Protein 3D structure and Protein Folding Prediction

Manu Madhavan

Lecture 13

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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

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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.

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