To form stable connections to your neighbors is a way to make daily life predictable even if the relations are inimical. Looking at an amino acid in a three-dimensional structure is likewise to look for neighbors at the amino acid level. This problem of protein folding has occupied biochemists for quite some time. Even with the biggest supercomputers it could not sufficiently be simulated.
In a Perspective article in PNAS Englander and Mayne from the Univ. Pennsylvania present the problem and the new technology which has helped to solve at least one structure’s folding. They show what is possible now and what cannot be done. At the origin of the problem are small units of folding which the form or donot form extended structures. Deuterium/hydrogen exchange experiments and their fast time-line-records are what can give information about the ways protein fold. This is an actual picture what has been achieved in the field. It is more that one could expect from the outside, but not enough to solve the puzzle. It seems at least that a mechanism of protein folding has been found.