Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.10.13.338046v1?rss=1 Authors: Hou, Q., Pucci, F., Ancien, F., Kwasigroch, J. M., Bourgeas, R., Rooman, M. Abstract: Motivation: Although structured proteins adopt their lowest free energy conformation in physiological conditions, the individual residues are generally not in their lowest free energy conformation. Residues that are stability weaknesses are often involved in functional regions, whereas stability strengths ensure local structural stability. The detection of strengths and weaknesses provides key information to guide protein engineering experiments aiming to modulate folding and various functional processes. Results: We developed the SWOTein predictor which identifies strong and weak residues in proteins on the basis of three types of statistical energy functions describing local interactions along the chain, hydrophobic forces and tertiary interactions. The large-scale comparison of the different types of strengths and weaknesses showed their complementarity and the enhancement of the information they provide. We applied SWOTein to apocytochrome b562 and found good agreement between predicted strengths and weaknesses and native hydrogen exchange data. Its application to an amino acid-binding protein identified the hinge at the basis of the conformational change. SWOTein is both fast and accurate and can be applied at small and large scale to analyze and modulate folding and molecular recognition processes. Availability: The SWOTein webserver provides the list of predicted strengths and weaknesses and a protein structure visualization tool that facilitates the interpretation of the predictions. It is freely available for academic use at http://babylone.ulb.ac.be/SWOTein. Copy rights belong to original authors. Visit the link for more info