search algorithm with a focus on energy optimization. Confort incorporates a distance geometry approach to generate low-energy conformations, while MED-3DMC utilizes a Monte Carlo-based method. Multiconf-DOCK utilizes a systematic search approach for exploring ligand flexibility within the DOCK5 program. It extends multiple anchor segments stepwise and generates conformations by systematically rotating single, nonterminal, acyclic bonds at specified increments, while CONFECT employs an evolutionary algorithm. BRIKARD utilizes a knowledge-based approach, and ForceGen incorporates force field-based methods. TCG utilizes a systematic torsion angle search algorithm and Cxcalc utilizes a fragment fusion method and the Dreiding force field for the calculation and optimization of conformers. These tools aid in the exploration of potential binding modes and interactions. Finally, it's important to note that all of these methods generate conformations in the gas-phase and not solution or in the crystalline phase.