Interaction
of Charged Amino-Acid Side Chains with
Ions: An Optimization Strategy for Classical Force Fields
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Abstract
Many well-established classical biomolecular
force fields, fitted
on the solvation properties of single ions, do not necessarily describe
all the details of ion pairing accurately, especially for complex
polyatomic ions. Depending on the target application, it might not
be sufficient to reproduce the thermodynamics of ion pairing, but
it may also be necessary to correctly capture structural details,
such as the coordination mode. In this work, we analyzed how classical
force fields can be optimized to yield a realistic description of
these different aspects of ion pairing. Given the prominent role of
the interactions of negatively charged amino-acid side chains and
divalent cations in many biomolecular systems, we chose calcium acetate
as a benchmark system to devise a general optimization strategy that
we applied to two popular force fields, namely, GROMOS and OPLS-AA.
Using experimental association constants and first-principles molecular
dynamics simulations as a reference, we found that small modifications
of the van der Waals ion–ion interaction parameters allow a
systematic improvement of the essential thermodynamic and structural
properties of ion pairing