Chapter 1. Intra- and intermolecular interactions in biologically active molecules. structure of peptides, proteins, dna and pna

(Tamás Körtvélyesi)

1.  Introduction

The main compounds in the living cells are peptides, proteins, lipids, sugars, phospholipids, DNA, water and salts, etc. with different functions (structural molecules, enzymes, etc.). These molecules and ions are important in working of living cells. The main interactions in biomolecules are described in this chapter. Some of the biomolecules are depicted by animations to study the building blocks of the molecules.We do not show the molecules, the classes of molecules, because the reader can find these information in a lot of excellent textbooks.

2.  Intramolecular Interactions Stabilizing the Structure

2.1. Peptide bonds

The 20 native aminoacids (with L-chirality) can bind to each other by peptide bonds. The four-atom link is called peptide link (http://en.wikipedia.org/wiki/Peptide_bond). Peptide bonds are mainly trans peptide binding of residues. The –C(=O)NH is a resonance stabilized structure which is planar. It is sensitive to water and pH, and they can break easily (that is why the peptides can not be used as drugs through mouth). In some cases – mainly at Pro the ratio of the cis/trans isomers is 1:3. (It is a good possibility for the validation of MD.)

„Within three, four or five residues, the turns are assigned on the basis of the position of the H-bond between the residues, i to i+2 to i+3 and i to i+4. A turn is marked at position i to i+1 for the three residue turn, i+1 to i+2 for a four residue turn, and i+1, i+2, i+3 for a five residue turn. A β-bridge is assigned when two non overlapping stretches of three residues each, i-1,i,i+1 and j-1,j,j+1 form a hydrogen bonding pattern consistent with either parallel or antiparallel β-structures and is marked at the i and j residues. β-sheet is defined by more consecutive β-bridges. The bend is defined as a five residue turn without H bondsTwo consecutive turns at position i-1and i form a 3₁₀-helix which is marked at i, i+1 and i+2. α-helix at i, i+1, i+3 and π-helix at i, i+1, i+2, i+3, i+4” [1,2].

2.2. Salt bridges

Strong electrostatic interactions are due to the attraction of positive-negative charges of groups or the repulsion of the same charges. Thy have great effect on t he stability of the structures and ont he formation of secondary, tertiary and quatarnary structures in proteins and in the other biomolecules (see later) [1]. The electrostatic interactions can be calculated by the Coulomb equation (see Chapter 1). The Coulomb interactions are not only between the groups with integer charges (Lys, Asp, Glu, Arg, etc.), but between groups with partial charges (see Lit. [2,3]).

2.3. H-Bonds

Pauling [4] suggested a secondary bond which can be characterized by X-H…Y where X and Y as pilar atoms have greater electronegativity [3]. The energy stability is increasing and the geometries are deformed. F−H…:F (161.5 kJ/mol), O−H…:N (29 kJ/mol), O−H…:O (21 kJ/mol), N−H…:N (13 kJ/mol), N−H…:O (8 kJ/mol), HO−H…:OH (18 kJ/mol). X−H…Y system: X−H distance is typically ca. 110 pm, http://en.wikipedia.org/wiki/Picometre \o "Picometre" whereas H…Y distance is ca.160 to 200 pm. As it can be seen, the stabilization energies are much more lower than the chemical bonds. Bondi suggested a geometrical description of H-bonds [5]. H-bond can be defined by the van der Waals radiuses and angles. If the distance of the pilar atoms (X, Y) is less than the sum of the van der Waals radii and the angle of X-H…Y is greater than 90 degree (and less than 180 degree). The best computational method to recognize the H-bonds is DSSP [6] which was developed by Kabsch and Sanders [7].

2.4. π- π, π-HN, π-HO and π-H₃N⁺ Stacking

Figure 1.1. π-π stacking between aromatic groups

2.5.  Hydrophobic Interactions

Interactions with dispersion are important between molecules (e.g. alkanes) without charges [13]. The alkane/water and octanol/water partition coefficients are important in drug design to predict the solution of drug molecules in the cells. The possibility of the predictions of the partition coefficients are summerized in Lit. [13].

2.6. Protein-metal complexes

A lot of metals can bind to the proteins (Zn, Fe, Co, Mg, etc). They have basic roles in the biochemical reactions (see e.g. Zn-fingers, heamoglobine, etc.).

3.  Peptides and Proteins Structures

Figure 1.2. Natural aminoacids classified by the polarity of the side-chain

Figure 1.3. βA(1-40) amyloid peptide structure with sequence (PDB Id.: 1aml)