Development of Transferable Coarse-Grained Models of Amino Acids

There are twenty standard amino acids that are the structural units of biomolecules and biomaterials such as proteins and peptide amphiphiles (PAs). The focus of this study was to develop accurate transferable coarse-grained (CG) models of those amino acids. In CG models, several atoms are represented together as a single pseudo-atom or "bead," which can allow the modeling of processes like self-assembly of biomolecules and biomaterials through reduction of degrees of freedom and corresponding increased computational speed. A 2:1 to 4:1 mapping scheme, in which a CG bead is comprised of two to four heavy atoms, respectively, and associated hydrogens, has been employed to represent functional groups in the amino acids. The amino acid backbone atoms are modeled as two beads while the side chains are modeled with one to three beads, and each terminus is modeled as one bead. The bonded parameters for the CG models were obtained from bond, angle, and dihedral distributions from all-atom molecular dynamics (MD) simulations of dipeptides. Non-bonded parameters were optimized using the particle swarm optimization (PSO) method to reproduce experimental properties (heat of vaporization, surface tension, and density) of analogues of the side chains, termini, and backbone groups of the amino acids. These CG models were used to study the self-assembly pathways and mechanisms of the PA c16-AHL3K3-CO2H in the presence of explicit CG water.