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Full-Text Articles in Biochemistry, Biophysics, and Structural Biology
Optimization And Application Of Graph Neural Networks, Shuo Zhang
Optimization And Application Of Graph Neural Networks, Shuo Zhang
Dissertations, Theses, and Capstone Projects
Graph Neural Networks (GNNs) are widely recognized for their potential in learning from graph-structured data and solving complex problems. However, optimal performance and applicability of GNNs have been an open-ended challenge. This dissertation presents a series of substantial advances addressing this problem. First, we investigate attention-based GNNs, revealing a critical shortcoming: their ignorance of cardinality information that impacts their discriminative power. To rectify this, we propose Cardinality Preserved Attention (CPA) models that can be applied to any attention-based GNNs, which exhibit a marked improvement in performance. Next, we introduce the Directional Node Pair (DNP) descriptor and the Robust Molecular Graph …
Machine Learning And Solvation Theory For Drug Discovery, Lieyang Chen
Machine Learning And Solvation Theory For Drug Discovery, Lieyang Chen
Dissertations, Theses, and Capstone Projects
Drug discovery is a notoriously expensive and time-consuming process; hence, developing computational methods to facilitate the discovery process and lower the associated costs is a long-sought goal of computational chemists. Protein-ligand binding, which provides the physical and chemical basis for the mechanism of action of most drugs, occurs in an aqueous environment, and binding affinity is determined not only by atomic interactions between the protein and ligand but also by changes in their interactions with surrounding water molecules that occur upon binding. Thus, a quantitative understanding of the roles water molecules play in the protein-ligand binding process is an essential …
Computational Modeling Of Water And Proteins In Drug Discovery, Anthony Cruz Balberdy
Computational Modeling Of Water And Proteins In Drug Discovery, Anthony Cruz Balberdy
Dissertations, Theses, and Capstone Projects
This thesis aims to improve how structural and thermodynamic properties of water on protein surfaces can be exploited to aid early stage drug discovery and lead optimization. We first discuss our development of SSTMap, a public domain software suite that maps out the properties of water on biomolecular surfaces. We then show the utility of these maps in describing differences in binding affinities between congeneric pairs of ligands. We then discuss our use of solvation maps in the prospective discovery of novel binders to cytochrome C peroxidase. Finally, we present our creation and validation of a homology model of Interleukin-24 …