Section: New Results

Generating conformational transition paths with low potential-energy barriers for proteins

Participants: Minh Khoa Nguyen, Léonard Jaillet and Stéphane Redon.

Publication: Journal of Computer-Aided Molecular Design, 2018 [66].

The knowledge of conformational transition paths in proteins can be useful for understanding protein mechanisms. Recently, we have introduced the As-Rigid-As-Possible (ARAP) interpolation method, for generating interpolation paths between two protein conformations. The method was shown to preserve well the rigidity of the initial conformation along the path. However, because the method is totally geometry-based, the generated paths may be inconsistent because the atom interactions are ignored. Therefore, we introduce a new method to generate conformational transition paths with low potential-energy barriers for proteins. The method is composed of three processing stages. First, ARAP interpolation is used for generating an initial path. Then, the path conformations are enhanced by a clash remover. Finally, Nudged Elastic Band, a path-optimization method, is used to produce a low-energy path. Large energy reductions are found in the paths obtained from the method than in those obtained from the ARAP interpolation method alone. The results also show that ARAP interpolation is a good candidate for generating an initial path because it leads to lower potential-energy paths than two other common methods for path interpolation (see Figure 1 for an example of optimized transition path).

Figure 1. The path for diphtheria toxin after ARAP interpolation and NEB optimization.