Structural stability of Calmodulin-target peptide complex at different temperatures based on molecular dynamics simulation

Abstract

Calmodulin (CaM) is a multifunctional protein commonly found in various eukaryotic cells that can bind Ca²⁺, making it highly valuable for research in agriculture, medicine, the environment, and other fields. Protein functionality is intricately linked to its structure. To understand how varying temperatures affect the structural integrity of CaM protein at the molecular level, the effect of temperature on the structural stability of CaM-peptide complex was investigated based on the molecular dynamics (MD) simulation. Some analyses including the root mean square deviation (RMSD) values, interaction energies, the decomposition of total energy of the system, the binding mechanism for Ca²⁺, and the secondary structure of CaM-peptide at different temperatures have been made in this work. The RMSD increased from 0.5277 nm (298 K) to 0.6949 nm (400 K), indicating a loss of structural stability. As temperature increases, the interaction energies between CaM-peptide and Ca²⁺ exhibit a decline, and the number of oxygen atoms in the 4 Å range around the CaM-peptide ion tends to decrease, with the average value of the number of oxygen atoms in the 4 Å range of CaM-peptide decreasing from 7.48039 (298 K) to 6.36614 (400 K) with Coulombic interactions playing a pivotal role in stabilizing Ca²⁺. This decline in hydrogen bonding is directly linked to a decrease in protein stability at higher temperatures, highlighting the thermal sensitivity of the protein’s structural framework. The stable secondary structures, including the α-helix, are disrupted as temperatures increase, leading to the gradual unwinding of the α-helix and a loss of structural integrity. This work explores the molecular-level structural stability of CaM, enhancing our understanding of CaM protein and its potential applications.

Graphical Abstract