A Computational Genome-wide Study of Protein Folding Rate
thesisposted on 2012-12-13, 00:00 authored by Sandeep C. Gorla
Proteins should be able to ‘fold’ to a native three-dimensional structure in a biologically relevant time to be functional. In our current study, we tried to gain insight into this complex process of protein folding by studying the folding rate distributions in a proteome.We used a folding rate prediction model based on the evaluation of the contribution of pairs of sequentially neighboring amino acids to the folding rate. We used this model to compute the proteome-wide distributions of folding rates of several model organisms. We looked at the extreme limits of these distributions and see that many slow folding proteins in a cell require the help of the chaperone machinery to fold in a biologically relevant time. On analyzing the folding rate distributions in extremophiles we see that halophiles have a different folding rate distribution when compared to mesophiles. We further identified the fastest and slowest folders among representative sequences of all known protein families. We analyzed certain structures among these fast/slow folders to gain valuable insight into the relationship between structure and the folding rate of a protein.