Abstract
This paper discusses the sequence/structure relation. The core question concerns the degree to which similar sequences produce similar structures and vice versa. A mechanism by which similar sequences may result in dissimilar structures is proposed, based on the Fuzzy Oil Drop (FOD) model in which structural similarity is estimated by analyzing the protein’s hydrophobic core. We show that local changes in amino acid sequences, in addition to producing local structural alterations at the substitution site, may also change the shape of the hydrophobic core, significantly affecting the overall tertiary conformation of the protein. Our analysis focuses on four sets of proteins: 1) Pair of designer proteins with specially prepared sequences; 2) Pair of natural proteins modified (mutated) to converge to a point of high-level sequence identity while retaining their respective wild-type tertiary folds; 3) Pair of natural proteins with common ancestry but with differing structures and biological profiles shaped by divergent evolution; and 4) Pair of natural proteins of high structural similarity with no sequence similarity and different biological function.
Highlights
The presented analysis concerns the well-known problem of correlating the protein’s amino acid sequence with its 3D structure [14]
Our work focuses on structural differences in four pairs of proteins: 1) Pair of designer proteins with specially prepared sequences; 2) Pair of natural proteins modified to converge to a point of high-level sequence identity while retaining their respective wild-type tertiary folds; 3) Pair of natural proteins with common ancestry but with differing structures and biological profiles shaped by divergent evolution; and 4) Pair of natural proteins of high structural similarity with no sequence similarity and different biological function
The Fuzzy Oil Drop (FOD) model is a modification of the previously described oil drop model which asserts that hydrophobic residues tend to migrate to the center of the protein body while hydrophilic residues are exposed on its surface [23,24]
Summary
The presented analysis concerns the well-known problem of correlating the protein’s amino acid sequence with its 3D structure [14]. A classic example of this phenomenon is the group of structures referred to as immunoglobulin-like domains Such domains are present in all immunoglobulins (where they determine their function) but are encountered in enzymes and transport proteins [810]. The size of molecule shall be expressed by sigma parameters for Gauss function The characteristics of this function allows represent the hydrophobicity distribution with maximum in the center of ellipsoid with decrease together with the increase of distance versus the center reaching zero level in the distance equal to 3sigma in any direction. This idealized distribution ensures high solubility since the entire ellipsoid is covered by the hydrophilic shell
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