Peptit bazlı nanomalzemelerin moleküler dinamik simulasyonlar aracılığı ile yapısal ve termodinamik özelliklerinin analizi

Peptides are oligomers with aminoacids as building blocks. Discovery of naturallyoccuring functional peptides has led to a dramatic increase in research for both under-standing of natural peptides as well as design of novel synthetic ones. As individualmolecules, peptides serve a variety of purposes: such as drugs, antigens, ligands andantibiotics. They also act as building blocks for self-assembled nanofibers, nanotubes,micelles, and monolayers. Designing novel peptide-based materials with desired prop-erties and functions can only be possible by understanding the link between sequence,structure and organization of these molecules.This thesis work is composed of four main sections. In the first study, we analyzedstructure and thermodynamics of small amphiphilic peptides that spontaneously formmonolayers at the air/water interface. We accurately calculated the free energy oftransferring peptides from bulk water to the air/water interface, and analyzed itscomposition. Next, in the light of information gathered from small amphiphilic pep-tides we analyzed folding of a carefully designed 24-residue amphiphilic peptide atthe air/water interface. We calculated free energy of adsorption, and decomposedit into enthalpic and entropic contributions. We determined key elements requiredto adapt the targeted ß-hairpin conformation and for adsorption at the interface viain-silico mutations. In addition, we also determined organization of ß-hairpins withinsurface monolayers, which will help improve design strategies for manufacturing such2-D structures. In the third study, we tried to understand self-assembly of tri-blockpeptides into nanofibers in bulk water. By substituting aliphatic residues with aro-matic ones located in the central block of these peptides, we analyzed the stabilityand strength of these fibers. We also investigated possible nucleation mechanisms forfiber formation, which can be used to design stable and functional peptide nanofibers.Investigation of material properties and bulk behavior of peptides requires moreefficient computational techniques. In this regard, finally, we investigated the ?trans-ferability? of a recently developed solvent-free coarse-grained (CG) peptide model [1]that was shown to capture quantitatively structural and thermodynamic propertiesof a hydrophobic di-phenlyalanine peptide (FF). By mimicking the CG mapping usedin the FF CG model and transferring bonded and nonbonded interaction potentialsto other hydrophobic di-peptides, namely valine-phenyalanine (VF) and isoleucine-phenylalanine (IF), we tested the generality of this CG model. We devised a generalprotocol to transfer the original CG model to other hydrophobic di-peptides, whichare in the form of XF, where X represents an arbitrary amino acid. Hydrophobic di-peptides are the smallest molecules forming self-assembled hierarchical structures inaqueous solution. Therefore, development of a transferable CG model for simulationof such systems will help elucidate the driving forces important in the self-assemblyof peptide-based materials and peptide aggregation.