Document Detail


Acidic-basic properties of three alanine-based peptides containing acidic and basic side chains: comparison between theory and experiment.
MedLine Citation:
PMID:  18618612     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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, pK(a1) and pK(a2) correspond to the acidic side chains. For all three compounds in both solvents, the pK(a1) value is remarkably lower than the pK(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.
Authors:
Joanna Makowska; Katarzyna Bagińska; Adam Liwo; Lech Chmurzyński; Harold A Scheraga
Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Biopolymers     Volume:  90     ISSN:  0006-3525     ISO Abbreviation:  Biopolymers     Publication Date:  2008  
Date Detail:
Created Date:  2008-11-03     Completed Date:  2008-12-16     Revised Date:  2013-01-09    
Medline Journal Info:
Nlm Unique ID:  0372525     Medline TA:  Biopolymers     Country:  United States    
Other Details:
Languages:  eng     Pagination:  724-32     Citation Subset:  IM    
Affiliation:
Faculty of Chemistry, University of Gdańsk, Sobieskiego 18, 80-952 Gdańsk, Poland.
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MeSH Terms
Descriptor/Qualifier:
Alanine / chemistry*
Amino Acids, Acidic / chemistry*
Amino Acids, Basic / chemistry*
Hydrogen-Ion Concentration
Kinetics
Methanol / chemistry
Models, Chemical
Peptides / chemical synthesis,  chemistry*
Potentiometry
Protein Conformation
Solvents
Static Electricity
Water / chemistry
Grant Support
ID/Acronym/Agency:
GM-14312/GM/NIGMS NIH HHS; R01 GM014312/GM/NIGMS NIH HHS; R01 GM014312-53/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Amino Acids, Acidic; 0/Amino Acids, Basic; 0/Peptides; 0/Solvents; 56-41-7/Alanine; 67-56-1/Methanol; 7732-18-5/Water
Comments/Corrections

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