PK(A) SHIFT EFFECTS ON BACKBONE AMIDE BASE-CATALYZED HYDROGEN-EXCHANGE RATES IN PEPTIDES

Amide proton exchange (HX) rates are known to depend on protein primar y structure as well as local and global protein structure and dynamics . Measurement of HX rates gives information on the local exposure of a mide protons to solvent and on local rates of structural openings. It has long been recognized that the amide pK(a) directly influences the HX rate. Using the finite-difference solution of the Poisson-Boltzmann equation, we investigated the electrostatic effects on HX rates, via calculated shifts in the amide pK(a) for model compounds (N-methylacet amide, dipeptides entailing almost all amino acid side chains, and a t ripeptide). Rather than shifts in the same compound with varying envir onmental conditions, we address shifts in the HX rates of different co mpounds relative to each other. The results for selected model compoun ds which resemble Ala and Gly residues, with a standard choice of para meters, agree to a high degree of accuracy with experimentally determi ned rates. Application of the same methodology to naturally occurring amino acids is promising but requires refinement to take into account flexibility and inductive effects.