In silico Structure Prediction

of Polymers-
Molecular Modeling
 Polymer

Poly mer
many repeat unit (building blocks)

repeat repeat repeat

unit unit unit
H H H H H H H H H H H H H H H H H H
C C C C C C C C C C C C C C C C C C
H H H H H H H Cl H Cl H Cl H CH3 H CH3 H CH3
Polyethylene (PE) Poly(vinyl chloride) (PVC) Polypropylene (PP)

Carbon chain
2
backbone
 Polymer Structure

o Linear

o Branched

o Crosslinked
Structure Prediction
Molecular modeling
Hierarchy of Models
Time
Quantitative Structure/Property
year Relationships (QSPR) &
Theory

min.
Macroscopic
Plant
ms Process
Fab
Continuum
ns CFD
Mesoscale Mechanical
Kinetic
10-12 s Emag

Molecular
Molecular Dynamics
10-15 s Monte Carlo
Quantum Distance
1A 10A 100A 1µm 1cm km
 Mathematical Models

o Ab Initio

o Semi empirical

o Molecular Dynamics
Quantum Mechanics- ab initio
method
o  Uses well known ab initio (from the
first principles) physical constants:
- Velocity of light
- Values of masses and charges of nuclear
particles
- Differential equations
To calculate molecular properties and
geometries
Quantum Mechanics
Schrodinger wave equation
Hψ=Eψ
Approximations

o  The Born-Oppenheimer

approximation (relates
energy to geometry)

o  Hartree-Fock approximation

 Pros & Cons
+++++
Predict structure of-
o  Unsynthesized species
o  difficult (or impossible) to isolate

-Ve
o  Very large calculations
o  Time consuming
Semiempirical Methods

o Several approximations are

used to simplify the
calculations

o Some electron interactions

are ignored
Molecular mechanics

Force Field Theory

o  classical Newtonian physics

o  experimentally derived parameters

o  calculate geometry as a function of steric energy

Protein structure
prediction
Protein Structure
Primary Structure
Ramachandran Plot
Protein Structure
Prediction
Experimental methods
Molecular modeling methods
 Ab-initio Methods

Accurate but time

Comparative modelling of protein
structure
PDB
scan
align

… KDHPFGFAVPTKNPDGTMNLMNWECAIP …
KDPPAGIGAPQDN----QNIMLWNAVIP
** * * * * * * * **

build initial model construct non-conserved

side chains and main chains

refine
Homology Modeling
Homology
Basic steps in Homology
Modeling
o  Database searching

o  Alignment (Pairwise/ Multiple)

o  Model building

o  Model refinement

Identify Homologues in
PDB
Database Search
Alignment
Specific Regions
Structurally Conserved Regions
Structurally Variable
Regions
Generate Core Coordinates
 Model Building

o Replace SVR (Loops)

o Add Side Chains
o Energy Minimization
o Geometry Optimization
Replace SVR (Loops)
Add Side Chains
Energy Minimization
Geometry Optimization
Model Validation
Structure Validation
Example of modelling by Swiss
model
Simple Steps to Build a Protein(Silk
Fibroin) Model
Step1: In your web browser open a link: https://www.ncbi.nlm.nih.gov

A webpage like this will open

Step2: Select Protein from the drop-down menu

Step3: Search for “silk fibroin” in the search box

 Step5: Now click on the FASTA
Step4: Select the first option option to retrieve the amino acid
of the search result
sequence
Step6: Copy the FASTA Step7: Open this link on new tab
sequence & open a new tab in & click on Start Modelling :
the browser https://swissmodel.expasy.org
Step8: Paste the FASTA sequence on the highlighted box & click on
Build Model option

Model result page will

take few seconds to
minutes to build the
model
 The Result Page shows the Protein
Model(right) &
Matching models (left)

Matching
Models