Determining molecular conformation from distance or density data

The determination of molecular structures is of growing importance in modern chemistry and biology. This thesis presents two practical, systematic algorithms for two structure determination problems. Both algorithms are branch-and-bound techniques adapted to their respective domains. The first problem is the determination of structures of multimers given rigid monomer structures and (potentially ambiguous) intermolecular distance measurements. In other words, we need to find the the transformations to produce the packing interfaces. A substantial difficulty results from ambiguities in assigning intermolecular distance measurements (from NMR, for example) to particular intermolecular interfaces in the structure. We present a rapid and efficient method to simultaneously solve the packing and the assignment problems. The algorithm, AmbiPack, uses a hierarchical division of the search space and the branch-and-bound algorithm to eliminate infeasible regions of the space and focus on the remaining space. The algorithm presented is guaranteed to find all solutions to a pre-determined resolution. The second problem is building a protein model from the initial three dimensional electron density distribution (density map) from X-ray crystallography. This problem is computationally challenging because proteins are extremely flexible.

Department dc:contributor.department

Massachusetts Institute of Technology. Dept. of Electrical Engineering and Computer Science.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2000

Author dc:creator

• Wang, Cheuk-san, 1971-

Advisor dc:contributor.advisor

• Tomás Lozano-Pérez.

• Electrical Engineering and Computer Science.

Statement dc:rights

• M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission.

Licence dc:rights.uri

• http://theses.mit.edu/Dienst/UI/2.0/Describe/0018.mit.etheses%2f2000-2
• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/1721.1/16736

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/16736