Effect of the Lys62Ala Mutation on the Thermal Stability of Bst HPr Protein by Molecular Dynamics

• Published in: International journal of molecular sciences Vol. 25; no. 12
• Main Authors: Martínez-Zacarias, Aranza C, López-Pérez, Edgar, Alas-Guardado, Salomón J
• Format: Journal Article
• Language: English
• Published: Switzerland 07.06.2024
• Subjects: Amino Acid Substitution; Bacterial Proteins - chemistry; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Hydrogen Bonding; Molecular Dynamics Simulation; Mutagenesis, Site-Directed; Mutation; Protein Conformation; Protein Stability; Temperature; molecular staple; salt bridge network; BstHPr protein; thermal stability; wild type; molecular dynamics; mutant
• ISSN: 1422-0067

We analyzed the thermal stability of the HPr protein through the site-directed point mutation Lys62 replaced by Ala residue using molecular dynamics simulations at five different temperatures: 298, 333, 362, 400, and 450 K, for periods of 1 μs and in triplicate. The results from the mutant thermophilic HPrm protein were compared with those of the wild-type thermophilic HPr protein and the mesophilic HPr protein. Structural and molecular interaction analyses show that proteins lose stability as temperature increases. Mutant and wild-type proteins behave similarly up to 362 K. However, at 400 K the mutant protein shows greater structural instability, losing more buried hydrogen bonds and exposing more of its non-polar residues to the solvent. Therefore, in this study, we confirmed that the salt bridge network of the Glu3-Lys62-Glu36 triad, made up of the Glu3-Lys62 and Glu36-Lys62 ion pairs, provides thermal stability to the thermophilic HPr protein.