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Lecture 13

This document discusses protein 3D structure prediction and the HP lattice model folding algorithm. It begins with an outline of protein 3D structure and folding algorithms. It then discusses tertiary protein structure, how experimental and computational methods are used to determine 3D structure, and the protein databank. It also describes the protein folding problem and introduces the HP lattice model as a simplified model to study protein folding by restricting conformations to a lattice. The document provides examples of applying the HP lattice model to protein sequences.

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Dishant kumar yadav mhakhariya
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38 views

Lecture 13

This document discusses protein 3D structure prediction and the HP lattice model folding algorithm. It begins with an outline of protein 3D structure and folding algorithms. It then discusses tertiary protein structure, how experimental and computational methods are used to determine 3D structure, and the protein databank. It also describes the protein folding problem and introduces the HP lattice model as a simplified model to study protein folding by restricting conformations to a lattice. The document provides examples of applying the HP lattice model to protein sequences.

Uploaded by

Dishant kumar yadav mhakhariya
Copyright
© © All Rights Reserved
Available Formats
Download as PDF, TXT or read online on Scribd
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Protein 3D structure and Protein Folding Prediction

Manu Madhavan

Lecture 13

Manu Madhavan ISC 211 Lecture 13 1 / 17


Outline

Protein 3D strucutre
Folding algorithm- HP lattice model
Refer: chapter 7 of Krane & Raymer [Kra02]

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Tertiary Structure

Sequence → Structure rightarrow Function


Secondary strucutre interact with each other and give more energy
favoring conformations- 3D structures
Tertiary structures give orientation, exact location of each atom in
the cartesian coordinate system
It contains complete information of the atomic structure

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How to get 3D structure

Experimental Methods
X-ray crystallography
Protein purification
Crystallization
Crystal mounting
Data Collection as electron density map
NMR spectrography
Computational methods- ML, HPC based algorithms

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Tertiary Structure Database- PDB

Demo on PDB
use 2LZM protein as an example

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Protein Folding Problem

Prediction of secondary and 3D structure from a polypeptide chain


Analysing the driving forces of protein folding such as electrostatic
forces, hydrogen bonds, van der Wall forces etc
Intractable problem- it can take large number of conformations..
identifying the most favorable one is challengeing
search space is very large- brute force search is not practical
suppose we have 6 possible structures, a sequence of 100 amino acids
take 61 00 possible structures

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Lattice Model

Instead of allowing all physically possible conformations, the


α-carbons are restricted to positions lying on 2D/3d grid (called a
lattice)
This will reduce the size of search space
Most studied lattice model is H-P lattice model

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H-P Lattice Model

Hydrophobic-Polar lattice model


For 20 amino acids we have a search space of 21 00
We abstract the amino acids into two classes- hydrophobic and polar
This reduce search space in the order of 2

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H-P Lattice Model

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H-P Lattice Model- Example

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H-P Lattice Model- Example

Consider the sequence: HPHPHP

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H-P Lattice Model- Example

Manu Madhavan ISC 211 Lecture 13 13 / 17


H-P Lattice Model- Example

Consider the sequence: PHPPHP

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H-P Lattice Model- Example

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H-P Lattice Model- Example

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References I

Dan E Krane, Fundamental concepts of bioinformatics, Pearson Education India,


2002.

Manu Madhavan ISC 211 Lecture 13 17 / 17

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