The Ten Commandments Of Protein Folding
One of the funniest posts I’ve ever read in the context of protein folding was written by Bosco K. Ho in his “Trapped in the USA” blog. It entails the ten commandments of protein folding which are:
I. Thou shalt have no other structure before the one true native structure.
II. Thou shalt not make unto thee any false structure of the native state, or any likeness of any structure such as predicted by molecular dynamics or homology modeling programs.
III. Thou shalt not take the name of the native structure in vain, and call by it any structure of RMSD greater than 4 angstroms. For I the Lord thy God is a jealous physicist, visiting the iniquity of the false believers of CASP upon their graduate students and postdocs unto the third and fourth generation; and shewing mercy unto humble crystallographers that keep my commandments.
IV. Remember the free energy landscape, to keep it holy and always go downhill. In milliseconds thou shalt sample conformations, but by the thousandth millisecond, thou shalt not labor, thou, nor thy side chains, nor thy backbones, nor thy disulfide bridges, nor thy binding partner that forms complex within thy active site: For in the thousandth millisecond the LORD placed thee in the free energy minimum, and blessed thy native state.
V. Honor thy hydrophobic residues; thou must bury them in thy core.
VI. Thou shalt not misfold.
VII. Thou shalt not aggregate.
VIII. Thou shalt not commit adultery unto the wrong binding partner.
IX. Thou shalt not denature in normal physiological conditions.
X. Thou shalt not covet thy neighbor’s structure, as designated by SCOP or CATH, nor his sequence, nor his function, for thy structure has been given thee by thy sequence alone.
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