What is the folding code? What is the folding mechanism? Can we predict the native structure of a protein from its amino acid sequence? Is it possible to predict the secondary, tertiary and quaternary structure of a polypeptide sequence based solely on the sequence and environmental information? Inverse protein-folding problem: Is it possible to design a polypeptide sequence which will adopt a given structure under certain environmental conditions? This was achieved for several small globular proteins in 2008.

The mechanisms of action of many drugs including lithium, thalidomide and ketamine are not completely understood. In cell theory, what is the exact transport mechanism by which proteins travel through the Golgi apparatus? How do cells determine what size to grow to before dividing? Many of these proteins are conserved across most eukaryotic species and some are conserved in bacteria, indicating a role fundamental for life.

What do all the unknown proteins do? Almost two decades since the first eukaryotes were sequenced, the 'biological role' of around 20% of proteins are still unknown.

See also: Hypothetical types of biochemistry What were the characteristics of the Last Universal Common Ancestor of Archaea, Bacteria, and Eukaryotes? Did Archaea and Eukaryotes evolve out of the domain Bacteria or to a clade basal to it? Do Archaea and Eukaryotes share a later or earlier common ancestor to Bacteria? How and why did cells combine to form the eukaryotic cell? Did one or more random events lead to the first eukaryotic cells, or can the formation of eukaryotic cells be explained by physical and biological principles? How did the mitochondria's mitosis cycle come in sync with its host cell? Did the mitochondria or the nucleus develop first in eukaryotes?

Origin of Eukaryotes ( Symbiogenesis).

How and why did the brain evolve? What are the molecular determinants of individual brain development? Exactly how and when did different groups of viruses originate? Exactly how, where, and when did life on Earth originate? Which, if any, of the many hypotheses is correct? What were the metabolic pathways used by the earliest life forms? General biology Evolution and origins of life This article lists notable unsolved problems in biology.

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