Advanced optimization and sampling techniques for biomolecules using a polarizable force field

Abstract

with science and the Ph.D. process. Prof. Schnieders and the rest of the Schnieders lab provided endless support and guidance. Without his assistance, this work would not have been possible. Mallory Tollefson in particular is co-first-author on the material presented in Chapter 2, having performed most of the data collection and determined appropriate cutoff schemes. Andrew Thiel assisted in preparing the manuscript referenced in Chapter 3. Hernan Bernabe is leading the Monte Carlo Orthogonal Space Random Walk project discussed in Section 4D. Guowei Qi produced an automated script for the work described by Chapter 2, vastly reducing the human effort required and speeding up that project by months. Maya Benowitz assisted with deriving the total number of energy evaluations needed for the many-body expansion (Chapter 2). I would also like to thank the labs of Prof. Pengyu Ren, Prof. Richard Smith, Prof. Ernesto Fuentes, and Prof. Simonson. Professor Pengyu Ren and his student, Zhifeng Jing, provided data used in Chapter 3 prior to their publication, which helped us perform our study on simultaneous bookending. Prof. Richard Smith and the other members of Audiogene provided data, motivation, and critical analysis for the work in Chapter 2, which is our most directly clinically motivated work. The labs of Prof. Fuentes and Simonson assisted in the simultaneous bookending project; while we were unable to produce high-quality results on the PDZ domains iii they study, their advice and assistance was key to developing the algorithm. In addition, the Simonson lab described the native environment approximation used by the optimization work.