RT Journal Article
SR Electronic
T1 Where Natural Protein Sequences Stand out From Randomness
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 706119
DO 10.1101/706119
A1 Laura Weidmann
A1 Tjeerd Dijkstra
A1 Oliver Kohlbacher
A1 Andrei Lupas
YR 2019
UL http://biorxiv.org/content/early/2019/07/28/706119.abstract
AB Biological sequences are the product of natural selection, raising the expectation that they differ substantially from random sequences. We test this expectation by analyzing all fragments of a given length derived from either a natural dataset or different random models. For this, we compile all distances in sequence space between fragments within each dataset and compare the resulting distance distributions between sets. Even for 100mers, 95.4% of all distances between natural fragments are in accordance with those of a random model incorporating the natural residue composition. Hence, natural sequences are distributed almost randomly in global sequence space. When further accounting for the specific residue composition of domain-sized fragments, 99.2% of all distances between natural fragments can be modeled. Local residue composition, which might reflect biophysical constraints on protein structure, is thus the predominant feature characterizing distances between natural sequences globally, whereas homologous effects are only barely detectable.