"Wet" views of protein binding interfaces and hot spots

• Main Author: Li, Zhenhua.
• Other Authors: He Ying
• Format: Theses and Dissertations
• Language: English
• Published: 2013
• Subjects: DRNTU::Science::Biological sciences::Biomathematics; DRNTU::Engineering::Bioengineering
• Online Access: http://hdl.handle.net/10356/53015
• Institution: Nanyang Technological University

Protein-protein binding interfaces and hot spots are very popular topics in structural biology due to their considerable importance in protein-protein interaction. Understanding protein-protein binding interfaces and hot spots is a fundamental task for comprehending life at a molecular−or even atomic−level, and many applications, such as protein engineering and drug design, can benefit from them. However, in previous studies, protein binding interface models lack energetic relevance and protein binding hot spot models lack either interpretability or good performance. Moreover, the role of water is often underestimated, although water engages in interactions as part of the protein binding complexes, interfaces, or even hot spots. Therefore, the aim of this work is to enhance the understanding of protein-protein interactions by building better interface and hot spot models with special consideration of the water information. In this work, several protein binding interface and hot spot models have been proposed. They are the protein-water-protein interface model, geometrically centered region (GCR) and deeply buried atomic contacts (DBAC) hot spot models, and onion-like interface, a model for both protein binding interfaces and hot spots. Protein-water-protein interface, or tripartite interface, is a “wet” model where water is explicitly considered as a part of the interface. An interface is defined as a tripartite graph consisting interfacial water and atoms/residues from the partners. By using this model and burial level−a concept we have created to measure the distance of an atom/residue to bulk solvent−water distribution in protein binding interfaces is studied. Interfacial water molecules are generally distributed in a progressive “dry-core-wet-rim” topology, although with a few counterexamples.