Dear Ramkumar Katturajan , in order to perform a MLSD study follow the steps below:

1. prepare the inhibitor molecules separately using Autodock tools (ADT) and save them with appropriate torsions and charges as .PDBQT files.

2. Mean while prepare the protein molecule and save as (.dpf) With individual dock parameter files of the inhibitor molecules,

3. merge the substrate’s dpf into one single file to run MLSD simulation.

4. Once ready with the merged dock parameter file, docking starts with the random initialization of the population.

MLSD stands separate from single ligand docking where different conformations of multiple ligands can be run simultaneously. To achieve this, the program loads the .PDBQT files of both substrate as well as inhibitor to perform simulation.

Dear Dr. Hicham Mechqoq Thank you very much for your suggestion.

Could you please rectify the step 3 & 4

Step 3: How can I merge dpf file? could you please provide any example if possible

Step 4: "random initialization of the population" a Lamarckian GA?

My pleasure dear Ramkumar Katturajan , concerning the points you asked for:

• Step 3: I merge them with Autodock, check this video: https://www.youtube.com/watch?v=s2nkYwUQb8s
• Step 4: I use the EDGA method based on the Lamarckian genetic algorithm, it's more precise than the traditional methods, for more details check this reference [Guan, B., Zhang, C., & Ning, J. (2016). EDGA: a population evolution direction-guided genetic algorithm for protein–ligand docking. Journal of Computational Biology, 23(7), 585-596].

best regards

Ramkumar Katturajan Hicham Mechqoq sir will you please tell me how to do merging of files

With individual dock parameter files of the inhibitor molecules, substrate’s dpf was merged into one single file to run MLSD simulation??