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Protein Structure Modelling

There are several methods for protein structure modelling including experimental methods like X-ray crystallography and NMR, as well as computational methods like comparative modelling, threading, and ab initio prediction. Comparative modelling predicts protein structure based on evolutionary relationships, using structures of related proteins as templates. Threading matches protein sequences to known protein folds in a structure database. Ab initio prediction tries to predict structure from sequence alone using scoring functions and search methods, but currently cannot reliably predict native folds. The Chou-Fasman algorithm is a statistical approach that uses amino acid preferences and positional frequencies to predict secondary structure elements like alpha helices and beta sheets.

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Apoorva J
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137 views3 pages

Protein Structure Modelling

There are several methods for protein structure modelling including experimental methods like X-ray crystallography and NMR, as well as computational methods like comparative modelling, threading, and ab initio prediction. Comparative modelling predicts protein structure based on evolutionary relationships, using structures of related proteins as templates. Threading matches protein sequences to known protein folds in a structure database. Ab initio prediction tries to predict structure from sequence alone using scoring functions and search methods, but currently cannot reliably predict native folds. The Chou-Fasman algorithm is a statistical approach that uses amino acid preferences and positional frequencies to predict secondary structure elements like alpha helices and beta sheets.

Uploaded by

Apoorva J
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PROTEIN STRUCTURE MODELLING

Experimental Methods - X-Ray Diffraction studies - NMR Analyses Computational Methods - Comparative Modelling - Threading (Fold Recognition) - Ab Initio Prediction (DENOVO METHOD)

COMPARATIVE MODELLING PRINCIPLE: Evolutionarily related proteins with similar sequences, as measured by percentage of identical residues at each position based on alignments, have similar structures The similarity is high in core regions composed of secondary structure elements such as alpha helices and beta sheets. How is it performed? - First an alignment is performed between sequence for which structure has been determined (reference) with the sequence whose structure is to be determined (target) - This alignment helps construct an initial model by copying over some main chain and side chain coordinates from reference based on equivalent residues in reference that does not correspond to an equivalent residue in alignment. - Side chains must be built for residues in reference that does not correspond to an identity in the alignment, and for residues where side chain conformation is known to vary from reference - Main chains must be built in regions of insertions/deletions (INDELs) THREADING It uses a database of known 3D structures to match sequence without known structure with protein folds.

This is accomplished by the aid of a scoring function that assesses the fit of a sequence to a given fold. How is it performed? It compares a target sequence against a library of structural templates, producing a list of scores The scores are then ranked and the fold with the best score is assumed to be the one adopted by the sequence AB INITIO PREDICTION It involves two components: a) Devising a scoring function that can distinguish between correct and incorrect structures (non-native) accurately b) Devising a search method to explore the 3D space Currently there are no reliable and general scoring functions that can always drive a search to a native fold. ALGORITHMS FOR PREDICTION OF SECONDARY STRUCTURE There exist many algorithms for prediction of secondary structure but the one we will be covering here is Chou-Fasman algorithm CHOU-FASMAN ALGORITHM It is one of the most widely used predictive schemes. It is a straight forward statistical approach to predicting secondary structure. Each amino acid is assigned 3 conformational parameters P(a), P(b) and P(turn). This corresponds to the preference of the amino acid to be found in a helix, sheet or turn. They are also assigned four positional frequencies f(j), f(j+1), f(j+2), f(j+3). This corresponds to the frequency with which the amino acid was observed in first, second, third and fourth position of a hairpin turn. Identifying alpha helices: Find regions with 4 amino acids each with P(a)>100 that are present in a contiguous fashion. For each region, extend it on both sides (direction) until a set of four contiguous residues with P(a)<100 is encountered.

For each residue in the extended region, note P(a) and P(b). Calculate P(a) and P(b). If region is >5 residues and sigma P(a) >P(b) then region is predicted to be an alpha helix. Identifying beta sheets: Same as before, except look for P(b)>100 and predict it as beta sheet if P(b)> P(a). If any of the helices or sheets assigned, overlap each other, then, the overlapping region is preferred to be a sheet if P(b)>P(a) and helix if P(a) >P(b). Identifying beta turns: For each residue j calculate P(t) as follows: P(t)=f(j)*f(j+1)*f(j+2)*f(j+3) If: a) P(t) >0.000075 b) P(turn)>100 in the tetra peptide bond c) The averages for the tetra peptide obey the inequality P(helix)<P(turn)>P(sheet) then a beta turn is predicted.

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