Book of Abstracts: Albany 2007

category image Albany 2007
Conversation 15
June 19-23 2007

Aspartic and Glutamic Acids are Important for Alpha-helix Folding

Influence of amino acid sequence on formation one or another type of secondary structure of protein is still one of the most actual problems in classical proteomics and in modern bioengineering. One of the most popular hypotheses of folding is the "framework model". It proclaims the importance of forming embryonic alpha-helices and beta-sheets on early stages of folding. However, the question, how unfolded coils starts a one or another shape of polypeptide chain, is empirical in many respects, and the mechanism of the full process remains unclear.

It is generally known, that amino acid sequence contains all necessary information for protein structure. There are many well known individual characteristics (structure, spectral, and thermodynamic data) of amino acids and most simple peptides. As addiction, we have accumulated enough data about favorable location for each of 20 basic amino acids in different types of secondary structure elements of a protein and we can simulate kinetics of linear polypeptide sequence.

This work is devoted to studying alpha-helix folding mechanism by means of two computing techniques: molecular mechanics and semiempirical ??3 quantum-chemistry. We have performed analysis of structure and thermodynamic properties of model oligopeptides, which contain Asp and Glu residues in their structure, both in neutral, and in charged forms. Our previous work showed, that these two residues have special conformers with intramolecular hydrogen bonds of two types: single and bifurcational. Now we have found that most likely, the Asp and Glu residues put in order the following residues and make the first helix turn easier.

We made a different MD-calculations for some model and native oligopeptides: DGGGGGGG, DAAAAAAA, DVVVVVVV, DFFFFFFF, EGGGGGGG, EAAAAAAA, EVVVVVVV, EFFFFFFF, lyzocime (PDB-entry 107L, 1-13 residues), and parvalbumine (PDB-entry 4CPV, 59-70 residues), compared their speeds of helication and discuss the details of mechanism of alpha-helix forming. Also the dependency of this effect on Asp and Glu positions in the sequence has been analyzed.

Maxim Kondratiev*
Artem Kabanov
Alexander Samchenko
Vladislav Komarov

Institute of Cell Biophysics
Puschchino, Russia

*Email: ma-ko@bk.ru