Linear molecules have more conformational flexibility, therefore you will probably work with an ensemble of conformations available to the ligand for docking, or go for flexible docking, as you would for a peptide. As complex formation decreases the conformational entropy, the flexibility reduces the binding energy. Even when starting from a flexible lead compound, constraining the overall flexibility of the ligand to the actual binding conformation can improve affinity, therefore these leads are developed into more rigid cyclical compound in drug development.

Hello Satyam,

Annemarie is right! You can perform rigid molecular docking fixing some rotatable bonds to improve the binding affinity of your ligand and reduce the conformational entropy. This computational procedure allows you to analyze some regions of your molecule for further improvement, regarding the addition of double and triple bonds to reduce its flexibility.

I wish you the best!

Nonacosane type molecules have large number of confirmation which is less suitable for binding because it is against the Lipinski's rule of five.