A Computational Study of Crystal Contacts
X-ray crystallography has provided remarkable perception of protein structures, revealing sharp details on atomic coordinates and flexibility. Though there are distinctions across many refinement protocols, integrated within each is a heavily weighted experimental data term. Under the assumption that the data retrieved is of high enough quality, crystallographers trust refinement techniques that depend lightly on force fields and strongly on experimental data. Certain structures are particularly challenging to solve for, as they represent dynamic, inhomogeneous systems and yield diffraction data of limited resolution. Incorporating force fields into refinement can improve the structures representing these more intricate systems. Further, if an effective force field can successfully discriminate between good and bad structures, then it can be unfailing in refinement protocols, thus beneficial for solving structures. This thesis reveals energies of crystal contacts, calculated as a means to test the ability of the force field to differentiate between high and low quality PDB structures. From the results, it is recognized that force fields can reliably assist in structure refinement. There is a clear dependence of x-ray crystal structure quality on the energy of crystal contacts. Under the influence of a force field, x-ray refinement does not have to be limited to a single molecule; the system can be extended to an assembly of asymmetric units. Such an extension can be advantageous when refining the occupancies of side chains solved at alternate conformations. Crystal contact energies have also quantitatively shown the ability force fields have for uncovering cooperativity between amino acids solved at two or more conformations. This thesis particularly emphasizes the power of the AMBER force field in evaluating the quality of crystal packing.
Skrynnikov, Purdue University.
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