Calibrated Langevin-dynamics simulations of intrinsically disordered proteins.
We perform extensive coarse-grained (CG) Langevin dynamics simulations of intrinsically disordered proteins (IDPs), which possess fluctuating conformational statistics between that for excluded volume random walks and collapsed globules. Our CG model includes repulsive steric, attractive hydrophobic, and electrostatic interactions between residues and is calibrated to a large collection of single-molecule fluorescence resonance energy transfer data on the interresidue separations for 36 pairs of residues in five IDPs: α-, β-, and γ-synuclein, the microtubule-associated protein τ, and prothymosin α. We find that our CG model is able to recapitulate the average interresidue separations regardless of the choice of the hydrophobicity scale, which shows that our calibrated model can robustly capture the conformational dynamics of IDPs. We then employ our model to study the scaling of the radius of gyration with chemical distance in 11 known IDPs. We identify a strong correlation between the distance to the dividing line between folded proteins and IDPs in the mean charge and hydrophobicity space and the scaling exponent of the radius of gyration with chemical distance along the protein.
Department of Physics, Yale University, New Haven, Connecticut 06520-8120, USA and Integrated Graduate Program in Physical and Engineering Biology, Yale University, New Haven, Connecticut 06520-8114, USA.
W Wendell
WW
Smith
Department of Physics, Yale University, New Haven, Connecticut 06520-8120, USA.
Po-Yi
PY
Ho
Department of Physics, Yale University, New Haven, Connecticut 06520-8120, USA and Integrated Graduate Program in Physical and Engineering Biology, Yale University, New Haven, Connecticut 06520-8114, USA and Department of Mechanical Engineering and Materials Science, Yale University, New Haven, Connecticut 06520-8286, USA and Department of Applied Physics, Yale University, New Haven, Connecticut 06520-8267, USA and Program in Computational Biology and Bioinformatics, Yale University, New Haven, Connecticut 06520, USA.
Corey S
CS
O'Hern
D002138:Calibration; D003198:Computer Simulation; D031541:Fluorescence Resonance Energy Transfer; D057927:Hydrophobic and Hydrophilic Interactions; D064267:Intrinsically Disordered Proteins / Q000737:chemistry*; D008958:Models, Molecular; D011487:Protein Conformation; D055672:Static Electricity
D064267:Intrinsically Disordered Proteins