UC Davis

Molecular Modeling for 3D Printing and Biological Applications Abstract This dissertation covers several molecular modeling efforts applied across length and time scales. These techniques are primarily applied to two major categories: 3D printing (chapters 2-4) and biological applications (chapters 5-7). These computational efforts were part of a collaborative effort to improve the experimental design process for these two applications and have corresponding experimental validation. We first present the application of multi-scale simulation techniques to the process of controlled assembly, which is a critical pre-cursor to enabling 3D printing at the nano-scale. This controlled assembly process depends on the complex interplay between surface, solute, and solvent interactions during the evaporation process. In order to actually model the assembly that takes place during this evaporation process a computational software and methodology had to be developed to replicate evaporation of mixed solvent systems and account for potential hydrogen bonding shells. This resulting methodology was tested for different evaporation rates and scales and is presented in Chapter 2. Chapters 3 and 4 are application papers using this methodology. Chapter 3 focuses on the assembly of small linear sugar molecules analyzed using atomistic molecular dynamics simulations. This atomistic resolution allows the probing of phase transitions these sugars undergo as they assemble into various morphological structures during evaporation. Chapter 4 focuses on the coarse-grained interactions between the phospholipid POPC, various surface types, and mixed solvents. This work investigated the specific contributions of surface type and solvent type on assembled features as a function of evaporation. The final chapters of the work 5-7, focus on the virus that causes COVID-19, SARS-CoV-2. While no longer a part of an additive manufacturing process, these chapters remain a part of a collaborative effort to apply computational tools towards the experimental design process of a specific application, the development of a diagnostic or therapeutic tool. These chapters focus on the evaluation of SARS-CoV-2 spike protein, and specifically the receptor binding domain (RBD) and its interactions with the human angiotensin-converting enzyme 2 (hACE2) receptor. These structures were simulated using atomistic molecular dynamics, evaluated for the structural stability under different glycosylations that would derive from different synthesis methods for treatment (chapter 5). The interactions between the two during binding were evaluated using molecular force pulling simulations, with specific focus on analyzing the hydrogen bonding, electrostatic, and van der waals interactions between the two (chapter 6). This work demonstrated that they glycosylation contributes directly and indirectly to strengthening the interaction with hACE2. Finally the structural stability of various spike truncations synthesized in Chinese hamster ovary cells for use in therapeutic / diagnostic applications were analyzed in chapter 7.