Date of Award


Degree Type


Degree Name

Doctor of Philosophy in Applied Mathematical Sciences


Applied Mathematics



First Advisor

Yana K. Reshetnyak


Study and modeling of protein structures provides an opportunity to elucidate the molecular mechanisms of key biological processes, as well as interpret experi- mental data obtained by variety of physical methods. The main goal of my work was to develop computational algorithms for the analysis of protein structures, the docking of protein-protein interactions, the implementation of these algorithms and the correlation of protein structure analysis with the results of steady-state and kinetics fluorescence measurements.

First, we developed and implemented algorithms for the decomposition of multi- component protein fluorescence spectra and the correlation of these spectral parameters with protein structural properties. The implementation is avail- able as on-line toolkit PFAST (Protein Fluorescence And Structural Toolkit) at The results of our work would allow researchers to ex- tract important novel information about protein structure and dynamics, which is probed by steady-state fluorescence spectroscopy.

Next, we developed and implemented a mathematical model to analyze the kinetic fluorescence data, which reflects the interaction of myosin subfragment 1 with one and two monomers of F-actin. Myosin and actin are the major proteins of muscles and acto-myosin interaction is responsible for the force generation in biological systems. By fitting experimental spectral data we have shown that the sequential binding of the myosin head initially with one actin monomer and then with the second actin monomer in F-actin can play a key role in force generation by actin- myosin and their directed movement.

Finally, we performed computational rigid body docking of the atomic structures of S1 and F-actin with two fixed points corresponding to the crosslinking sites and two distinct conformations of S1 on the F-actin surface. The minimization of the binding free energy of the generated complexes was done using an empiri- cal method developed previously, and it allowed us to select the best actomyosin models: where the myosin neck was pointed toward the barbed (model A) or the pointed (model B) ends of F-actin. The complex of model B was twice less stable than the complex of model A, which led to the conclusion that the second actin, with which S1 interacts, is located in the same strand, closer to the barbed end of F-actin. We concluded that, the formation of the actomyosin complex proceeds in ordered sequence: i) S1 initially binds to one actin; ii) rotates toward the barbed end of F-actin and binds with the second actin. The sequential mechanism of formation of actomyosin interface starting from one end and developing towards the barbed end could play an important role in force generation and directional movement in actin-myosin system.



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