Limitations of Classical Force Fields for Metal Coordination Modes in Proteins: A Multilevel Study of Ca$^{2+}$ in Integrin $\alpha_V\beta_3$
Standard biomolecular force fields often present limitations in modeling metal coordination modes. Here, we combined classical and QM/MM molecular dynamics simulations to investigate the Ca$^{2+}$ mediated binding of cRGD to integrin $\alpha_V\beta_3$. The results demonstrate the inherent limitations of fixed-point-charge force fields in reproducing asymmetric binding modes and highlight the value of QM-based multilevel approaches to assess the correctness and accuracy of FF models and capture metal coordination modes in complex biomolecular systems.
physics.chem-ph↗