Flexibility of Binding Site is Essential to the Ca²⁺ Selectivity in EF-Hand Calcium-Binding Proteins.

ABSTRACT: High binding affinity and selectivity of metal ions are essential to the function of metalloproteins. Thus, understanding the factors that determine these binding characteristics is of major interest for both fundamental mechanistic investigations and guiding of the design of novel metalloproteins. In this work, we perform QM cluster model calculations and quantum mechanics/molecular mechanics (QM/MM) free energy simulations to understand the binding selectivity of Ca²⁺ and Mg²⁺ in the wild-type carp parvalbumin and its mutant. While a nonpolarizable MM model (CHARMM36) does not lead to the correct experimental trend, treatment of the metal binding site with the DFTB3 model in a QM/MM framework leads to relative binding free energies (ΔΔG_bind) compar

SUBMITTER: Lai R 

PROVIDER: S-EPMC11102802 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature