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About

Hi, I’m Dylan Novack. I have recently completed my PhD in Chemistry at Temple University. My dissertation entitled Molecular Simulation of Mutation Effects on Protein Folding and Function was written on molecular simulations run on Folding@home in Dr. Vincent Voelz’s Lab . As a researcher, I am interested in using physics-based methods to investigate proteins in human disease and advance targeted molecular therapeutic design. The questions that I am interested in are:

1. How do biomolecular mechanisms relate to human disease?

2. How do mutations and/or chemical modifications affect biomolecular function?

3. Can we design better targeted molecular therapeutics?

To address these questions, I have used molecular simulations to describe folding and binding mechanisms at atomic resolution. Using the Folding@home (FAH) distributed computing platform I have generated trajectory datasets on the order of milliseconds. To analyze these large datasets, I have used Markov state models (MSMs) to build kinetic network maps of their conformational dynamics. However, even with FAH some rare events are still difficult to sample. To address this, I have used biased simulations to enhance interstate transitions and built multiensemble Markov models (MEMMs), which reconcile the biased and unbiased simulations into a Markov model. Towards therapeutic design, I have employed massively parallel alchemical free energy calculations to perform in silico site saturation mutagenesis (SSM) on designed proteins to predict beneficial mutations. My work up to this point has been focused on protein design, but I would like to expand into small molecule design as well. Additionally, I would like to integrate other tools, such as metadynamics simulation and machine learning into robust in silico therapeutic design pipelines. Other interests of mine include infectious disease, molecular psychiatry and neuroscience, and methods development.