DOI: 10.1021/acs.jctc.6c01320 ISSN: 1549-9618
Limitations of Fixed-Point-Charge Force Fields for Metal Coordination Modes in Proteins: A Multilevel Study of Ca2+ in Integrin αVβ3
Andrea Levy, Giulia Frigerio, Jules Grollier, Paulo Siani, Cristiana Di Valentin, Ursula RothlisbergerAbstract
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.