Figure 1.
Mapping of CG site types for the amino acids.
The backbone is represented by a single site at the alpha carbon (green). Sidechain sites are assigned to the mass centers of polar (light blue), apolar (gray), positive (blue) and negative (red) functional groups consisting of two or three heavy atoms. CG sites are connected by bonded interactions (red lines).
Figure 2.
Pairwise interaction potential between nonbonded backbone alpha carbons generated from atomistic force matching.
Unfolding (498 K) simulations of Trpzip (red), Leu15 (green) and Ala15 (blue) as well as 300 K MD of Ala15 (pink) yield attractive potentials that share a minimum at ∼0.6 nm. Inset (same xy scale): Correspondence in the interaction potentials between apolar sidechain sites for Trpzip (red) and a dipeptide solution of the 20 amino acids (black).
Table 1.
Peptide systems employed in all-atom reference simulations.
Table 2.
Location and depth of attractive minima in nonbonded interactions between CG site types.
Figure 3.
Temperature correspondence in CG-MD simulations of polyalanine aggregation.
The RDF between nonbonded alpha carbons is shown for CG simulations at 300 K (black dash), 498 K (pink), 600 K (blue) and 700 K (cyan) and atomistic simulations at 300 K (solid black) and 498 K (red).
Figure 4.
Heat capacity as a function of temperature for CG-REMD folding simulations of Trpzip (A), Trp-cage (B) and AdK (C).
The reference temperature for the CG model is taken to be the folding transition temperature observed for Trpzip (), defined by the maximum in Cv(T). Line and data point thickness denote error.
Figure 5.
CG-REMD folding landscapes collected at 0.6 .
The Cα RMSD from the native state is shown versus composite simulation time (A–C) or potential energy (D–F) for independent simulations (different colors) of Trpzip (A,D), Trp-cage (B,E) and AdK (C,F). Simulations were started from extended and native structures as well as their common final configuration in the case of Trp-cage. AdK simulations were started from extended, closed, open and a mixture of open and extended states; RMSD is computed from the closed crystal structure. Large structural changes between snapshots, such as folded to misfolded transitions, correspond to conformational exchanges between replicas of similar energy.
Figure 6.
The instantaneous Cα RMSD from the native state is shown for simulations starting from the native structure for Trpzip (A) and Trp-cage (B). By comparison, all-atom MD of Trpzip at 300 K yielded a mean Cα RMSD of 0.8±0.2 Å.
Figure 7.
Backbone Cα-trace structures at the end of native state CG-MD at 0.6 for Trpzip (A), Trp-cage (B) and AdK (C).
Starting native structures are shown in cyan for Trpzip/Trp-cage and as a ribbon diagram for closed AdK. Tryptophan and proline sidechains are shown in blue (A,B). The LID/NMP domains of the AdK endpoint conformations are colored green/pink for simulations starting from open AdK and orange/blue for simulations starting from closed AdK.
Figure 8.
Native state CG-MD at 0.6 starting from the open (A) and closed (B) forms of AdK.
The instantaneous Cα RMSD from the starting structure is shown for the CORE (dark gray), LID (light gray) and NMP (black) domains.
Figure 9.
Conformational transition in AdK expressed as the difference in RMSD from the open and closed states.
Simulations starting from the open structure (black circles), ΔDRMSD = −7 Å, are seen to partly converge toward simulations starting from the closed structure (gray trace), ΔDRMSD = +7 Å.
Table 3.
Distributions of radius of gyration in folding simulations.
Table 4.
Distributions of sidechain RMSD in native state simulations at 0.6 .