Date of Award

August 2013

Degree Type


Degree Name

Doctor of Philosophy



First Advisor

Dilano Saldin

Committee Members

Abbas Ourmazd, Valerica Raicu, Marius Schmidt, Peter Schwander


The world's first x-ray free electron laser (XFEL), the Linac Coherent Light Source (LCLS) at the Stanford Linear Accelerator Center (SLAC) is now creating X-ray pulses not only of unprecendented brilliance; (a billion times brighter than the most powerful previous sources [8]) but also of ex- tremely short duration. Amongst the promised capabilities of this fourth- generation x-ray sources is the ability to record diffraction patterns from individual bio-molecules. The very first XFEL ''diffract and destroy'' exper- iments are being performed on relatively large objects such as viruses. To quote from Caspar and Klug[2], ''there are only a limited number of efficient designs possible for biological container which can be constructed from a large number of identical protein molecules-the two basic designs are helical tubes and icosahedral shells". Viruses have regular shapes since their protein coats are formed by the self assembly of identical protein subunits which are coded by their genetic material. Here we develop a test based on the angular correlations of measured diffraction data to determine if the scattering is of an icosahedral particle. For a positive correlation test; an efficient algorithm can combine diffraction data from multiple shots of particles frozen in completely random orientations to generate a full 3-D image of the icosahedral particle. With this method it is expected to be possible to increase the concentration of particles in a solution beyond that of a single particle per snapshot thus allowing the possibility to get more signals from particles in the solvant. We sucessfully apply this method [3] to reconstruct 3-D images of satellite tobacco necrosis virus (STNV) whose atomic coordinates are given in Protein Data Bank entry 2BUK and of paramecium bursarium chlorella viruses (PBCV) from experimental data deposited at Most of prior structural studies involve scattering by ensembles of biomolecules or viruses, often in the form of crystals. However the state of biomolecules or viruses could be altered by the crystallization process. The understanding of bio-functioning of those ultrasmall quantities could be greatly enhanced if the structural studies were performed on individual uncrystallized particles. Fiber diffraction played a pioneering role for solving the structure of syn- thetic polypeptides [4], structure of deoxyribonucleic acid (DNA) [5] and the structure of helical viruses [6] to name only three of the most important. In a typical fiber diffarction experiment identical particles are all aligned along the fiber axis which give rise to layer lines. In this work we have shown that fiber diffraction can be obtained from a single particle diffraction volume reconstructed from completely randomly oriented helical structures, thus ob- viating the need of single axis alignment done experimentally such as forming lasers, laser- or flow-alignment.

Included in

Physics Commons