Deciphering the molecular recognition mechanism of multidrug resistance Staphylococcus aureus NorA efflux pump using a Supervised Molecular Dynamics approach.

Legend of Movie-S1

The Movie is composed by four synchronized and animated panels that show different aspects of the SuMD simulation. The time evolution is reported in nanosecond. In the first panel (upper left), the molecular representation of the system is shown. The MdfA backbone is represented by the new cartoon style (cyan). The CLM is shown in yellow and by a transparent surface. The protein residues within 3 Å from the ligand are made explicit by a stick representation.

In the second panel (upper-right), the CM-distance between the protein and the ligand centers of mass is reported.

In the third panel (lower left), the MMGBSA energy profile is reported.

In the fourth panel (lower-right) cumulative electrostatic interactions are reported for the 15 MdfA residues most contacted by CLM during the whole simulation.

Legend of Video-S2

The Movie shows the SuMD trajectory of CLM on MdfA compared to the CLM crystallographic pose. MdfA is represented in cyan new cartoon transparency. The crystallographic pose is showed in yellow while the experimental one in light green. At 16.69 ns a RMSD value of 1.77 Å is highlighted.

Legend of Video-S3

The Movie is composed by four synchronized and animated panels that show different aspects of the SuMD simulation. The time evolution is reported in nanosecond. In the first panel (upper left), the system is shown. The NorA backbone is represented by the new cartoon style (red) and the protein residues within 3 Å of CPX are showed in stick. CPX is rendered by a green stick.

In the second panel (upper-right), the distance between the centre of mass of the ligand and the protein during the trajectory is reported.

In the third panel (lower left), the MMGBSA energy profile is reported. In the fourth panel (lower-right) cumulative electrostatic interactions are reported for the 15 NorA residues most contacted by CPX during the whole SuMD trajectory.

It is important to note that the following video has a duration that is half of the simulation of SuMD. However, this straid does not alter the description of the trajectory performed by the ligand.

Legend of Video-S4

The Movie depicts the clustering analysis of CPX during the whole SuMD simulation. The NorA protein is shown in red new cartoon transparency. CPX is rendered by a light-green stick and by a transparent surface. The spheres are shown in 7 different colours, according to the different clusters. Each sphere dimension is in according to the cluster dimensions. After a first recognition site, the ligand conformations are clustered in different sites of the NorA channel. It is important to note that the following video has a duration that is half of the simulation of SuMD. However, this straid does not alter the description of the trajectory performed by the ligand.