Abstract
Simulating protein structure flexibility using classical methods is computationally demanding, especially for large proteins. To address this challenge, we have been developing the CABS-flex method, which enables fast simulations of protein structural flexibility by combining a coarse-grained simulation approach with all-atom detail. Previously available as the CABS-flex 2.0 web server, the method has now undergone a major upgrade with the release of CABS-flex 3.0. Key improvements include the introduction of intuitive flexibility modes that simplify the control of distance restraints and allow users to reflect known or expected dynamic regions; improved all-atom reconstruction for higher-quality model generation; a new feature for de novo peptide structure prediction, supporting both linear and cyclic peptides along with their conformational flexibility; and new tools for result analysis and visualization, facilitating deeper insights into structural flexibility. Additionally, AlphaFold pLDDT-derived restraints can be used as optional input for guiding simulations. The method accepts input as either a PDB/mmCIF structure or a sequence (for peptide modeling). Advanced options allow users to incorporate experimental or computational restraints. The CABS-flex 3.0 web server is available at https://lcbio.pl/cabsflex3. This website is free and open to all users, with no login requirement.