Haifeng Chen, School of Life Sciences and Biotechnology in SJTU
520 Pao Yue-Kong Library
Intrinsically disordered proteins (IDPs) or intrinsically disordered regions have not fixed tertiary structure, but play key roles in signal regulation, molecule recognition, and drug target. However it is difficult to study the structure and function of IDPs by traditional experimental methods because of their diverse conformations. Limitations of current generic protein force fields and solvent models were reported in the previous simulations of IDPs. We have also explored to overcome these limitations by developing ff99IDPs and ff14IDPs force fields to correct the dihedral distribution for eight disordered promoting residues. Here, we extend our correction of backbone dihedral terms to all 20 naturally occurring amino acids in the residue-specific force field (ff14IDPsrs) to further improve the quality in the modeling of IDPs. Extensive tests of seven IDPs and 14 unstructured short peptides show that the simulated secondary chemical shifts with the ff14IDPsrs force field are in quantitative agreement with those from NMR experiment and are more accurate than the base generic force field and also our previous ff14IDPs that only corrects the eight disorder-promoting amino acids. The influences of solvent models were also investigated and found to be less important. Finally our explicit solvent MD simulations further show that ff14IDPsrs can still be used to model structural and dynamical properties of two tested folded proteins. These findings confirm that the newly developed residue specific force field ff14IDPsrs can improve the accuracy in modeling intrinsically disordered proteins.