Institute of Organic Chemistry and
Biochemistry, Centre for Complex Molecular Systems and Biomolecules, Flemingovo
nam. 2, Prague 6, 166 10, Czech Republic
The protein
structure is to a large extent determined by the interactions of its residues. The
aromatic residues are able of hybrid interactions with several partners at
once. Hence there is a strong need for studying the interactions of these
residues. However, the assessment of the strength of their interactions is very
complicated and not that straightforward as for classical H-bond. We decided to
study the interactions on the best theoretical level available on one model
system. This gives us a good reference for other, “cheaper” methods and
provides us with some ideas about the roles an aromatic residue can play in the
protein interior.
Our primary criterion for the model
system selection was a high X-ray structure quality and a presence of a densely
packed cluster of aromatic residues with a phenylalanine having at least five
residues closer than 4Å. We have chosen a small (52 AAs) thermostable FeS
protein rubredoxin (desulfovibrio vulgaris)
which is assumed to serve as an electron transfer protein. The hydrophobic core
of the protein is constituted of several aromatic and aliphatic residues. For
the purpose of our study we have chosen Phe30 which has in its vicinity an
extraordinary number of interacting partners of different character. The
residue is acting at once in CH/π, π/π, kation/π, anion/π
(the sidechain) interactions as well as in a classical H-bond (the mainchain). The
interaction energies of the central Phe30 with its partners represented as isolated amino acid molecules were
calculated in vacuo using high-level ab
initio methods. The positions of all non-hydrogen atoms were held fix at
the X-ray structure geometry, while the position of all hydrogen atoms was
optimized at the DFT/6-31G** level. The interaction energy was then calculated
as the sum of two contributions; one being an RI-MP2 interaction energy
extrapolated to the basis set limit, the other a correction term for higher
order (CCSD(T)) correlation energy. As a test of the reliability of various empirical
potentials we have computed the interaction energies of the same systems in
several common forcefields.
Our present
results show that there is a strong interaction of Phe30 with the surrounding
residues without any repulsion. Such
strength could be the reason for thermostability of the protein and also an
origin of the folding process. There is pronounced difference in the
performance of the tested forcefields. Some forcefields proved to be able to
reproduce the results of the reference method.