Baum, Daniel
[VerfasserIn]
;
h.c. Peter Deuflhard
[MitwirkendeR];
Joachim Selbig
[MitwirkendeR]
A Point-Based Algorithm for Multiple 3D Surface Alignment of Drug-Sized Molecules ; Ein punktbasierter Algorithmus zur Mehrfachüberlagerung dreidimensionaler Oberflächen von Wirkstoffmolekülen
Titel:
A Point-Based Algorithm for Multiple 3D Surface Alignment of Drug-Sized Molecules ; Ein punktbasierter Algorithmus zur Mehrfachüberlagerung dreidimensionaler Oberflächen von Wirkstoffmolekülen
Beteiligte:
Baum, Daniel
[VerfasserIn]
Erschienen:
Freie Universität Berlin: Refubium (FU Berlin), 2007
Anmerkungen:
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Beschreibung:
Title page, abstract, table of contents, and acknowledgments Abbreviations 1 1 Introduction 3 2 Molecular Analysis and Visualization 11 3 Molecular Similarity 31 4 Point-Based Surface Representation 53 5 Pairwise Surface Alignment 87 6 Multiple Surface Alignment 131 7 Summary and Concluding Remarks 153 Appendix A: Results of Pairwise Surface Alignment 157 Appendix B: Results of Multiple Surface Alignment 167 Bibliography 173 ; One crucial step in virtual drug design is the identification of new lead structures with respect to a pharmacological target molecule. The search for new lead structures is often done with the help of a pharmacophore, which carries the essential structural as well as physico-chemical properties that a molecule needs to have in order to bind to the target molecule. In the absence of the target molecule, such a pharmacophore can be established by comparison of a set of active compounds. In order to identify their common features, a multiple alignment of all or most of the active compounds is necessary. Moreover, since the "outer shape" of the molecules plays a major role in the interaction between drug and target, an alignment algorithm aiming at the identification of common binding properties needs to consider the molecule's "outer shape", which can be approximated by the solvent excluded surface. In this thesis, we present a new approach to molecular surface alignment based on a discrete representation of shape as well as physico-chemical properties by points distributed on the solvent excluded surface. We propose a new method to distribute points regularly on a surface w.r.t. a smoothly varying point density given on that surface. Since the point distribution algorithm is not restricted to molecular surfaces, it might also be of interest for other applications. For the computation of pairwise surface alignments, we extend an existing point matching scheme to surface points, and we develop an efficient data structure speeding up the computation by a factor of three. Moreover, we present ...