Dynamics and Energy Exchange of Nonbonded Contacts within Proteins
AuthorReid, Korey Michael
AdvisorLeitner, David M
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In this work the connection between the dynamics of non-covalently bonded contacts and energy transport are investigated within the scope of proteins. Proteins have numerous contacts throughout their framework, and we start by investigating the contributions to energy transport for polar and charged contacts in the oxygen-binding protein myoglobin. We find a linear relationship between the dynamics of short-range contacts, polar contacts, and energy transport along those contacts. For charged contacts we find a diffusive relationship between contact dynamics and energy transport and key residues which have the largest energy transport among the sampled contacts. In addition, we observe anisotropic energy redistribution along contacts of myoglobin which are in good agreement with prior computational and experimental studies. We then extend this study to interglobular contacts including contacts with trapped interfacial waters for the homodimeric hemoglobin, HbI, from Scapharca Inaequivalvis. We further identify similar trends in scaling between the dynamics and energy transport as we have in myoglobin. In addition to intraglobular contacts, we present our findings on interfacial contacts between residues and trapped waters. These water-residue contacts in fact conform to both methods of analysis, the diffusive and oscillator models. We extend our analysis by computing the contributions of entropy to the free energy upon ligation for intraglobular contacts, concluding that the increase in globular entropy accounts for nearly one-fourth of the prior estimation of entropy change for the whole system upon ligation. To identify changes in communication upon ligation we present nonbonded networks constructed from the energy currents calculated for each residue pair. The changes in NBN participant residues shows the loss of communication between the hemes when ligated. Lastly, we investigate the changes to energy transport and dynamics upon mutation of a single residue of HbI. Not only are there changes to the interfacial water dynamics, as previously reported on, there are distinct changes the interfacial contact dynamics and energy transport. The most notable change is found among the deoxy T72I mutant where the oscillator model breaks down over a range of contact dynamics. We further discuss the changes in nonbonded networks upon mutation for each system compared to the wild type. Changes are found in nearly every NBN reflecting global changes in the communication network for both intra and interglobular communication.