ThermoPCD: a database of molecular dynamics trajectories of antibody-antigen complexes at physiologic and fever-range temperatures.

Abstract

Progression of various cancers and autoimmune diseases is associated with changes in systemic or local tissue temperatures, which may impact current therapies. The role of fever and acute inflammation-range temperatures on the stability and activity of antibodies relevant for cancers and autoimmunity is unknown. To produce molecular dynamics (MD) trajectories of immune complexes at relevant temperatures, we used the Research Collaboratory for Structural Bioinformatics (RCSB) database to identify 50 antibody:antigen complexes of interest, in addition to single antibodies and antigens, and deployed Groningen Machine for Chemical Simulations (GROMACS) to prepare and run the structures at different temperatures for 100-500 ns, in single or multiple random seeds. MD trajectories are freely available. Processed data include Protein Data Bank outputs for all files obtained every 50 ns, and free binding energy calculations for some of the immune complexes. Protocols for using the data are also available. Individual datasets contain unique DOIs. We created a web interface, ThermoPCD, as a platform to explore the data. The outputs of ThermoPCD allow the users to relate thermally-dependent changes in epitopes:paratopes interfaces to their free binding energies, or against own experimentally derived binding affinities. ThermoPCD is a free to use database of immune complexes' trajectories at different temperatures that does not require registration and allows for all the data to be available for download. Database URL: https://sites.google.com/view/thermopcd/home.