Proton to proteome, a multi-scale investigation of drug discovery

Chemical science spans multiple scales, from a single proton to the collection of proteins that make up a proteome. Throughout my graduate research career, I have developed statistical and machine learning models to better understand chemistry at these different scales, including predicting molecular properties of molecules in analytical and synthetic chemistry to integrating experiments with chemo-proteomic based machine models for drug design. Starting with the proteome, I will discuss repurposing compounds for mental health indications and visualizing the relationships between these disorders. Moving to the cellular level, I will introduce the use of the negative binomial distribution to find biomarkers collected using MS/MS and machine learning models (ML) used to select potent, non-toxic, small molecules for the treatment of castration--resistant prostate cancer (CRPC). For the protein scale, I will introduce CANDOCK, a docking method to rapidly and accurately dock small molecules, an algorithm which was used to create the ML model for CRPC. Next, I will showcase a deep learning model to determine small-molecule functional groups using FTIR and MS spectra. This will be followed by a similar approach used to identify if a small molecule will undergo a diagnostic reaction using mass spectrometry using a chemically interpretable graph-based machine learning method. Finally, I will examine chemistry at the proton level and how quantum mechanics combined with machine learning can be used to understand chemical reactions. I believe that chemical machine learning models have the potential to accelerate several aspects of drug discovery including discovery, process, and analytical chemistry.