Structural modeling and computational analyses of immune system molecules

The host immune system may differentially respond to environmental agents, inducing or failing to induce an effective response. Much progress has been made to understand the structure of the immune system molecules, particularly with the use of X-ray crystallography and other structural methods. However, due to limitations of crystallography and other methods, important features regarding the structure and dynamics of many immune system molecules remain undetermined. In this context, in silico studies have provided key insights and methods to bridge this gap, enabling the modeling and analysis of the 3D structure and dynamics of small molecules, proteins up to macro-molecular complexes, which drive complex immunological phenomena. Progress in this area is bound to accelerate even further, with the advent of (i) new experimental methods (e.g., cryogenic electron microscopy, hydrogen-deuterium exchange mass spectrometry), (ii) the growing use of machine learning to improve structural modeling (e.g., AlphaFold, RoseTTAFold), and (iii) increasing availability of large datasets through online databases dedicated to molecules involved in the immune system.

This Research Topic focuses on the molecular 3D structure and dynamics of immune system molecules, providing information that goes beyond the capabilities of existing experimental methods. We aim at fostering the use of innovative computational methods alone, or in combination with alternative sources of experimental data, to provide new insights into the structure and function of molecules of the immune system. Considering that one of the main challenges related to computational modeling is the validation of results, new computational methods that can leverage available data to enable in silico validation are also greatly needed and encouraged.

In this research topic, we welcome the submission of contributions on all molecules that participate in the innate and/or adaptive immune system, particularly focusing, but not exclusively, on:
● modeling and simulation of cytokine/chemokine molecules and interactions with their respective receptors
● modeling and simulation of interactions of downstream mediators
● modeling and simulation of transcription factors interacting with DNA
● structural analysis of microRNA/mRNA interactions involved in the modulation of immune system genes
● structural analyses of histocompatibility antigen diversity impact on interactions with peptide-binders and T-cell receptors
● modeling T-cell receptors and other leukocyte receptors
● computer-aided prediction of unknown binders of immune checkpoint molecules (e.g., inhibitors or agonists)
● modeling of chimeric or engineered receptors for immunotherapy applications
● use of computational methods to refine or understand experimental data (e.g., ensemble refinement of crystal structures, molecular replacement of crystallographic data with AlphaFold2 or RoseTTAFold)
● combination of detailed computational modeling with low-resolution experimental methods (e.g., HDX-MS) to determine protein structure of immune system proteins/complexes.

Keywords: immune system molecules, molecular modeling, molecular docking, molecular dynamics, structural analyses

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.