Protein Design using native secondary sub-structures

According to structure-dependent function of proteins, two main challenging problems called Protein Structure Prediction (PSP) and Inverse Protein Folding (IPF) are investigated. In spite of IPF essential applications, it has not been investigated as much as PSP problem.

In fact, the ultimate goal of IPF problem or protein design is to create proteins with enhanced properties or even novel functions. One of the major computational challenges in protein design is its large sequence space, namely searching through all plausible sequences is impossible. Inasmuch as, protein secondary structure represents an appropriate primary scaffold of the protein conformation, undoubtedly studying the Protein Secondary Structure Inverse Folding (PSSIF) problem is a quantum leap forward in protein design, as it can reduce the search space.

In this software, a novel genetic algorithm which uses native secondary sub-structures is proposed to solve PSSIF problem. In essence, evolutionary information can lead the algorithm to design appropriate amino acid sequences respective to the target secondary structures. Furthermore, they can be folded to tertiary structures almost similar to their reference 3D structures.

The proposed algorithm called GAPSSIF benefits from evolutionary information obtained by solved proteins in the PDB. Therefore, we construct a repository of protein secondary structure elements to accelerate convergence of the algorithm.

The secondary structure of designed sequences by GAPSSIF is comparable with those obtained by Evolver and EvoDesign. Although we do not explicitly consider tertiary structure features through the algorithm, the structural similarity of native and designed sequences declares acceptable values.

Using the evolutionary information from proteins with native structure can significantly improve the quality of designed sequences. In fact, the combination of this information and effective features such as solvent accessibility and torsion angles leads IPF problem to an efficient solution.

Downloads

  1. Download the stand-alone version of GAPSSIF(7.6 MB) and its repository (the software is a linux-executable file and does not need any installation).
  2. Download Documentation(7.9 kB) for a full description of the software.
  3. Download our non-redundant dataset(26.2 kB). This benchmark contains 89 non-redundant proteins with different length and SCOP class.
  4. Download the 2D-3D bechmark(150 kB) used for 2D and 3D evaluation of designed sequences by GAPSSIF. This dataset contains 5 proteins alongside their edited pdb files.

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