title   
  

Driving calmodulin protein towards conformational shift by changing ionization states of selected residues

Negi, Sunita and Atılgan, Ali Rana and Atılgan, Canan (2012) Driving calmodulin protein towards conformational shift by changing ionization states of selected residues. In: IUPAP Conference on Computational Physics (CCP 2011), Gatlinburg, Tennessee (Accepted/In Press)

WarningThere is a more recent version of this item available.

[img]
Preview
PDF - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
1205Kb

Abstract

Proteins are complex systems made up of many conformational sub-states which are mainly determined by the folded structure. External factors such as solvent type, temperature, pH and ionic strength play a very important role in the conformations sampled by proteins. Here we study the conformational multiplicity of calmodulin (CaM) which is a protein that plays an important role in calcium signaling pathways in the eukaryotic cells. CaM can bind to a variety of other proteins or small organic compounds, and mediates different physiological processes by activating various enzymes. Binding of calcium ions and proteins or small organic molecules to CaM induces large conformational changes that are distinct to each interacting partner. In particular, we discuss the effect of pH variation on the conformations of CaM. By using the pKa values of the charged residues as a basis to assign protonation states, the conformational changes induced in CaM by reducing the pH are studied by molecular dynamics simulations. Our current view suggests that at high pH, barrier crossing to the compact form is prevented by repulsive electrostatic interactions between the two lobes. At reduced pH, not only is barrier crossing facilitated by protonation of residues, but also conformations which are on average more compact are attained. The latter are in accordance with the fluorescence resonance energy transfer experiment results of other workers. The key events leading to the conformational change from the open to the compact conformation are (i) formation of a salt bridge between the N-lobe and the linker, stabilizing their relative motions, (ii) bending of the C-lobe towards the N-lobe, leading to a lowering of the interaction energy between the two-lobes, (iii) formation of a hydrophobic patch between the two lobes, further stabilizing the bent conformation by reducing the entropic cost of the compact form, (iv) sharing of a Ca+2 ion between the two lobes.

Item Type:Papers in Conference Proceedings
Subjects:Q Science > QD Chemistry > QD450-801 Physical and theoretical chemistry
Q Science > QC Physics > QC1 General
ID Code:20410
Deposited By:Canan Atılgan
Deposited On:07 Dec 2012 23:33
Last Modified:09 Jan 2013 23:01

Available Versions of this Item

Repository Staff Only: item control page