Protein structure- Threading

1. Institute Of Pharmaceutical Sciences
TOPIC - Threading Protein Modelling
SUBMITTED BY-
Vidhi sharma
SUBMITTED TO-
Dr. Ritu

2. Threading
● Threading = Placing or Aligning
● Protein threading is a bioinformatics technique used to predict the
three-dimensional structure of a protein based on its amino acid
sequence. The method involves threading, or aligning, the target
protein sequence .
● Goal - is to identify the most energetically favorable or biologically
relevant fold for a given protein sequence
● This computational approach helps bridge the gap between protein
sequence and structure prediction,
Placed into by force

3. Protein Structure Prediction

4. Need of Threading
● Sequence of Homology<20 %
● Fold Recognition
● No 3D Structure Formality
● Computational Limitations

5. Protein Threading v/s Fold Recognition
Protein Threading
● protein threading, the primary sequence of a
target protein is compared against a
database of known protein structures
.
● The term "threading" refers to the process of
aligning the target sequence onto the
structures in the database, searching for the
best fit or match.
Fold Recognition:
● Fold recognition, also known as
protein fold or structure prediction,
involves identifying the structural fold
or topology of a protein.
● Unlike threading, fold recognition
methods don't necessarily rely on a
fixed database of known structures.

6. History
1980s - Early Concepts:
● The foundations of protein threading can be linked to the early years
of structural bioinformatics when researchers began exploring
methods to predict protein structures computationally.
1990s - Threading Algorithms Emerge:
● In the early 1990s, threading algorithms started to gain prominence.
These algorithms were designed to search for the best fit or alignment of a
target protein sequence onto the structures in a protein structure
database.

7. Principle
Sequence-Structure Compatibility:
● Protein threading is based on the assumption that the native structure of a
protein is related to its amino acid sequence. The method aims to find the
best alignment or threading of the target sequence onto known protein
structures.
Template-Based Approach:
● Unlike homology modeling, where a close structural homolog is used as a
template, protein threading does not necessarily rely on a one-to-one match.
Statistical Potentials and Machine Learning:
● Protein threading methods often use statistical potentials or machine
learning techniques to improve the accuracy of scoring functions.

8. Requirement
● Query sequence
● Library of core fold template
● Objective Function(evaluate any particular placement
of sequence in a core template)
● Method of searching over space of alignment
between sequence and each core of template
● Method of choosing the best template given
alignment

9. Workflow

10. Sequence selection
Sequence selection in the context of protein threading refers to the process of choosing a suitable target protein sequence
for structure prediction.
Fold Library
A fold library, in the context of protein structure prediction, refers to a collection or database of representative protein folds
or structural motifs. These libraries serve as valuable resources for computational methods such as protein threading and
fold recognition

12. Threading
● Threading (also known as fold recognition or protein threading) is a technique used to predict
the three-dimensional structure of a protein based on its amino acid sequence.
● This is important because knowing the structure of a protein helps in understanding its
function, interactions with other molecules, and can be crucial for drug design and other
applications.
● The threading method involves aligning the sequence of the target protein with known protein
structures (templates) to predict the spatial arrangement of its amino acids. This process helps to
identify potential structural similarities and infer the likely structure of the target protein.

14. Optimization
Protein Structure Prediction Optimization:
● Threading and Homology Modeling: As mentioned earlier, threading methods and homology modeling are used to
predict the three-dimensional structure of proteins.
● Optimization in these methods involves improving accuracy and efficiency, refining the energy functions used, and
incorporating more accurate templates for modeling.
In protein engineering, rational design involves modifying the amino acid sequence of a protein to
enhance its properties or function. Optimization in this context aims to improve the protein stability,
solubility, catalytic activity, or binding affinity.

15. Energy function
, an energy function is a mathematical model used to assess the compatibility of a protein sequence with a
given three-dimensional protein structure template. The energy function aims to quantify the fitness or
similarity between the sequence of the target protein and the structural features of the template. A lower
energy score indicates a better fit.

16. Solvent Accessibility
● Solvent accessibility refers to the extent to which a particular region of a protein structure is exposed or accessible to
the surrounding solvent molecules, typically water.
● This concept is crucial in understanding the structure and function of proteins.
● Solvent accessibility information provides insights into the local environment of amino acid residues within a protein,
influencing factors such as interactions with other molecules, stability, and the likelihood of being involved in binding
sites
Proteins are composed of amino acid residues, and these residues can be classified based on their solvent
accessibility:
Buried Residues: These are amino acid residues that are shielded from the solvent and located in the
interior of the protein. Buried residues often contribute to the protein's core structure and stability.
Exposed Residues: These residues are located on the surface of the protein and are directly accessible to
the solvent. Exposed residues are more likely to interact with other molecules, such as other proteins, small
ligands, or water molecules.
●

17. Branch and bound

18. How to Build Score Function ?

19. REFERENCES
● "Protein threading by PROSPECT: A prediction server and computational toolbox for structural genomics",Authors: Y.
Xu, M. Madhavan, l. Shetty,. Li,Published in Bioinformatics, 2008
○
● GenTHREADER: an efficient and reliable protein fold recognition method for genomic sequences",Authors: O. S.
Raghava, G. Barton,Published in Journal of Molecular Biology, 2001.
● https://www.slideshare.net/mohammedmuzammil31/threading-and-homology-modelling-methods