Over 40% of eukaryotic
proteomic sequences have been predicted
to be intrinsically disordered proteins (IDPs) or intrinsically disordered
regions (IDRs) and confirmed to be associated with many diseases.
However, widely used force fields cannot well reproduce the conformers
of IDPs. Previously the <i>ff99IDPs</i> force field was
released to simulate IDPs with CMAP energy corrections for the eight
disorder-promoting residues. In order to further confirm the performance
of <i>ff99IDPs</i>, three representative IDP systems (arginine-rich
HIV-1 Rev, aspartic proteinase inhibitor IA<sub>3</sub>, and α-synuclein)
were used to test and evaluate the simulation results. The results
show that for free disordered proteins, the chemical shifts from the <i>ff99IDPs</i> simulations are in quantitative agreement with
those from reported NMR measurements and better than those from <i>ff99SBildn</i>. Thus, <i>ff99IDPs</i> can sample more
clusters of disordered conformers than <i>ff99SBildn</i>. For structural proteins, both <i>ff99IDPs</i> and <i>ff99SBildn</i> can well reproduce the conformations. In general, <i>ff99IDPs</i> can successfully be used to simulate the conformations
of IDPs and IDRs in both bound and free states. However, relative
errors could still be found at the boundaries of ordered residues
scattered in long disorder-promoting sequences. Therefore, polarizable
force fields might be one of the possible ways to further improve
the performance on IDPs
