Modeling the biomolecular self-assembly and interaction

Mu, Xiaojia
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What materials designers most envy is nature’s building design. It has long been a dream for scientists to mimic and further engineer the behaviors, interactions, and reactions of biomolecules beyond experimental limits. To interpret and facilitate novel materials’ design, a hierarchical approach is presented in this dissertation. With the advent of molecular modeling, many biomolecular interactions can be studied. Using both computational and experimental approaches, we investigated the self-assembly of fluorenylmethoxycarbonyl-conjugated dipeptides (which are called “biomimetic materials”) including Fmoc-dialanine (Fmoc-AA) and Fmoc-Alanine-Lactic acid (Fmoc-ALac) molecules. We simulated the assembly of Fmoc-dipeptides and compared with experiments. We illustrated not only the angstrom-scale self-assembled structures, but also a prevalent polyproline II conformation with β-sheet-like hydrogen bonding pattern among short peptides. Further, simulations to calculate the potential of mean force (PMF) and melting temperatures were performed to gain deeper insights into the inter-fibril interaction. An energetic preference for fibril-fibril surface contact was demonstrated for the first time, which arises from a fibril-level amphiphilicity. From our study, a hierarchical self-assembly process mediated by the balance between hydrophobicity and hydrophilicity of fibril structures was unveiled. The next major topic in this dissertation involves the development of a chemically accurate polarizable multipole-based molecular mechanics model with the investigation of a series of chloromethanes. The ability of molecular modeling to make prediction is determined by the accuracy of underlying physical model. The traditional fixed-charge based force field is severely limited when applied to highly charged systems, halogen, phosphate and sulfate compounds. Via a sophisticated electrostatic model, an accurate description of electrostatics in organochlorine compounds and halogen bonds were achieved. Our model demonstrated its advantages by reproducing the experimental density and heat of vaporization; besides, the calculated hydration free energy, solvent reaction fields, and interaction energies of several homo- and heterodimer of chloromethanes were all in good agreement with experimental and ab initio data.