peptides are a group of therapeutic peptides that in addition to antibacterial, fungal, and viral properties can affect the immune system and have an effective role in the removal of cancer cells. Due to the expansion of databases in the field of therapeutics peptides, the use of computational methods such as artificial intelligence and machine learning has made it possible to design and modify the performance of these peptides. The cell membrane is the first barrier to penetrate and binding the factors that cause cell destruction. Changing the membrane content and its physical properties determines how the therapeutics peptides interact with the membrane. The interactions between proteins and membranes play critical roles in signal transduction, cell motility, and transport, and they are involved in many types of diseases. Molecular dynamics (MD) simulations have greatly contributed to our understanding of protein–membrane interactions. In this study, the binding, penetration, and interaction ofnatural and designed antimicrobial and anticancer peptides with different membranes was investigated by the molecular dynamics simulation. All the simulations were run for at least ۲۰۰ ns using the GROMACS package and then peptide penetration in the membrane was evaluated by different analyses. The results show that the penetration rate, mechanism of action of the peptide, and interaction peptide with membrane depends on the characteristics of the peptide such as sequence length, hydrophobicity, charge, peptide orientation on the membrane, amino acidic composition, and its concentration. The lipid composition of different membranes, the presence of cholesterol in the membrane, and fluidity and symmetry in the membrane will be important factors affecting the interaction of peptides with membrane.

کلیدواژه ها:

molecular dynamics ، membrane ، therapeutics peptides ، penetration