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arXiv · 2606.28463

Limitations of Classical Force Fields for Metal Coordination Modes in Proteins: A Multilevel Study of Ca$^{2+}$ in Integrin $\alpha_V\beta_3$

Levy Andrea·Frigerio Giulia·Grollier Jules·Siani Paulo·Di Valentin Cristiana·Rothlisberger Ursula
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Abstract

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.

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Levy Andrea, Frigerio Giulia, Grollier Jules, Siani Paulo, Di Valentin Cristiana, Rothlisberger Ursula. 2026-06-26. Limitations of Classical Force Fields for Metal Coordination Modes in Proteins: A Multilevel Study of Ca$^{2+}$ in Integrin $\alpha_V\beta_3$. https://arxiv.org/abs/2606.28463

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