Computational Methods as Applied to Molecular Recognition in RNA.

Download or read book Computational Methods as Applied to Molecular Recognition in RNA. written by P. Therese Lang and published by . This book was released on 2006 with total page 538 pages. Available in PDF, EPUB and Kindle. Book excerpt: The aim of this thesis was to improve computational methods for structure based drug design, particularly for RNA targets. For the first portion, we present a critical evaluation of various computational drug design algorithms for their ability to predict experimental binding poses and rank libraries of small molecules against protein targets. In particular, we characterize the strengths and weaknesses of the ligand sampling method for the DOCK suite of programs. In the second portion of the thesis, we apply the lessons learned from protein targets to the disruption of protein-RNA interactions critical to the life cycle of the HIV virus. As a class, RNA historically has presented a difficult computational challenge both due to its highly localized charge and flexibility. Therefore, we have extended protocols and added new protocols in existing software packages such as DOCK and AMBER to predict experimental binding poses, once again validating our results using experimental data. Finally, we apply these protocols both to develop libraries of small molecules against druggable RNA targets and to establish a fragment-based library designed to find new scaffolds for RNA.