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Intrinsically disordered protein‐specific force field CHARMM 36 IDPSFF

2018; Wiley; Volume: 92; Issue: 4 Linguagem: Inglês

10.1111/cbdd.13342

1747-0285

Hao Liu, Song Dong, Hui Lü, Ray Luo, Haifeng Chen,

Enzyme Structure and Function

Intrinsically disordered proteins ( IDP s) are closely related to various human diseases. Because IDP s lack certain tertiary structure, it is difficult to use X‐ray and NMR methods to measure their structures. Therefore, molecular dynamics simulation is a useful tool to study the conformer distribution of IDP s. However, most generic protein force fields were found to be insufficient in simulations of IDP s. Here, we report our development for the CHARMM community. Our residue‐specific IDP force field ( CHARMM 36 IDPSFF ) was developed based on the base generic force field with CMAP corrections for all 20 naturally occurring amino acids. Multiple tests show that the simulated chemical shifts with the newly developed force field are in quantitative agreement with NMR experiment and are more accurate than the base generic force field. Comparison of J‐couplings with previous work shows that CHARMM 36 IDPSFF and its corresponding base generic force field have their own advantages. In addition, CHARMM 36 IDPSFF simulations also agree with experiment for SAXS profiles and radii of gyration of IDP s. Detailed analysis shows that CHARMM 36 IDPSFF can sample more diverse and disordered conformers. These findings confirm that the newly developed force field can improve the balance of accuracy and efficiency for the conformer sampling of IDP s.