Limitations of Fixed-Point-Charge Force Fields for Metal Coordination Modes in Proteins: A Multilevel Study of Ca2+ in Integrin αVβ3.

Abstract

Standard biomolecular force fields often present limitations in modeling metal coordination modes. We combined classical and QM/MM molecular dynamics to investigate Ca2+-mediated binding of cRGD to integrin αVβ3. We show that different metal coordination modes imply variations in the partial charges of the metal-coordinating atoms, which, if incorporated in the force field, substantially alter the free energy landscape. These results highlight the value of QM-based multilevel approaches to accurately capture metal coordination modes in biomolecular systems.

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