Temperature dependent conformation studies of Calmodulin Protein using Molecular Dynamics

27th IUPAP Conference on Computational Physics

物理学;计算机科学

Aneja, Sahil^1 ; Bhartiya, Vivek Kumar^2 ; Negi, Sunita^3

Cluster Innovation Centre (CIC), University of Delhi, Delhi, India^1

Centre for Photonics and Quantum Materials, Skolkovo Institute of Science and Technology, Moscow, Russia^2

Amity University, Manesar, Haryana Gurgaon, India^3

关键词: Calcium ion concentration;    Conformation change;    Fluorescence measurements;    Molecular dynamics simulations;    Physical interpretation;    Quantitative comparison;    Structural interpretation;    Temperature dependent;   

Others  :  https://iopscience.iop.org/article/10.1088/1742-6596/759/1/012022/pdf
DOI  :  10.1088/1742-6596/759/1/012022

学科分类：计算机科学（综合）

来源: IOP

【 摘 要 】

Calmodulin (CaM) protein plays a very crucial role in the calcium signaling inside the eukaryotic cell structure [1, 2]. It can also bind to other proteins/targets and facilitate various activities inside the cell [3, 4]. Temperature dependent conformation changes in the CaM protein are studied with extensive molecular dynamics simulations. The quantitative comparison of simulation data with various forms of experimental results probing different aspects of the folding process can facilitate robust assessment of the accuracy of the calculations. It can also provide a detailed structural interpretation for the experimental observations as well as physical interpretation for theory behind different aspects of the experiment. Earlier these kinds of studies have been performed experimentally using fluorescence measurements as in [5]. The calcium bound form of CaM is observed to undergo a reversible conformation change in the range 295-301 K at calcium ion concentration 150 mM. The transition temperature was observed to depend on the calcium ion concentration of the protein. Leap-dynamics approach was used earlier to study the temperature dependent conformation change of CaM [6]. At 290 K, both the N- and C-lobes were stable, at 325 K, the C-lobe unfolds whereas at 360 both the lobes unfold [6]. In this work, we perform molecular dynamics simulations of 100 ns each for the temperatures 325 K and 375 K on the apo form of CaM, 3CLN and 1CFD. A remarkable dependence of the temperature is observed on the overall dynamics of both the forms of the protein as reported in our earlier study [7, 8]. 1CFD shows a much flexible linker as compared to 3CLN whereas the overall dynamics of the lobes mainly N-lobe is observed to be more in later case. Salt bridge formation between the residues 2 (ASP) and 148 (LYS) leads to a more compact form of 1CFD at 325 K. The unfolding of the protein is observed to increase with the increase in the temperature similar to the earlier reported studies [8].