Time to recap? The Molecular Design of Life, focuses on molecular models, noncovalent bonds and water.
An introduction to the three types of atomic models used to depict molecular architecture includes; space-filling, ball and stick, and skeletal. The space-filling is the most realistic. Although the ball and stick is not as realistic, the bonding arrangements are visually apparent. The skeletal provides a molecular framework.
Space filling image of ATP
Following on to scale, time and energy we are first introduced to units of measurements. The unit used to measure the length of an atomic level is angstrom Å. [1 angstrom (Å) = 10–10 meters = 0.1 nm = 100 pm]
The molecules of life are constantly in flux.
Chemical reactions are catalyzed by enzymes covert substrates into products in milliseconds (ms). The unwinding of DNA helix is a microsecond event (µs), the hinge motion of proteins occurs in a nanosecond (ns) and primary event in vision occurs within a few picoseconds (ps). On energy changes in molecular events, the sun is the ultimate source of energy. The universal currency of energy is Adenosine Triphosphate (ATP). ATP has usable energy content of 12 kcal/mol. The average energy of each vibrational degree of freedom in a molecule is much smaller, 0.6 kcal/mol at 25°C. So it’s much smaller than energy needed to separate covalent bonds. Thus the covalent framework of biomolecules is stable in absence of enzymes and energy. Noncovalent bonds have energy of few kcal/mol that thermal energy is enough to make/break them.
3D model of ATP
Reversible molecular interactions are at the heart of dance of life.
A key role in the accurate replication of DNA, folding of proteins into 3D forms, recognition of substrates by enzymes, and detection of signals lies in the weak noncovalent forces; electrostatic bonds, hydrogen bonds, and van der Waals bonds. Biological structures and processes depend on interplay of noncovalent interactions and covalent ones.
The electrostatic bond’s attraction is strongest in vacuum and weakest in water. The hydrogen bond is highly directional and stronger than van der Waals but weaker than covalent. The DNA double helix is held together by hydrogen bonds between bases on opposite strands. Van der Waals bonds, though weaker and less specific than electrostatic and hydrogen bonds, it’s no less important. It occurs when two atoms are 3-4 Å apart. The attraction increases as the pair of atoms move closer until separated by van der Waals contact distance. The importance of this bond comes into play when numerous atoms in one pair of molecules can simultaneously come close to many atoms of the other (if shapes match). Specificity arises when there is a large chance to make a large number of van der Waals bonds simultaneously. The repulsions (contact distance) are as important as attractions for establishing specificity.
Snapshot from a simulation of liquid water.
The four thin green lines from the molecule in the center of the picture represent hydrogen bonds.
We now enter the water zone - how water influences all molecular interactions in biological systems. There are two important properties for water. One is its polarity and the other is its cohesiveness. The triangular shape of the water molecule allows for its asymmetrical distribution of charge. The oxygen nucleus draws electron away from hydrogen nuclei resulting in a net positive charge, thus water molecule is electrically polar structure. A positively charged regions in one water molecule tends to orient itself to a negatively charged region in one of its neighbours.
In ice, all potential hydrogen bonds are made and in liquid, the hydrogen bonded clusters of molecules are continuously forming and breaking. Each molecule is hydrogen bonded to average 3.4 neighbours in liquid and 4 in ice. Thus water is highly cohesive.
Water’s polarity and hydrogen bonding capacity makes it a highly interacting molecule and good solvent for polar molecules. The reason is that water weakens electrostatic forces and hydrogen bonding between polar molecules by competing for their attraction.
The existence of life depends on the capacity of water to dissolve large array of polar molecules. High concentration of these molecules can co-exist in water free to diffuse and find each other. However, water as a solvent poses the problem that is also weakens the interactions between polar molecules. Biological systems solved this issue by create water-free environments where polar interactions have maximal strength.
Nonpolar molecules or groups tend to group and cluster together in water. These associations are called Hyrdophopic Attractions. These form major driving force in, folding of macromolecules, binding of substrates to enzymes, formation of membrane that defines boundaries of cells and internal compartments.