The potential energy landscape perspective provides both a conceptual and a computational framework for predicting, understanding and designing molecular properties. In this Feature Article, we highlight some recent advances that greatly facilitate structure prediction and analysis of global thermodynamics and kinetics in proteins and nucleic acids. The geometry optimisation procedures, on which these calculations are based, can be accelerated significantly using local rigidification of selected degrees of freedom, and through implementations on graphics processing units. Results of progressive local rigidification are first summarised for trpzip1, including a systematic analysis of the heat capacity and rearrangement rates. Benchmarks for all the essential optimisation procedures are then provided for a variety of proteins. Applications are then illustrated from a study of how mutation affects the energy landscape for a coiled-coil protein, and for transitions in helix morphology for a DNA duplex. Both systems exhibit an intrinsically multifunnel landscape, with the potential to act as biomolecular switches.

Among biomolecules, nucleic acids, namely DNA and RNA, have the unique function of storing an organism’s genetic code the sequence of nucleotides that determines the amino acid sequence of proteins, which are of critical importance to life on Earth. There are 20 different amino acids that can occur within a protein; the order in which they occur plays a fundamental role in determining protein structure and function. Proteins themselves are major structural elements of cells. They also serve as transporters, moving nutrients and other molecules in and out of cells, and as enzymes and catalysts for the vast majority of chemical reactions that take place in living organisms. Proteins also form antibodies and hormones, and they influence gene activity.

Carbohydrates, which are made up primarily of molecules containing atoms of carbon, hydrogen, and oxygen, are essential energy sources and structural components of all life, and they are among the most abundant biomolecules on Earth. They are built from four types of sugar units—monosaccharides, disaccharides, oligosaccharides, and polysaccharides.

Lipids, another key biomolecule of living organisms, fulfill a variety of roles, including serving as a source of stored energy and acting as chemical messengers. They also form membranes, which separate cells from their environments and compartmentalize the cell interior, giving rise to organelles, such as carbohydrates, which are made up primarily of molecules containing atoms of carbon, hydrogen, and oxygen, are essential energy sources and structural components of all life, and they are among the most abundant biomolecules on Earth.

All biomolecules share in common a fundamental relationship between structure and function, which is influenced by factors such as the environment in which a given biomolecule occurs. Lipids, for example, are hydrophobic (“water-fearing”); in water, many spontaneously arrange themselves in such a way that the hydrophobic ends of the molecules are protected from the water, while the hydrophilic ends are exposed to the water. This arrangement gives rise to lipid bilayers, or two layers of phospholipid molecules, which form the membranes of cells and organelles. In another example, DNA, which is a very long molecule in humans, the combined length of all the DNA molecules in a single cell stretched end to end would be about 1.8 metres (6 feet), whereas the cell nucleus is about 6 μm (6 10^-6 metre) in diameter has a highly flexible helical structure that allows the molecule to become tightly coiled and looped.

Best Regards,
Nicola B
Editorial Manager
Journal of Biochemistry & Biotechnology