LINUS: A hierarchic procedure to predict the fold of a protein

We describe LINUS, a hierarchic procedure to predict the fold of a protein from its amino acid sequence alone. The algorithm, which has been implemented in a computer program, was applied to large, overlapping fragments from a diverse test set of 7 X‐ray‐elucidated proteins, with encouraging results. For all proteins but one, the overall fragment topology is well predicted, including both secondary and supersecondary structure. The algorithm was also applied to a molecule of unknown conformation, groES, inwhich X‐ray structure determination is presently ongoing. LINUS is an acronym for L ocal I ndependently N ucleated U nits of S tructure. The procedure ascends the folding hierarchy in discrete stages, with concomitant accretion of structure at each step. The chain is represented by simplified geometry and folds under the influence of a primitive energy function. The only accurately described energetic quantity in this work is hard sphere repulsion–the principal forceinvolved in organizing protein conformation [Richards, F. M. Ann. Rev. Biophys. Bioeng. 6:151–176, 1977]. Among other applications, the method is a natural tool for use in the human genome initiative. © 1995 Wiley‐Liss, Inc.