Authors: Feng, Yuanming
Gao, Shan
Ruan, Jishou
Zhang, Ning
Zhang, Tao
Title: New insights of protein folding as learned from beta-sheets
Language (ISO): en
Abstract: The folding of denatured proteins into their native conformations is called Anfinsen’s dogma, and is the rationale for predicting protein structures based on primary sequences. Through the last 40 years of study, all available algorithms which either predict 3D or 2D protein structures, or predict the rate of protein folding based on the amino acid sequence alone, are limited in accuracy (80 %). This fact has led some researchers to look for the lost information, from mRNA to protein sequences, and it encourages us to rethink the rationale of Anfinsen’s dogma. In this study, we focus on the relationship between the strand and its partners. We find two rules based on a non-redundant dataset taken from the PDB database. We refer to these two rules as the “first coming first pairing” rule and the “loveless” rule. The first coming first pairing rule indicates that a given strand prefers to pair with the next strand, if the connected region is flexible enough. The loveless rule means that the affinities between a given strand and another strand are comparable to the affinity between the given strand and its partner. Of course, the affinities between the given strand and a helix/coil peptide are significantly less than the affinity between the given strand and its partner. These two rules suggest that in protein folding, we have folding taking place during translation, and suggest also that a denatured protein is not the same as its primary sequence. Rechecking the original Anfinsen experiments, we find that the method used to denature protein in the experiment simply breaks the disulfide bonds, while the helices and sheets remain intact. In other words, denatured proteins still retain all helices and beta sheets, while the primary sequence does not. Although further verification via biological experiments is needed, our results as shown in this study may reveal a new insight for studying protein folding.
Subject Headings: helix
near-neighbor pairing
protein folding
Issue Date: 2012-11-16
Appears in Collections:Original Articles

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