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Computer Simulation Studies of CLC Chloride Channels and Transporters

Mahankali, Uma
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1157115905

Abstract Details

2006, PhD, University of Cincinnati, Arts and Sciences : Chemistry.
In this dissertation, the CLC family of chloride channels and transporters are discussed with respect to their structure-function relationships. Here, we report the results from our computer simulation studies of the CLC proteins. We built homology models of four CLC proteins ClC-0, ClC-2, ClC-4 and ClC-5. These structures were validated and energy minimized to obtain working models for further simulations. Electrostatic calculations of the bacterial CLC homologue are presented, including the investigations on the effects of different parameters on the pKa shifts of a key glutamate residue. This residue was identified as a gate in the CLC channels and external proton-transfer residue in the CLC transporters. We found that the presence of three binding site chloride ions in the pore was required to shift the pKa of the glutamate residue up into a physiological pH range. The calculated pKa shifts were highly sensitive to the dielectric constant of the protein. Free energy barriers for the gate opening in bacterial CLC structure were estimated in protonated and unprotonated states of the side chain of the gate, Glu148. Further, the effect of chloride ions in the vicinity of the Glu148 was also examined. These computer simulations provide important tools for the ongoing studies into the structure-function relationships in CLC channels and transporters.
Dr. Thomas Beck (Advisor)
92 p.
CLC Chloride Channels; CLC transporters; Adaptive biasing force; electrostatic calculations; homology modeling; fast gating in CLC

Recommended Citations

Citations

  • Mahankali, U. (2006). Computer Simulation Studies of CLC Chloride Channels and Transporters [Doctoral dissertation, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1157115905

    APA Style (7th edition)

  • Mahankali, Uma. Computer Simulation Studies of CLC Chloride Channels and Transporters. 2006. University of Cincinnati, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1157115905.

    MLA Style (8th edition)

  • Mahankali, Uma. "Computer Simulation Studies of CLC Chloride Channels and Transporters." Doctoral dissertation, University of Cincinnati, 2006. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1157115905

    Chicago Manual of Style (17th edition)

ucin1157115905
743
© 2006, all rights reserved.
This open access ETD is published by University of Cincinnati and OhioLINK.