Development of Transferable Coarse-Grained Models of Amino Acids

• Main Author: Conway, Olivia Kristine
• Other Authors: Chemical Engineering
• Format: Others
• Published: Virginia Tech 2019
• Subjects: CG-MD; protein
• Online Access: http://hdl.handle.net/10919/94320

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. === Master of Science === In this study, models of the amino acids were developed for computer simulations. In these models, the amino acids are represented as a collection of two or more “beads” bonded together rather than as a collection of atoms bonded together. The beads were created in such a way that their characteristics reflect those of the molecules and atom groups that they represent. This was accomplished in part by selecting parameters for each bead that approximately reproduce experimental properties (density, heat of vaporization, and surface tension) and structures (bonds and angles) of the molecules and atom groups of which they are representative. Amino acids can link together to form short segments, known as peptides, or longer chains that form proteins. The bead models that were developed in this study can be linked together in the same way. They can also be linked with other beads that represent other atom groups—carbon groups of a carbon chain, for example. Certain types of molecules known as peptide amphiphiles (PAs) are often composed of amino acids and a carbon chain. The amino acid bead models were created especially to study these molecules, so once the models were developed, they were used in computer simulations to represent PAs. Many types of PAs can automatically assemble into structures that resemble fibers, and it is this behavior in particular that was studied. By using these models in computer simulations, we are able to see things that cannot be seen in a lab with a microscope or other lab tools. This may help with future efforts to study and design molecules such as PAs which show promise for medical applications like drug delivery.