Conformational Ensembles from Experimental Data and Computer Simulations

Conformational Ensembles from Experimental Data and Computer Simulations

Poster Abstracts

3-POS Board 3 Peptide Tuning of MHC Protein Energy Landscapes: A Key Aspect of Antigen Presentation and Recognition in the Immune System Cory Ayres, Brian Baker . University of Notre Dame, Notre Damne, IN, USA. Major histocompatibility complex (MHC) proteins bind and "present" peptides for recognition by T cells of the immune system. Through a combination of structural biology and solution biophysics, we previously demonstrated that different peptides “tune” the energy landscapes of MHC proteins. The consequences of this tuning on the motional properties of MHC proteins impacts recognition by T cell receptors of the immune system. To explore this phenomenon in more detail, here we describe the creation and analysis of a large library of molecular simulations of different peptides bound to the most common class I MHC protein, HLA-A2. Nearly 100 different peptide/HLA-A2 complexes were simulated for 1 microsecond, generating a rich dataset of MD data for the same protein bound to different peptides. We identified key residues that are important in tuning of HLA-A2 dynamics and show that the HLA-A2 energy landscape is modulated such that protein dynamics are altered across the protein. Altered dynamics are transmitted not only to sites that interact with T cell receptors, but sites that interact with other activating and inhibitory immune receptors and components of the peptide loading and editing machinery. We propose that modulation of the energy landscape of MHC proteins is a key aspect of antigen presentation and recognition in the immune system.

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