Date of Award
Doctor of Philosophy
Biochemistry, Biophysics and Molecular Biology
Robert L. Jernigan
This dissertation presents a new scheme to derive four-body contact potentials as a way to consider protein interactions in a more cooperative model. These new four-body contact potentials, noted as SET1 four-body contact potentials (sequential information included), show important gains in threading. SET2 four-body contact potentials (non-sequential information included) have also been developed to supplement SET1 by including spatial information. In addition to SET1 and SET2, we also include the short-range conformational energies introduced by us previously in threading. The combination of these different potentials shows significant improvement in threading tests of some decoy sets.
Protein packing is an important aspect of computational structural biology. Icosahedron is chosen as an ideal model to fit the protein packing clusters from a set of protein structures. A theoretical description of packing patterns and packing regularities of icosahedron has been proposed. We find that the order parameter (orientation function) measuring the angular overlap of directions in coordination clusters with directions of the icosahedron is 0.91, which is a significant improvement in comparison with the value 0.82 for the order parameter with the face-centered cubic (fcc) lattice. Close packing tendencies and patterns of residue packing in proteins is considered in detail and a theoretical description of these packing regularities is proposed.
Protein motion is another important field. The elastic network interpolation (ENI) model has been used to generate conformational transition intermediates of adenylate kinase (AK) based only C alpha atoms. We construct the atomistic intermediates by grafting all the other atoms except C alpha from the open form AK and then performing CHARMM energy minimization to remove steric conflicts and optimize the intermediate structures. We compare the free energy profiles for all intermediates from both CHARMM force field and statistical energy functions. And we find CHARMM total free energies can successfully captures the two energy minima representing the open form AK and the closed form AK, however the free energies from statistical energy functions can detect the energy minimum representing the semi-closed intermediate with LID domain closed and NMP domain open and the local energy minimum representing the closed form AK.
Feng, Yaping, "New statistical potentials for improved protein structure prediction" (2008). Graduate Theses and Dissertations. 10682.