PROTEIN

STRUCTURE
ANALYSIS AND
PREDICTION –
SUMMARY &
DISCUSSION
IMPORTANT QUESTIONS IN THIS LECTURE TOPIC

 Why do we need to study protein structure?

 What are the experimental methods to determine the 3D structure of proteins?

 What are the advantages & disadvantages of the 2 main experimental methods?

 Which bioinformatics programs for viewing 3D structures?

 What are the in silico approaches (3 main strategies) to predict protein structures?

 When do you use these approaches and under which conditions?

1. WHY DO WE NEED TO DETERMINE PROTEIN
STRUCTURES?
TIMELINE FOR COVID-19 VACCINE DEVELOPMENT
First cases of COVID-19 New virus, nCoV-2019
reported in Wuhan (later renamed SARS-CoV-
2) identified as etiological
agent for COVID-19
Nov 2019 Jan 7, 2020
First complete viral
genome of SARS-CoV-2
sequenced and deposited
into Virological website for
open access.
Jan 11, 2020
3-D protein structure of Clinical trials for vaccines
spike protein of SARS-CoV- against COVID-19 started
2 solved
Mar 30, 2020 May 2020
Created by : Prof. Dr. Chong Pei Pei
1. WHY WE NEED TO DETERMINE PROTEIN STRUCTURES

 The structure of a protein would determine its _____________________.

 Hence, knowing the structure of proteins can help us in designing ___________ against infections, against cancer
and other diseases.
 Information about the protein structures can allow us to _______________ it and improve its ______________.

 There are _____________ levels of protein structure. The ______________ level of protein structure is the most
important in determining the shape of the protein and how it works.
 How a protein folds into a specific shape is determined by the ______________ and _____________ properties of
the proteins, which are a result of its ______________________ sequence.
2. WHAT ARE THE EXPERIMENTAL METHODS TO
DETERMINE THE 3D STRUCTURE OF PROTEINS?
2. WHAT ARE THE EXPERIMENTAL METHODS TO DETERMINE THE 3D
STRUCTURE OF PROTEINS?

 1. X-ray crystallography

 2. Nuclear Magnetic Resonance

 3. Cryo-Electron Microscopy
X-ray crystallography
 X-ray Crystallography
Steps in structure determination
Protein Nuclear Magnetic Resonance (NMR)
Protein Nuclear Magnetic Resonance (NMR)
Protein Nuclear Magnetic Resonance (NMR)
Protein Nuclear Magnetic Resonance (NMR)
3. WHAT ARE THE ADVANTAGES & DISADVANTAGES
OF THE 2 MAIN EXPERIMENTAL METHODS?
4. WHICH BIOINFORMATICS PROGRAMS FOR
VIEWING 3D STRUCTURES?
Interactive visualization tools for PDB protein structures

Visualization tools are available within PDB and elsewhere.

 Visualizing myoglobin structure 3RGK: Jmol applet

B&FG 3e
Fig. 13.11
Page 607
Jmol is available at
PDB.
 Molecular Modeling Database (MMDB) at NCBI

B&FG 3e
Fig. 13.12 You can study PDB structures from NCBI. MMDB offers
Page 608 tools to analyze protein (and other) structures.
Cn3D: NCBI software for visualizing protein structures

Several display formats are shown

Vector Alignment Search Tool (VAST) at NCBI:
comparison of two or more structures
VAST: NCBI tool to compare two structures
 Swiss PDB Viewer
• It’s a structure viewer for multiple platform
• It is capable of homology modeling
• It is capable of structure visualization and
analysis
• It enables the visualization of crystal
structure of proteins
PDB Viewer Interface
5. WHAT ARE THE IN SILICO APPROACHES (3 MAIN
STRATEGIES) TO PREDICT PROTEIN STRUCTURES?
 Swiss PDB Viewer
• It’s a structure viewer for multiple platform
• It is capable of homology modeling
• It is capable of structure visualization and
analysis
• It enables the visualization of crystal
structure of proteins
 Three main structure prediction strategies

There are three main approaches to protein structure prediction.

1. Homology modeling (comparative modeling). Also known as template-

based modeling. This is most useful when a template (protein of interest)
can be matched (e.g. by BLAST) to proteins of known structure.
2. Fold recognition (threading). A target sequence lacks identifiable
sequence matches and yet may have folds in common with proteins of
known structure.
3. Ab initio prediction (template-free modeling). Assumes: (1) all the
information about the structure of a protein is contained in its amino acid
sequence; and (2) a globular protein folds into the structure with the
lowest free energy.
 Three main structure prediction strategies

B&FG 3e
Fig. 13.20
Page 618
 Structure prediction techniques as a function of
sequence identity

B&FG 3e
Fig. 13.21
Page 620
Websites for structure prediction by comparative
modeling, and for quality assessment