title: ff14IDPs force field improving the conformation sampling of intrinsically disordered proteins.
abstract: Intrinsically disordered proteins are proteins which lack of specific tertiary structure and unable to fold spontaneously without the partner binding. These intrinsically disordered proteins are found to associate with various diseases, such as diabetes, cancer, and neurodegenerative diseases. However, current widely used force fields, such as ff99SB, ff14SB, OPLS/AA, and Charmm27, are insufficient in sampling the conformational characters of intrinsically disordered proteins. In this study, the CMAP method was used to correct the φ/ψ distributions of disorder-promoting amino acids. The simulation results show that the force filed parameters (ff14IDPs) can improve the φ/ψ distributions of the disorder-promoting amino acids, with RMSD less than 0.10% relative to the benchmark data of intrinsically disordered proteins. Further test suggests that the calculated secondary chemical shifts under ff14IDPs are in quantitative agreement with the data of NMR experiment for five tested systems. In addition, the simulation results show that ff14IDPs can still be used to model structural proteins, such as tested lysozyme and ubiquitin, with better performance in coil regions than the original general Amber force field ff14SB. These findings confirm that the newly developed Amber ff14IDPs is a robust model for improving the conformation sampling of intrinsically disordered proteins.
authors.affiliation: State Key Laboratory of Microbial Metabolism, Department of Bioinformatics and Biostatistics, College of Life Sciences and Biotechnology, Shanghai Jiaotong University, Shanghai, 200240, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Song
authors.affiliation: State Key Laboratory of Microbial Metabolism, Department of Bioinformatics and Biostatistics, College of Life Sciences and Biotechnology, Shanghai Jiaotong University, Shanghai, 200240, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Microbial Metabolism, Department of Bioinformatics and Biostatistics, College of Life Sciences and Biotechnology, Shanghai Jiaotong University, Shanghai, 200240, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Ye
authors.affiliation: State Key Laboratory of Microbial Metabolism, Department of Bioinformatics and Biostatistics, College of Life Sciences and Biotechnology, Shanghai Jiaotong University, Shanghai, 200240, China.
authors.forename: Dingjue
authors.initials: D
authors.lastname: Ji
authors.affiliation: Departments of Molecular Biology and Biochemistry, Chemical Engineering and Materials Science, and Biomedical Engineering, University of California, Irvine, CA, 92697-3900, USA.
authors.forename: Ray
authors.initials: R
authors.lastname: Luo
authors.affiliation: State Key Laboratory of Microbial Metabolism, Department of Bioinformatics and Biostatistics, College of Life Sciences and Biotechnology, Shanghai Jiaotong University, Shanghai, 200240, China.|Shanghai Center for Bioinformation Technology, Shanghai, 200235, China.
authors.forename: Hai-Feng
authors.initials: HF
authors.lastname: Chen
mesh_terms: D064267:Intrinsically Disordered Proteins / Q000737:chemistry*; D011487:Protein Conformation
chemical_list: D064267:Intrinsically Disordered Proteins
keywords: CMAP correction; IDPs; ff14IDPs; force field