Discrete Molecular Dynamics Simulation of Biomolecules - Computational Modeling of Biological Systems - page 70

Fig. 8 De novo protein-protein interface design using DMD and Rosetta. ( a ) Starting from the
initial structure ( blue ), the DMD assisted design has significant backbone movement in both
the scaffold ( green )andtarget( magenta ) proteins. ( b ) The experimental binding assay of the
protein-protein complex redesigned using DMD-Rosetta. The redesigned scaffold protein has a
binding affinity of 100 M with the wild-type target protein. No binding is found in the control

experiment with PAK1 mutant L470E, indicating that the actual binding interface is the same as
predicted

biological macromolecules. With the continuous development of the methodology,
including the parallelization of simulation approaches [ 47 , 48 ], in the future the
DMD engine will be extended to sample the dynamics of ever larger molecules and
molecular complexes with even longer time scales. With its ability to efficiently