Molecular insights into the self-assembly of short amphiphilic peptides F_mD_n and F_mK_n

Abstract

The self-assembly of short amphiphilic peptides F m D n and F m K n is investigated by molecular dynamics simulation. The peptides are composed of hydrophobic phenylalanine (Phe, F), as well as hydrophilic aspartic acid (Asp, D) and lysine (Lys, K), and described by a coarse-grained MARTINI force field. Within ms-scale simulation, FD and FK only form loose polymeric clusters. Upon increasing the length of Phe residues in F m D and F m K (m ¼ 2 to 4), larger and more stable micelles are formed. F m K and F m D prefer to assemble into quasi-spherical and sheet-like micelles, respectively. For F 3 K n (n ¼ 2 to 8) and F 6 K n (n ¼ 4 to 12), the assembly capability reduces leading to smaller micelles when the length of Lys residues increases. For the formation of quasi-spherical micelles with distinct core/shell structure, the optimal ratio of hydrophobic/hydrophilic residues is found to be 3/4 for both F 3 K n and F 6 K n . This simulation study provides molecular insights into the assembly process and mechanism of short peptides, and it could facilitate the development of new peptides with desired morphologies.

Amphiphilic Peptides A6K and V6K Display Distinct Oligomeric Structures and Self-Assembly Dynamics: A Combined All-Atom and Coarse-Grained Simulation Study

“…The assembly dynamics of large aggregates of A 6 K or V 6 K peptides was studied using the Martini coarse-grained model , implemented in GROMACS 4.5.3 software. This force field was parametrized in a systematic way, combining top-down and bottom-up strategies: nonbonded interactions are based on the reproduction of experimental partitioning free energies between polar and apolar phases of a large number of chemical compounds, whereas bonded interactions are derived from reference all-atom simulations. − The MARTINI model was also extensively parametrized for amino acids ,− and the interaction strength between side chain beads and backbone beads closely match atomistic reference models. , This CG model is widely used as an effective model for studying peptide self-assembly ,,,, and it extends the accessible simulation time scale significantly by employing a 4:1 heavy-atom/CG-bead mapping and a reduced water model. Each CG water bead corresponds to four water molecules.…”

“…57−60 The MARTINI model was also extensively parametrized for amino acids 54,58−60 and the interaction strength between side chain beads and backbone beads closely match atomistic reference models. 58,60 This CG model is widely used as an effective model for studying peptide self-assembly 19,33,34,61,62 and it extends the accessible simulation time scale significantly by employing a 4:1 heavy-atom/CG-bead mapping and a reduced water model. Each CG water bead corresponds to four water molecules.…”

The Martini Model in Materials Science

“…[ 229 ] Many groups have explored their self‐assembly process by leveraging the Martini model. [ 230–252 ] Besides allowing simulation of the self‐assembly and growth, Martini is also particularly suited for high‐throughput applications. An example of such a high‐throughput application in the area of peptide‐based supramolecular materials is the work of Frederix et al.…”

In SilicoSelf-Assembly of Nanoparticles with Applications in Drug Delivery

“…Increasing this ratio led to elliptical aggregates, whereas decreasing this ratio resulted in smaller and less stable micelles. 24 Three ionic peptides EAK16, containing the same 16 residues but different amino acid sequences, were studied by CGMD simulations in bulk solution or in the presence of a hydrophobic surface at different pH values. In bulk solution, two peptides showed aggregation into fibrillar structures at all pH ranges.…”