Faculty Advisor
Jaroslava Miksovska
Author Biographical Statement
Sebastian Scavuzzo is a fourth-year biochemistry major. Although he studies biochemistry as an undergraduate student, his research is focused primarily on computational and experimental biophysics to understand the complexity and unique nature of vital neuronal proteins. Through this research discipline, he found his passion to further his studies in protein design and small molecule docking and synthesis once he graduates in the effort of advancing pharmaceutical research.
Abstract
Proteins are important macromolecules responsible for a variety of processes in living organisms. One of the most important features of proteins is their ability to respond to environmental stimuli, such as changes in intracellular metal concentration by binding metal ions, which in turns triggers structural changes within the protein that can modify its function or allow the protein to participate in a signaling pathway. One such signaling protein is the so-called neuronal calcium sensor 1 protein or NCS1, which binds Ca2+ along with other abiogenic metals such as Li+, and the metal binding regulates NCS1 interactions with other intracellular partners. NCS1 binds Ca2+ ions through the EF-hands, consisting of a helix-loop-helix motif. The exact nature of the structural changes triggered by Ca2+ binding to the EF-hands in NCS1 is currently unknown. In an attempt to elucidate the nature of these structural changes, we performed a variety of molecular dynamics simulations on NCS1 in the calcium bound, lithium bound, and metal unbound states. We then calculated the angles between helices in EF-hands to determine if these angles change upon metal ion binding. Using the outputs of the molecular dynamics simulations, we developed a python script in house using MDAnalysis and Numpy libraries to select and calculate the angle between each alpha helix pair as a function of simulation time. Based on our calculations, the EF-hand interhelical angles change significantly upon metal binding and are even sensitive to the specific identity of the metal ion. This method of interhelical angle calculation can serve as an important tool for determining the nature of structural changes caused by the binding of ligand molecules to sensor proteins.
DOI
10.25148/FIUURJ.3.1.16
Recommended Citation
Scavuzzo, Sebastian; Cedeño, Jonathan; and Miksovska, Jaroslava
(2025)
"In Silico Calculation of Interhelical Angles in NCS1,"
FIU Undergraduate Research Journal: Vol. 3:
Iss.
1, Article 16.
DOI: 10.25148/FIUURJ.3.1.16
Available at:
https://digitalcommons.fiu.edu/undergraduate-journal/vol3/iss1/16
