Generating artificial homologous proteins according to the representative family character in molecular mechanics properties – an attempt in validating an underlying rule of protein evolution

AbstractThe molecular mechanics property is the foundation of many characters of proteins. Based on intramolecular hydrophobic force network, the representative family character underlying a protein’s mechanics property is described by a simple two-letter scheme. The tendency of a sequence to become a member of a protein family is scored according to this mathematical representation. Remote homologs of the WW-domain family could be easily designed using such a mechanistic signature of protein homology. Experimental validation showed that nearly all artificial homologs have the representative folding and bioactivity of their assigned family. Since the molecular mechanics property is the only consideration in this study, the results indicate its possible role in the generation of new members of a protein family during evolution

Major factors of protein evolution revealed by eigenvalue decomposition analysis

Here we attempt to characterize protein evolution by its dominant factors. These factors are revealed by top eigenvectors in the spectrums of eigenvalue decomposition analysis. To reduce the bias induced by closely related sequences in the database, we introduce a parameter, sequence identity by which proteins with sequence identity below certain level are involved in analysis. It is found that, with drop of sequence identity level, residue feature mainly conserved in mutation changes from hydrophobicity to volume. The transition point is at sequence identity 45%. As residue hydropho-bicity no longer governs residue substitution, it is a doubt whether importance of hydrophobic interaction declines in conserving the family representative properties among remote homologues. So, we also investigate the contribution of hydrophobic interaction in near and remote homologues. In aligned homologues, hydrophobic interaction systems inbuilt in these proteins are aligned too; and can be deemed to be similar and substitutable with each other. With a comparison of aligned hydrophobic interaction systems, we can catch the representative character of hydrophobic interaction for the corresponding protein family. Here top weighted feature in the substitution of hydropho-bic interaction systems is revealed as a function of sequence identity. It is found that a shift happens to the type of physical quantity which governs the substitution of hydrophobic interaction. The number of hydrophobic residue is the dominantly unchangeable part in aligned hydrophobic interactions as sequence identity > 30%. Below this point, state of internal hydrophobic force which characterizes the residue-residue pairwise interaction is primarily conserved. With view of this shift, intrinsic requirement of protein evolution is sought in the discussion section