iGemdock 2.0 and SiMMap: Post-screening analysis for structure-based drug design

Autor: Lin, Shen-Rong, 林伸融
Rok vydání: 2014
Druh dokumentu: 學位論文 ; thesis
Popis: 102
Structure-based virtual screening is often used to find lead compounds from the hundreds of thousands of compounds. There are already many success stories using structure-based virtual screening. However, because of the incomplete understanding of ligand binding mechanisms and the subsequently imprecise scoring algorithms, How to identify the potential drug molecules of a target protein is still a big challenge. We apply two concepts from our previous works: (1) Deriving pharmacological interactions by improving the post-screening analysis module of iGEMDOCK (2) Designing the SiMMap server to construct site-moiety maps for understanding the key feature of protein-compound binding mechanisms. In order to enhance the accuracy and usefulness of virtual drug screening, based on our core technology GEMDOCK, we developed the iGEMDOCK. iGEMDOCK provides an easy-to-use graphic and integrated environment, utilizing a post-screening analysis module to mine the pharmacological interactions based on protein-compound interaction profiles and to cluster the screened compounds. Finally, iGEMDOCK ranks and visualizes the screening compounds by combining the pharmacological interactions and energy-based scoring function of GEMDOCK. To identify the key features that are essential to trigger or block the biological responses of the target proteins, we presented the SiMMap server to infer the key features by identifying the site-moiety map with anchors. Furthermore, we describe the relationship between the target protein and ligand, moiety preferences and physico-chemical properties of the binding site and pocket-moiety interaction type (E, H or V). We believe that SiMMap is able to provide biological insights for drug discovery and optimization of lead compounds.
Databáze: Networked Digital Library of Theses & Dissertations
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