This thesis focuses on data found in the field of computational drug discovery. New insight can be obtained by applying machine learning in various ways and in a variety of domains. Two studies... Show moreThis thesis focuses on data found in the field of computational drug discovery. New insight can be obtained by applying machine learning in various ways and in a variety of domains. Two studies delved into the application of proteochemometrics (PCM), a machine learning technique that can be used to find relations in protein-ligand bioactivity data and then predict using a virtual screen whether compounds that had never been tested on a particular protein, or set of proteins. With this, sets of compounds were suggested for experimental validation that were significant in a myriad of ways. Another study investigated the mutational patterns in cancer, applying a large dataset of mutation data and identifying several motifs in G protein-coupled receptors. The thesis also contains the work done on the Papyrus dataset, a large scale bioactivity dataset that focuses on standardising data for computational drug discovery and providing an out-of-the-box set that can be used in a variety of settings. Show less
This thesis introduces the concept of "physics-based inverse design", working on the notion that the physical driving forces governing functionality are inherently encoded in independently... Show moreThis thesis introduces the concept of "physics-based inverse design", working on the notion that the physical driving forces governing functionality are inherently encoded in independently parameterized energy functions, which can be resolved through the use of inverse design strategies.The thesis describes the development of EVO-MD, a Python-based implementation of the physics-based inverse design concept. EVO-MD is capable of automatically setting-up, performing, and analyzing molecular dynamics simulations, allowing for the evolutionary optimization of complex and dynamic features in peptides. Examples of such applications include the optimization of lipid composition and curvature sensors, and the development of peptides with antiviral properties. Show less
