f6-ijms-10-01121: Distribution of the total potential energy of all sampled conformations from the BP-Rex MD simulation (continuous line) and T-Rex MD simulation (dashed line).

Mentions: Although the projection of sampled states on PCs and various coordinates relevant for protein folding can give interesting hints on which physical and structural features are changing during structure formation the plots do not reveal information on the energetic driving forces for folding. To compare the sampling efficiency of BP-Rex MD and T-Rex MD simulation in terms of sampled potential energies the energy distribution was analyzed (Figure 6). Both simulations overall sample very similar total potential energies (distribution in Figure 6 includes all folded and unfolded structures sample during the entire simulations at the reference replica).

Kannan S, Zacharias M - Int J Mol Sci (2009)

Bottom Line: In contrast, to T-RexMD involving 16 replicas the BP-RexMD method achieved very similar sampling results with only five replicas.The result indicates that the BP-RexMD method is well suited to study folding processes of proteins at a significantly smaller computational cost, compared to T-RexMD.The analysis of the sampled potential energy contributions indicated that Trp-cage folding is favored by both van der Waals and to a lesser degree electrostatic contributions.

Affiliation: Jacobs University Bremen, Germany.

Abstract: The folding process of the 20 residue Trp-cage mini-protein was investigated using standard temperature replica exchange molecular dynamics (T-RexMD) simulation and a biasing potential RexMD (BP-RexMD) method. In contrast to several conventional molecular dynamics simulations, both RexMD methods sampled conformations close to the native structure after 10-20 ns simulation time as the dominant conformational states. In contrast, to T-RexMD involving 16 replicas the BP-RexMD method achieved very similar sampling results with only five replicas. The result indicates that the BP-RexMD method is well suited to study folding processes of proteins at a significantly smaller computational cost, compared to T-RexMD. Both RexMD methods sampled not only similar final states but also agreed on the sampling of intermediate conformations during Trp-cage folding. The analysis of the sampled potential energy contributions indicated that Trp-cage folding is favored by both van der Waals and to a lesser degree electrostatic contributions. Folding does not introduce any significant sterical strain as reflected by similar energy distributions of bonded energy terms (bond length, bond angle and dihedral angle) of folded and unfolded Trp-cage structures.