Seems like binding of that compounds caused higher instability of the protein complex leading to extended protein conformational fluctuations... Also implies that there is shifting of amino acid residues from the solvent accessible area in the protein during the simulation period.....

Regards

Have you checked the RMSD, RMSF, and radius of gyration to see if large-scale conformational changes or unfolding event took place somewhere in the spike?

We have checked the RMSD, RMSF and Radius of gyration. There were no large scale conformational changes but still got spikes.