Acidic-basic properties of three alanine-based peptides containing acidic and basic side chains: Comparison between theory and experiment
✍ Scribed by Joanna Makowska; Katarzyna Bagińska; Adam Liwo; Lech Chmurzyński; Harold A. Scheraga
- Publisher
- Wiley (John Wiley & Sons)
- Year
- 2008
- Tongue
- English
- Weight
- 324 KB
- Volume
- 90
- Category
- Article
- ISSN
- 0006-3525
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✦ Synopsis
Abstract
The purpose of this work was to evaluate the effect of the nature of the ionizable end groups, and the solvent, on their acid‐base properties in alanine‐based peptides. Hence, the acid‐base properties of three alanine‐based peptides: Ac‐KK‐(A)~7~‐KK‐NH~2~ (KAK), Ac‐OO‐(A)~7~‐DD‐NH~2~ (OAD), Ac‐KK‐(A)~7~‐EE‐NH~2~ (KAE), where A, D, E, K, and O denote alanine, aspartic acid, glutamic acid, lysine, and ornithine, respectively, were determined in water and in methanol by potentiometry. With the availability of these data, the ability of two theoretical methods to simulate pH‐metric titration of those peptides was assessed: (i) the electrostatically driven Monte Carlo method with the ECEPP/3 force field and the Poisson‐Boltzmann approach to compute solvation energy (EDMC/PB/pH), and (ii) the molecular dynamics method with the AMBER force field and the Generalized Born model (MD/GB/pH). For OAD and KAE, p__K__~a1~ and p__K__~a2~ correspond to the acidic side chains. For all three compounds in both solvents, the p__K__~a1~ value is remarkably lower than the p__K__~a~ of a compound modeling the respective isolated side chain, which can be explained by the influence of the electrostatic field from positively charged ornithine or lysine side chains. The experimental titration curves are reproduced well by the MD/GB/pH approach, the agreement being better if restraints derived from NMR measurements are incorporated in the conformational search. Poorer agreement is achieved by the EDMC/PB/pH method. © 2008 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 90: 724–732, 2008.
This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at [email protected]