Protein-Solvent Interactions: Water, Ions, Lipids, and Crowding

immune system. The stability of the interaction between MHC class I and pep-tideisgovernedbylengthandsequenceofthepeptide.Thecarboxylandaminotermini of the peptide make a significant contribution to binding energy byforming networks of hydrogen bonds. In addition, the carboxy terminal sidechain of the peptid serves as an anchor residue in all the known MHC class Ialleles, i.e., it binds into a pocket at the bottom of the binding site.We show here that the binding of the carboxyl terminus of the peptide has astrong influence on the dynamics, binding energy, folding, peptide affinityandstabilityonthecellsurfaceoftwoMHCclassImouseallotypes.MolecularMechanic/ Poisson-Boltzmann Surface Area (MM-PBSA) and potential meanforce (PMF) analysis demonstrate that binding of the the carboxy terminuscauses a decrease in the peptide free binding energy to MHC class I. This isverified in vitro by thermal denaturation by tryptophan fluorescence (TDTF)and Fluorescence anisotropy (FA) assays, which show a considerable decreasein the thermal stability and peptide binding affinity of C-terminally truncatedpeptides to class I. Such truncated peptides are also much less efficient in sta-bilizing MHC class I at the cell surface.3355-Pos Board B83Mechanistic Insights of b-Lactmases EvolutionTaisong Zou