Assalam O alaikum

Farjana Akter

Behind SASA increasing, some factors like, temperature raise during the simulation, most of amino acids of protein hydrophobic etc.

https://dx.doi.org/10.3389%2Ffmolb.2020.00051

Hello Farjana Akter

It's sometimes obvious that the fluctuation occurs so often and abruptly; despite having the same characteristics, several peptides behave differently and lose their consensus score, and perform sudden fluctuation all of a sudden. However, these articles may help you regarding this confusion.....

Article Conformation Analysis of T1 Lipase on Alcohols Solvent using...

https://www.pnas.org/content/117/12/6430

Article Fluctuation relations in simple examples of non-equilibrium ...

Article Structure-based identification of potential SARS-CoV-2 main ...

Article Fluctuation-response inequality out of equilibrium

Best regards

Dear Farjana,

I think the explanation for your observation is quite straightforward.

Assuming, that the surface area is calculated for the whole complex (protein together with ligand), the high molecular weight (= relatively large) ligands simply increase the overall SASA, whereas the small ligand does not contribute much additional surface compared to the apo protein.

If SASA is calculated only for the protein itself, the increased surface area in the HMW complexes could be caused by an opening of the protein structure, forming a binding pocket for the larger ligands. If the surface area is then calculated only for the protein, is will be larger due to newly "solvent"-exposed residues.

I hope that helps!

Best regards

Johann