1 Main Manuscript for Zn-dependent structural transition of SOD1 modulates its ability to undergo liquid-liquid phase separation. Bidisha Das a,b,# , Sumangal Roychowdhury a,# , Priyesh Mohanty c , Azamat Rizuan c , Jeetain Mittal c,* , Krishnananda Chattopadhyay a,b,* # co-first authors. [a] Structural Biology and Bioinformatics Division, CSIR- Indian Institute of Chemical Biology, Kolkata- 700 032, India. [b] Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, India. [c] Artie McFerrin Department of Chemical Engineering, Texas A&M University, College Station, TX 78743 *Jeetain Mittal, Krishnananda Chattopadhyay Email: jeetain@tamu.edu, krish@iicb.res.in Author Contributions: BD and SR carried out the experiments and analyzed the data. PM and AR performed and analyzed the simulations. KC and JM supervised the study. BD and SR wrote the initial draft of the manuscript using the inputs from all authors. KC and JM prepared the final version. All authors approved the final version of the manuscript. Competing Interest Statement: Authors declare no competing interest. Classification: Physical Sciences, Biophysics and Computational Biology. Keywords: Amyotrophic Lateral Sclerosis (ALS), SOD1, Liquid-liquid phase separation (LLPS), Aggregation, Molecular dynamics (MD) simulation. This PDF file includes: Main Text Figures 1 to 7 . CC-BY-NC 4.0 International license available under a (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made The copyright holder for this preprint this version posted February 20, 2022. ; https://doi.org/10.1101/2022.02.20.481199 doi: bioRxiv preprint