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Optimization of Protein Backbone Dihedral Angles by Means of Hamiltonian Reweighting
journal contribution
posted on 2016-08-25, 00:00 authored by Christian Margreitter, Chris OostenbrinkMolecular dynamics
simulations depend critically on the accuracy
of the underlying force fields in properly representing biomolecules.
Hence, it is crucial to validate the force-field parameter sets in
this respect. In the context of the GROMOS force field, this is usually
achieved by comparing simulation data to experimental observables
for small molecules. In this study, we develop new amino acid backbone
dihedral angle potential energy parameters based on the widely used
54A7 parameter set by matching to experimental J values
and secondary structure propensity scales. In order to find the most
appropriate backbone parameters, close to 100 000 different
combinations of parameters have been screened. However, since the
sheer number of combinations considered prohibits actual molecular
dynamics simulations for each of them, we instead predicted the values
for every combination using Hamiltonian reweighting. While the original
54A7 parameter set fails to reproduce the experimental data, we are
able to provide parameters that match significantly better. However,
to ensure applicability in the context of larger peptides and full
proteins, further studies have to be undertaken.
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