Abstract
Homologous proteins are special macromolecules with related primary sequences and multiple native structures and together with sequence-unrelated nonhomologous ones both constitute the protein amazing universe. Here is made a thorough sample selection, and employed quantitative predictions to analyze structures, conformations, steric and hydrophobic interactions and underlying molecular mechanisms in proteins via two coarse-grained (hydrophobic-polar, large-small) models. First, five empirical relations from nonhomologous samples are determined correlating large and hydrophobic residue sequences from primary to helix and β-sheet structures of functional conformations. When applied to homologous proteins, such empirical relations allow precisely surveying the interaction performance, identifying four types of molecular mechanisms, and computing the stability level in conformation ensembles. 1764 structural inspections capture essential features and furnish structural-interactional insights for homologous proteins, as well as suggest a fruitful way for better understanding conformational variability in biomolecular processes such as protein evolution, dynamics, folding and design.
Highlights
Proteins are specialized molecular machines vital for the existence and proper maintenance of all living organisms
One of the simplest ways of contemplating the extent of the sequence-structure gap is comparing proteins [7,8,9,10] by means of alignments between sequences and structures that can be summarized in four broad subsets: (1) alignment whose low residue sequence identity below 25% reveals unrelated proteins; (2) alignment with low sequence identity in distantly related proteins that have changed their sequences by evolution process and are generally clustered into common fold; (3) considerably high sequence identity (>25%) in proteins that usually have both structural and evolutionary relatedness and are assorted into a same family, in addition it is often assumed that such proteins possess similar structures; (4) alignment with very high sequence
In the sequence-structure context despite expressive research efforts, some relevant questions as the key acting of fundamental interactions, the driving mechanisms resulting from these interactions as well as their implications for analyzing conformation ensemble in homologous proteins are not fully understood, and such questions have been analyzed here by means of a rule-based approach
Summary
Proteins are specialized molecular machines vital for the existence and proper maintenance of all living organisms. The gap between the sequence and structure knowledge is inherently complex requiring a sum of many different driving forces and interactions, and involving a multitude of spatial and temporal scales, such that to predict unknown structures from the amino acid sequences alone still remain unsolved. Despite of this long-standing conundrum, many endeavors [1,2,3,4,5,6] have been done by researchers to reduce the protein sequence-structure gap since examining underlying principles and properties until advancing in applicative purposes, such as better understanding the biological and chemical activities of cells/organs, structure-based discovery of specific inhibitors, and to predict protein structures for rational structure based drug design in therapeutic insights, in the development of medicine, and to treat human diseases. The identity threshold in 25% can assume different values depending of the study method and approach utilized
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