Many pairwise additive force fields parameterized to reproduce folded protein structures are in active use for intrinsically disordered proteins (IDPs) and regions (IDRs), most of which are found to disagree with solution experiments for the disordered states. Recent modifications of protein-water and water-water energetic interactions in these standard force fields have sought to increase agreement with solution experiments of IDPsand IDRswhile also maintaining the ability to describe folded protein structures. Many-body potentials that include polarization should provide a better physical model for capturing proteins with and without intrinsic disorder, but in this case testing has been more limited for proteins of either class . We have evaluated representative non-polarizable and polarizable protein and water force fields against experimental data on the histatin 5 intrinsically disordered protein, the disorder-to-order temperature transitionfor the (AAQAA)3 repeat peptide, the TSR4 domain of F-spondin which has both folded and intrinsically disordered regions, and seven globular folded proteins ranging in size from 130-266 amino acids. We find that force fields with the largest statistical fluctuations consistent with the radius of gyration and universal Lindemann values for folded states are simultaneously valuable for describing IDPs and IDRs and disorder to order transitions. Hence the crux of what a force field should exhibit to well describe IDRs/IDPs is not just the balance between protein and water energetics, but the balance between energetic effects and configurational entropy of folded states of globular proteins.
Many pairwise additive force fields are in active use for intrinsically disordered proteins (IDPs) and regions (IDRs), some of which modify energetic terms to improve description of IDPs/IDRs, but are largely in disagreement with solution experiments for the disordered states . We have evaluated representative pairwise and many-body protein and water force fields against experimental data on representative IDPs and IDRs, a peptide that undergoes a disorder-to-order transition, and for seven globular proteins ranging in size from 130-266 amino acids. We find that force fields with the largest statistical fluctuations consistent with the radius of gyration and universal Lindemann values for folded states simultaneously better describe IDPs and IDRs and disorder to order transitions. Hence the crux of what a force field should exhibit to well describe IDRs/IDPs is not just the balance between protein and water energetics, but the balance between energetic effects and configurational entropy of folded states of globular proteins.
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parameterized to reproduce folded protein structures
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most of which are found to disagree with solution experiments for the disordered states. Recent modifications of protein-water and water-water energetic interactions in these standard force fields have sought to increase agreement with solution experiments of IDPsand IDRswhile also maintaining the ability to describe folded protein structures. Many-body potentials that include polarization should provide a better physical model for capturing proteins with and without intrinsic disorder, but in this case testing has been more limited for proteins of either class
some of which modify energetic terms to improve description of IDPs/IDRs, but are largely in disagreement with solution experiments for the disordered states
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non-polarizable and polarizable
pairwise and many-body
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the histatin 5 intrinsically disordered protein, the
representative IDPs and IDRs, a peptide that undergoes a
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temperature transitionfor the (AAQAA)3 repeat peptide, the TSR4 domain of F-spondin which has both folded and intrinsically disordered regions, and seven globular folded
transition, and for seven globular
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are simultaneously valuable for describing
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