The time profiles of the number of folded replicas in the REMD simulations for all the five training proteins. We defined the trajectory as folded if the backbone RMSD . The number of folded replicas decreases rapidly and then eventually begins to fluctuate from a certain point, i.e., for gb1, for Trp cage, for 1FSD, for 1PSV, and for BBA5, indicating each simulation has reached a steady state distribution.
(a) The 2D free energy surface of gb1 at and the corresponding averaged structure in the lowest free energy basin, , with hydrophobic core side chains. The local minimum region at corresponds to the original NMR structure. The line interval in the contour map is . (b) The simulated average pair distances of gb1 compared with NMR assignments of a total of 35 NOE proton pairs at . Three gray horizontal lines at 3.0, 4.0, and represent the upper bounds for observing strong (s), medium (m), and weak (w)/very weak (vw) NOE signals, respectively. The error bars correspond to the standard deviation of : (1) E42 (w); (2) T44 (w); (3) Y45 (w); (4) D46 (w); (5) D47 (m); (6) A48 (m); (7) T49 (m); (8) K50 (m); (9) T55 (w); (10) E56 (w); (11) G41–NH E42 (m); (12) E42–NH W43 (s); (13) T44–NH Y45 (m); (14) Y45–NH Y46 (s); (15) D46–NH D47 (s); (16) D47–NH A48 (m); (17) A48–NH T49 (m); (18) T49–NH K50 (m); (19) T51–NH F52 (m); (20) T53–NH V54 (s); (21) V54–NH T55 (s); (22) T55–NH E56 (s); (23) NH Y45–NH D46 (vw); (24) NH D46–NH D47 (vw); (25) NH D47–NH A48 (m); (26) NH A48–NH T49 (m); (27) NH T49–NH K50 (m); (28) NH K50–NH T51 (w); (29) NH T55–NH E56 (vw); (30) F52 (vw); (31) V54 (vw); (32) K50–3H Y45 (vw); (33) Y45–2H F52 (vw); (34) Y45–5H F52 (vw); (35) W43–4H F52 (vw).
The 2D free energy surface of Trp cage [(a) and (b)] at , 1FSD (c) at , 1PSV (d) at , and BBA5 (e) at . The RMSD value is calculated with the backbone atoms in residue 3–18 (assigned by NMR) for Trp cage and residues 1–21 for BBA5. For both 1FSD and 1PSV, the backbone atoms in residues 3–26 were used for the RMSD calculation. The inset image of each map is an averaged structure in the lowest free energy basin with the hydrophobic core residue side chains: Trp cage (Tyr3, Trp6, Leu7, Pro12, Pro17, Pro18, and Pro19), 1FSD and 1PSV (Ala5, Ile7, Phe12, Leu18, Phe21, Leu22, and Phe25), and BBA5 (Tyr1, Val3, Tyr6, Phe8, Leu14, Leu17, and Leu18). The line interval in all the contour maps is .
Superimposed images of the lowest free energy predicted structure (deep gray) with NMR native structure (light gray). The lowest free energy state is located at for gb1 at , for Trp cage (1L2Y) at for 1FSD, for 1PSV, and for BBA5 (1T8J) at . The side chains of the hydrophobic core residues are shown with stick. The figures were created with the PYMOL software (Ref. 44).
Experimental (CD) and simulated melting curves of gb1 (a), Trp cage (b), 1FSD (c), 1PSV (d), and BBA5 (e). The error bar is estimated by the standard error of a block average ( block) data with a 95% confidence.
Amino-acid sequences of the training set employed in this work.
The protein backbone and angle parameters in PARAM99MOD5.
The modified GB intrinsic radii employed in this study.
The selected temperatures in the REMD simulations on all the training proteins.
Thermodynamic parameters of the training set compared with experimental data and other MD simulation results. Herein the simulated values obtained with a RMSD criterion of were used for producing thermodynamic quantities. The values in parentheses were obtained by refits with Eq. (8), using the published data set of vs in each reference.
The folding criterion (RMSD) dependence of the melting temperatures for the five training species.
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