Calcium Binding to Calmodulin by Molecular Dynamics with Effective Polarization.
Calcium represents a key biological signaling ion with the EF-hand loops being its most prevalent binding motif in proteins. We show using molecular dynamics simulations with umbrella sampling that including electronic polarization effects via ionic charge rescaling dramatically improves agreements with experiment in terms of the strength of calcium binding and structures of the calmodulin binding sites. The present study thus opens way to accurate calculations of interactions of calcium and other computationally difficult high-charge-density ions in biological contexts.
Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo nam. 2, 16610 Prague 6, Czech Republic.
Miriam
M
Kohagen
Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo nam. 2, 16610 Prague 6, Czech Republic.
Martin
M
Lepšík
Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo nam. 2, 16610 Prague 6, Czech Republic.
Pavel
P
Jungwirth
EF-hand motif; calcium-binding protein; charge scaling; free energy calculations; umbrella sampling