PELE Modes

Automatically configures all simulation parameters to match the desired configuration. To choose between: induce fit, pocket exploration, binding path exploration, minimization, bias exploration, exit path

Induced fit_fast

  • induced_fit_fast: Run a short induced fit AdaptivePELE simulation paramaters by setting the center of the box in the cm of the ligand, a box radius of 10A, small rotations and translations and a high number of steric clashes and sidechain predition frequency. Useful to refine docking poses, and search new conformations within the same binding site.

induced_fit_fast: true

Induced fit_exhaustive

  • induced_fit_exhaustive: Run a long induced fit PELE simulation paramaters by setting the center of the box in the cm of the ligand, a box radius of 10A, small rotations and translations and a high number of steric clashes and sidechain predition frequency. Useful to refine docking poses, and search new conformations within the same binding site.

induced_fit_exhaustive: true

Pocket Exploration

  • ppi: Configure a global exploration by randomizing the ligand all around the protein. Then the simulation will start from all configurationsof the system at the same time. The number of configurations (ligand-protein systems) can be chosen thorugh the poses flag by default will be cpus-1. Once finished, an exhaustive induced fit exploration will follow to retrieve all best identified pockets and putative binding modes. Useful to search for putative binding modes when neither pose or pocket are known.

ppi: true

Rescoring

Simulation to refine around an initial conformation. Not looking to find a new binding mode but to minimize the actual one. Useful to minimize certain pose or to perform data augmentation for ML/DL methods

rescoring: true

Local Exploration

  • out_in: Local exploration to move the ligand from the bulk to the binding site. The box center set on the center of mass of the ligand with a radius of 30A, steering 1 50% of the times, and a slight bias towards binding energies. Useful when no docking is possible in the binding site and you need to open up the pocket.

out_in: true

Biased

  • bias: Bias exploration towards the indicated bias column. The box center is set on the center of mass of the ligand with a radius of 30A, and a bias towards the chosen metric is set. An epsilon fraction of processors are distributed proportionally to the value of a metric, and the rest are inverselyProportional distributed. Therefore, the epsilon value controls fraction of the processors that will be assigned according to the selected metric in biascolumn. Useful to speed up local explorations when the desired binding site is known

epsilon: 0.5
bias_column: 5 (starting by 1 on the reports)

Exit path

  • in_out: Explore the dissociative path of a molecule. At each step the box is center on the most exterior cluster and there is a bias towards higher values of SASA. This type accepts a exit_metric which represents a column in the report file, an exit_value which represents a value for the metric and a exit_condition parameter which can be either “<” or “>”, default value is “<”. The simulation will terminate after the metric written in the metricCol reaches a value smaller or greater than exitValue, depending on the condition specified. An example of the exit condition block that would terminate the program after 4 trajectories reaches a value of more than 0.9 for the sixth column (6th starting to count from 1) of the report file would look like below. Useful when studying the dissoative binding path, or to open up the pocket

in_out: true
exit_value: 0.9
exit_condition: ">"
exit_trajnum: 4