The Multi-Scale 3D-1D compatibility scoring for inverse protein folding problem.

Abstract

The applicability of the Multi-Scale Structure Description (MSSD) scheme to the inverse-folding problems was investigated. An MSSD represents a 3D protein structure with multiple symbolic sequences, where fine structures are represented with the sequence at low levels, the middle scale structural motifs at middle levels, and global topology at high levels. Each symbol in the symbolic sequence denotes a type of local structure of the level scale. The structure fragments are classified at each scale level respectively according to the shape and the environment around the fragments: how the structure is exposed to the solvent or buried in the molecule. I modeled the propensity of an amino-acid sequence to the structure fragment type (i.e., primary constraint) at each scale level. The local propensity is, therefore, modeled at small scale (low) levels, while the global propensity modeled at large scale (high) levels. Thus, superposing all the primary constraint, a 3D protein structure yields an amino-acid sequence profile. Evaluating the fit of an amino acid sequence to the profile derived from the known 3D protein structure, we can identify which 3D structure the given amino-acid sequence would fold into. I checked whether a sequence identifies its own structure over two hundred protein sequences. In many cases, an amino acid sequence identified its own 3D protein structure.