Unit-IV

Protein Structure, Synthesis of Drug molecules, Drug design

and Discovery

1. Explain briefly about proteins. Give the classification of aminoacids

(Or)
How proteins are essential to a human body and give its importance.
(Or)
What are essential and non-essential aminoacids.
Ans: Proteins are made up of hundreds or thousands of smaller units called amino acids,
which are attached to one another in long chains. There are 20 different types of amino acids
that can be combined to make a protein.
Amino acid, any of a group of organic molecules that consist of a basic amino group
(―NH2), an acidic carboxyl group (―COOH), and an organic R group (or side chain) that is
unique to each amino acid.
Roughly 500 amino acids have been identified in nature, but just 20 amino acids make up the
proteins found in the human body.

Classification of aminoacids:
All The 20 amino acids are classified into two different amino acid groups. Essential amino
acids and Non-essential amino acids.
1.Essential amino acids:
A. Branched-chain amino acids (BCAAs) are a group of three amino acids (valine,
leucine and isoleucine) that have a molecular structure with a branch. BCAAs are plentiful in
muscle proteins, stimulate muscle growth in the body and provide energy during exercise.(for
better sports performance)
B. Lysine is one of the most commonly mentioned essential amino acids. Foods such as
bread and rice tend to be low in lysine.(for nutrition improvement)
C. Threonine: An essential amino acid that is used to make the active site of enzymes.
D. Phenylalanine: An essential amino acid that is used to make many types of useful
amines.
E. Methionine: An essential amino acid that is used to make many different substances
needed in the body.
F. Histidine: An essential amino acid that is used to make histamine.
G. Tryptophan: An essential amino acid used to make many types of useful amines.
2.Non-essential aminoacids:
A. Glutamine is one of the most common amino acids in the body. Glutamine is used to
produce energy for the gastrointestinal tract. Glutamine promotes the metabolization of
alcohol to protect the liver.(for hangover)
B. Aspartate is one of the amino acids that is most usable for energy. It is poitioned
closely to the tricarboxylic acid (TCA) cycle in the body that produces energy. (for delicious
taste)
C. Glutamate: Inside the body, glutamate is utilized as an important source of essential
amino acids.(for delicious taste)
D. Arginine: Nitric oxide that opens up the veins is made from arginine. Arginine is a
useful amino acid for removing excess ammonia from the body. Arginine increases
immunity.
E. Alanine supports function of the liver. Alanine is used to make glucose that are
needed by the body. Alanine improves the metabolization of alcohol.
F. Proline is one of the amino acids contained in collagen that makes up skin tissue.
Proline is one of the most important amino acids to the natural moisturizing factor (NMF)
that keeps skin moist.
G. Cysteine reduces the amount of black melanin pigmentation made. Cysteine is
plentiful in head hair and body hair. Cysteine increases the amount of yellow melanin made
instead of black melanin.
H. Asparagine: An amino acid that was discovered from asparagus. Both asparagine and
Aspartate are positioned close to the tricarboxylic acid (TCA) cycle that produces energy.
I. Serine: An amino acid used to make phospholipids and glyceric acid.
J. Glycine is plentiful in the body. It acts as a transmitter in the central nervous system
and helps regulate body functions such as locomotion and sensory perception. Glycine makes
up one-third of collagen.
K. Tyrosine is used to make many types of useful amines. Tyrosine is grouped as an
aromatic amino acid together with phenylalanine and tryptophan.

2. Explain briefly about the structure of protein with its classification.

(Or)
What is Protein structure. Describe the complete structure of protein with classification
.
Ans: Protein structure is the three-dimensional arrangement of atoms in an amino acid-chain
molecule. The complete structure of a protein can be described at four different levels of
complexity namely primary, secondary, tertiary, and quaternary structure.The protein
structure has multiple amino acids which are linked together by peptide bonds, thereby
forming a long chain. Peptide bonds are formed by a biochemical reaction that extracts a
water molecule as it joins the amino group of one amino acid to the carboxyl group of a
neighboring amino acid.

1)Primary structure: is simply the sequence of amino acids in a polypeptide chain.The

linear sequence of amino acids within a protein is considered the primary structure of the
protein.
For example, the pancreatic hormone insulin has two polypeptide chains, A and B.

2)Secondary structure: refers to local folded structures that form within a polypeptide due
to interactions between atoms of the backbone. (The backbone just refers to the polypeptide
chain apart from the R groups – so all we mean here is that secondary structure does not
involve R group atoms.)
The most common types of secondary structures are the α helix and the β pleated sheet. Both
structures are held in shape by hydrogen bonds, which form between the carbonyl O of one
amino acid and the amino H of another.
i)In an α helix, the carbonyl (C=O) of one amino acid is hydrogen bonded to the amino H (N-
H) of an amino acid that is four down the chain. (E.g., the carbonyl of amino acid 1 would
form a hydrogen bond to the N-H of amino acid 5.) This pattern of bonding pulls the
polypeptide chain into a helical structure that resembles a curled ribbon, with each turn of the
helix containing 3.6 amino acids. The R groups of the amino acids stick outward from the α
helix, where they are free to interact.
ii)In a β pleated sheet, two or more segments of a polypeptide chain line up next to each
other, forming a sheet-like structure held together by hydrogen bonds. The hydrogen bonds
form between carbonyl and amino groups of backbone, while the R groups extend above and
below the plane of the sheet. The strands of a β pleated sheet may be parallel, pointing in the
same direction (meaning that their N- and C-termini match up), or antiparallel, pointing in
opposite directions (meaning that the N-terminus of one strand is positioned next to the C-
terminus of the other).
3)Tertiary Structure: The tertiary structure is formed by many different bonds between R
groups that make up the side chains, that make the strand of molecule bend and loop around
in a more complicated three dimensional form.
Interactions between polar, nonpolar, acidic, and basic R group within the polypeptide chain
create the complex three-dimensional tertiary structure of a protein. When protein folding
takes place in the aqueous environment of the body, the hydrophobic R groups of nonpolar
amino acids mostly lie in the interior of the protein, while the hydrophilic R groups lie
mostly on the outside. Cysteine side chains form disulfide linkages in the presence of
oxygen, the only covalent bond forming during protein folding. All of these interactions,
weak and strong, determine the final three-dimensional shape of the protein. When a protein
loses its three-dimensional shape, it will no longer be functional.
4)Quaternary structure: Many proteins are made up of a single polypeptide chain and have
only three levels of structure (primary, secondary and tertiary). However, some proteins are
made up of multiple polypeptide chains, also known as subunits. When these subunits come
together, they give the protein its quaternary structure.
Ex: haemoglobin, DNA polymerase, and ion channels.

3. What are protein databases used for?

Ans: Protein Databases:
 As biology has increasingly turned into a data-rich science, the need for
storing and communicating large datasets has grown tremendously.
 The obvious examples are the nucleotide sequences, the protein sequences,
and the 3D structural data produced by X-ray crystallography and
macromolecular NMR.
 The biological information of proteins is available as sequences and structures.
Sequences are represented in a single dimension whereas the structure contains
the three-dimensional data of sequences.
 A biological database is a collection of data that is organized so that its
contents can easily be accessed, managed, and updated.
 A protein database is one or more datasets about proteins, which could include
a protein’s amino acid sequence, conformation, structure, and features such as
active sites. 
 Protein databases are compiled by the translation of DNA sequences from
different gene databases and include structural information. They are an
important resource because proteins mediate most biological functions.

4. Write the importance of Protein Databases.

Ans: Importance of Protein Databases:
Huge amounts of data for protein structures, functions, and particularly sequences are
being generated. Searching databases are often the first step in the study of a new
protein. It has the following uses:
1. Comparison between proteins or between protein families provides
information about the relationship between proteins within a genome or across
 different species and hence offers much more information that can be obtained
by studying only an isolated protein.
2. Secondary databases derived from experimental databases are also widely
available. These databases reorganize and annotate the data or provide
predictions.
3. The use of multiple databases often helps researchers understand the structure
and function of a protein.

5.Write about primary and secondary databases of Protein.

Ans: Primary databases of protein:
The PRIMARY databases hold the experimentally determined protein sequences
inferred from the conceptual translation of the nucleotide sequences. This, of course,
is not experimentally derived information, but has arisen as a result of interpretation
of the nucleotide sequence information and consequently must be treated as
potentially containing misinterpreted information. There is a number of primary
protein sequence databases and each requires some specific consideration.
a. Protein Information Resource (PIR) – Protein Sequence Database (PIR-PSD):
 The PIR-PSD is a collaborative endeavor between the PIR, the MIPS (Munich
Information Centre for Protein Sequences, Germany) and the JIPID (Japan
International Protein Information Database, Japan).
 The PIR-PSD is now a comprehensive, non-redundant, expertly annotated,
object-relational DBMS.
 A unique characteristic of the PIR-PSD is its classification of protein
sequences based on the superfamily concept.
 The sequence in PIR-PSD is also classified based on homology domain and
sequence motifs.
 Homology domains may correspond to evolutionary building blocks, while
sequence motifs represent functional sites or conserved regions.
 The classification approach allows a more complete understanding of
sequence function-structure relationship.
b. SWISS-PROT
 The other well known and extensively used protein database is SWISS-PROT.
Like the PIR-PSD, this curated proteins sequence database also provides a
high level of annotation.
 The data in each entry can be considered separately as core data and
annotation.
 The core data consists of the sequences entered in common single letter amino
acid code, and the related references and bibliography. The taxonomy of the
organism from which the sequence was obtained also forms part of this core
information.
 The annotation contains information on the function or functions of the
protein, post-translational modification such as phosphorylation, acetylation,
etc., functional and structural domains and sites, such as calcium binding
regions, ATP-binding sites, zinc fingers, etc., known secondary structural
features as for examples alpha helix, beta sheet, etc., the quaternary structure
of the protein, similarities to other protein if any, and diseases that may arise
due to different authors publishing different sequences for the same protein,
or due to mutations in different strains of an described as part of the
annotation.
c. TrEMBL (for Translated EMBL) :
 It is a computer-annotated protein sequence database that is released as a
supplement to SWISS-PROT. It contains the translation of all coding
sequences present in the EMBL Nucleotide database, which have not been
fully annotated. Thus it may contain the sequence of proteins that are never
expressed and never actually identified in the organisms.
d. Protein Databank (PDB):
 PDB is a primary protein structure database. It is a crystallographic database
for the three-dimensional structure of large biological molecules, such as
proteins.
 In spite of the name, PDB archive the three-dimensional structures of not only
proteins but also all biologically important molecules, such as nucleic acid
fragments, RNA molecules, large peptides such as antibiotic gramicidin and
complexes of protein and nucleic acids.
 The database holds data derived from mainly three sources: Structure
determined by X-ray crystallography, NMR experiments, and molecular
modeling.

Secondary databases of protein:

The secondary databases are so termed because they contain the results of analysis
of the sequences held in primary databases. Many secondary protein
databases are the result of looking for features that relate different proteins.
Some commonly used secondary databases of sequence and structure are as
follows:

a. PROSITE: 
 A set of databases collects together patterns found in protein sequences rather
than the complete sequences. PROSITE is one such pattern database.
 The protein motif and pattern are encoded as “regular expressions”.
 The information corresponding to each entry in PROSITE is of the two forms
– the patterns and the related descriptive text.
b. PRINTS:
 In the PRINTS database, the protein sequence patterns are stored as
‘fingerprints’. A fingerprint is a set of motifs or patterns rather than a single
one.
 The information contained in the PRINT entry may be divided into three
sections. In addition to entry name, accession number and number of motifs,
the first section contains cross-links to other databases that have more
information about the characterized family.
 The second section provides a table showing how many of the motifs that
make up the fingerprint occurs in the how many of the sequences in that
family.
 The last section of the entry contains the actual fingerprints that are stored as
multiple aligned sets of sequences, the alignment is made without gaps.
There is, therefore, one set of aligned sequences for each motif.
c. MHCPep:
 MHCPep is a database comprising over 13000 peptide sequences known to
bind the Major Histocompatibility Complex of the immune system.
 Each entry in the database contains not only the peptide sequence, which may
be 8 to 10 amino acid long but in addition has information on the specific
 MHC molecules to which it binds, the experimental method used to assay the
peptide, the degree of activity and the binding affinity observed , the source
protein that, when broken down gave rise to this peptide along with other, the
positions along the peptide where it anchors on the MHC molecules and
references and cross-links to other information.
d. Pfam
 Pfam contains the profiles used using Hidden Markov models.
 HMMs build the model of the pattern as a series of the match, substitute, insert
or delete states, with scores assigned for alignment to go from one state to
another.
 Each family or pattern defined in the Pfam consists of the four elements. The
first is the annotation, which has the information on the source to make the
entry, the method used and some numbers that serve as figures of merit.
 The second is the seed alignment that is used to bootstrap the rest of the
sequences into the multiple alignments and then the family.
 The third is the HMM profile.
 The fourth element is the complete alignment of all the sequences identified in
that family.

6. What are the various protein structure prediction analysis tools available and
write flow diagram in prection?

Software
Program Use or Function URL (Reference)
PHD A method for sequence analysis and http://www.embl-heidelberg.de/
structure prediction predictprotein/predictprotein.html Rost 1996.

APSSP2 Advanced protein secondary structure http://www.imtech.res.in/raghava/apssp2/

prediction server.

PsiPred Allows prediction of protein secondary http://bioinf.cs.ucl.ac.uk/psipred/ Mcguffin et

structure, topology of transmembrane al. 2000.
domains and fold prediction.

JPRED A consensus method for predicting http://www.compbio.dundee.ac.uk/∼www-

protein secondary structure. jpred/ (Cuff et al. 1998)

GEN03D Automatic modeling of protein three- http://geno3d-pbil.ibcp.fr/ Combet et al. 2002.

dimensional structures.

CPHMODELS Fold recognition/homology modeling. http://www.cbs.dtu.dk/services/CPHmodels/

7. What is proteing structue alignment? Write the importance of alignment and
explain the process with any one alinment tool.
Ans: Structure alignment is a process wherein molecular structures of two or more
biopolymers (e.g., proteins or large ribonucleic acids) are compared to establish
equivalences in their three-dimensional shapes.
Structural alignment is a valuable tool for the comparison of proteins with low
sequence similarity, where evolutionary relationships between proteins cannot be
easily detected by standard sequence alignment techniques. Structural alignments can
compare two sequences or multiple sequences.
The objective of structure alignment is identification of the maximal set of
corresponding pairs of amino acid residues that gives a good structural match when
the structures are overlaid, i.e., superposed. Only the positions of the protein’s
backbone C-alpha atoms and/or location of secondary structural elements are
considered in this alignment. The amino residue type is ignored.
iPBA is a tool for protein structure comparison using sequence alignment strategies.
Steps to Aligning multiple protein sequences:
1.Click on the Align link in the header bar to align two or more protein sequences
with the Clustal Omega program.
2.Enter either protein sequences in FASTA format or UniProt identifiers into the form
field.
3.Click the 'Run Align' button.
8. What are the challenges in drug discovery? Or What are the areas influence
drug discovery?
Ans: There are several approaches to discover new drugs. They range from molecular
biology to combinatorial chemistry. Following are some of the approaches-
1. The influence of Molecular biology: The discipline of molecular biology has become
increasingly important in recent times for the process of drug discovery.
The impact of molecular biology across the whole process of drug discovery and
development, including (i) the identification and validation of new drug targets, (ii) the
development of molecular screens to find new candidate drugs, and (iii) the generation of
safety data and competences leading to enhanced clinical efficacy.
Molecular biology will play an even more vital role in the generation of future therapies.
2. High-throughout Screening (HTS): It is the use of automated equipment to rapidly test
thousands to millions of samples for biological activity at the model organism, cellular,
pathway, or molecular level.
HTS is an experimental process in which 103–106 small molecule compounds of known
structure are screened in parallel.
HTS is commonly used in pharmaceutical and biotechnology companies to identify
compounds (called hits) with pharmacological or biological activity.
3. Combinatorial chemistry: Combinatorial chemistry comprises chemical synthetic methods
that make it possible to prepare a large number (tens to thousands or even millions) of
compounds in a single process. These compound libraries can be made as mixtures, sets of
individual compounds or chemical structures generated by computer software.
4. Pharmacogenomics: Pharmacogenomics is the study of how genes affect a person’s
response to drugs. This relatively new field combines pharmacology (the science of drugs)
and genomics (the study of genes and their functions) to develop effective, safe medications
and doses that will be tailored to a person’s genetic makeup.
Benefits: More powerful medicines, Better and safer drugs the first time, More accurate
methods of determining appropriate drug dosages, Advanced screening for disease, Better
vaccines, Improvements in the drug discovery and approval process, Decrease in the overall
cost of health care.
5, Pharmacogenetics: Pharmacogenetics is the study of how people respond differently to
drug therapy based upon their genetic makeup or genes.
(In general pharmacogenetics usually refers to how variation in one single gene influences
the response to a single drug. Pharmacogenomics is a broader term, which studies how all of
the genes (the genome) can influence responses to drugs. However, these terms are often
used interchangeably.)
5. Pharmacogenetic technology: Pharmacogenetics make extensive use of the automated
tools for gene and protein sequencing. The determination of nucleotide and amino acid
sequence of genes and proteins is used for analysis of genetic differences at an individual
level. There are two main strategies used in screening for polymorphism in an individual:
Phenotyping and Genotyping.

9. Define drug discovery and explain the parameters of drug discovery.

Ans: Drug discovery is the process by which new candidate medications are discovered in
the context of drug discovery and design. There are five major parameters of drug discovery::
1. Target Identification
2. Target Validation
3. Lead identification
4. Lead Optimization
5. Preclinical pharmacology and Toxicology
1. Target Identification: is to identifying the function of a possible therapeutic target
(gene/protein) and its role in the disease.
Conventional drug discovery process focusses on a known pathological phenomenon and
then develop a therapy to combat it. The process of therapy is chemistry - based, I.e you need
to produce compounds for screening. The approaches of identifying targets include protein
expression, protein biochemistry, structure function studies, study of biochemical pathway
etc.
There are now several other methods to identify specific molecular targets like high
throughput sequencing analysis, potential cloning, generation of cDNA(complimentaryDNA)
libraries with ESTs(Expressed Sequence Targets) and database mining by sequence
homology. These high-throughput technologies and the knowledge of the human genome
map generate a very large number of prospective targets. It is impotant to determine whether
these novel targets are actually relevent to the physiology of the disease.
2. Target Validation: This process involves the application of a range of techniques that aim
to “demonstrate that drug effects on the target can provide a therapeutic benefit with an
acceptable safety window”.
Targeted gene disruption (TGD) is a term thet refers to several different methods of target
validation. TGD related to the production of knockout or transgenic animals to study the
effect of removing a particular gene coding for the putative(commonly accepted/supposed)
molecular target.
3. Lead identification: A Lead is defined as a compound (usually a small organic molecule)
that demonstrates a desired biological acivity on a validated molecular target. To be termed
as a Lead, the compound must exceed a specific potency threshold against the target.
The compounds used as potential leads can be from many sources. The most impotant source
of leads is “libraries” of molecule, e.g natural product libraries, peptide libraries,
carbohydrate libraries etc. “Virtual libraries” can be created by using combinatorial
chemistry.
 Each lead must be screened by an appropriate assay against the molecular target. This
may take any amount of time, maybe, as long as several years as the failure rate is very
high.
4. Lead Optimization: Lead optimization is the process by which a drug candidate is
designed after an initial lead compound is identified.
Lead optimization aims at enhancing the most promising compounds to improve
effectiveness, diminish toxicity, or increase absorption.
5. Preclinical pharmacology and Toxicology: Preclinical studies refer to the testing of a
drug, procedure or other medical treatment in animals before trials may be carried out in
humans. During preclinical drug development, the drug's toxic and pharmacological effects
need to be evaluated through in vitro and in vivo laboratory animal testing.
Toxicity testing of new compounds is essential for drug development process. The preclinical
toxicity testing on various biological systems reveals the species-, organ- and dose- specific
toxic effects of an investigational product.

10. What is the role of genomic and proteomic technologies in drug discovery?
Ans: Drug discovery is a multi-step process involving target selection, lead identification and
clinical candidate selection before clinical trials. With the rapid advances in structural
biology and computer technology, drug discovery has been enriched by genomic and
proteomic technologies.
Contribution of Genomic technologies;
The following genomic technologies are available-
 Novel DNA sequencing technologies
 DNA chip technology or microarray technology
 Metabolic profiling technologies.
 Drug Discovery strategies
These technologies have created a profound impact on pharmacology, medicine and
diagnostics.
Genomic technologies can be applied to a cell at all biological levels
Biological level Genomic Technologies
1. Genome sequencing Shortgun sequencing
2. Transcriptome: Transcriptional activities DNA microarrays and DNA chip technologies
Of genes
3. Proteomics: Quantification of all proteins Protein chips, mass spectroscopy, 2D gel
Electrophorosis
4. Metabolome: Quantitative monitoring of Mass spectroscopy, liquid chromatography,
Metabolites NMR and gas chromatography
5. Mentification of chemical compounds Screening of target based assays

Genomic technologies: Common applications of proteomics in the drug industry include

target identification and validation, identification of efficacy and toxicity biomarkers from
readily accessible biological fluids, and investigations into mechanisms of drug action or
toxicity.
These technologies include chemical proteomics, structural proteomics, topological
proteomics and computational proteomics.
Chemical proteomics aims at designing chemical probes to target proteins belonging to
enzyme families.
Structural proteomic is a powerful tool to design drugs by determining 3D structures of
protein or protein complexes found in specific cellular organelles.
Topological proteomics aims at characterizing the protein network within a cell.
Computational proteomics provides information about 3D protein structures. Good
resources are available in PDB (https://www.rcsb.org/pdb/) and 3D genomics
(https://www.sbg.bio.ic.au.uk/3dgenomics)

11. What are the steps involved in drug discovery or Explain about strategies for drug
discovery.
Ans:
1. Target identification strategies:
A. Genetic associations: is when one or more genotypes within a population co-occur with a
phenotypic trait more often than would be expected by chance occurrence.
B. Examining mRNA/Protein levels: The expression level of a gene can be calculated by
measuring the transcribed mRNA (northern blot), the expressed protein (Western Blot), or by
directly staining the protein or mRNA when it is still in the cell.
C. Docking as Drug discovery tool: docking is a method which predicts the preferred
orientation of one molecule to a second when bound to each other to form a stable complex.

2. Target validation strategies:

A. Transgenic animals: Transgenic rats as models for hypertension, Atherosclerosis,
Alzhemer’s disease.
B. Antisense technology: is a new and promising tool for controlling gene expression in a
cell. Currently, it is used to design therapeutic compounds which target specific mRNA
sequences to obstruct the production of certain disease causing proteins.
C. Chemical genomics: is the systematic screening of targeted chemical libraries of small
molecules against individual drug target families (e.g., GPCRs, nuclear receptors, kinases,
proteases, etc.) with the ultimate goal of identification of novel drugs and drug targets.

3. Hit Discovery process:

A, Physiological screening: A tissue based approach and looks for a response more alligned
with the final desired in vivo effect as opposed to targeting one specific molecular
component.
B. High throughput screening: is a drug discovery process that allows automated testing of
large numbers of chemical and/or biological compounds for a specific biological target.
It remove inactive targets at initial stage and accumulate active compounds.

4. Lead Optimization strategies:

A. Absorption/Adsorption strategies: Animal strudies(rats), In situ intestinal models,
intestinal epithelial barrier model.
B. Distribution strategies: Equilibrium dialysis, Ultrafiltration
C. Metabolism strategies: Assessment of metabolic stability, Metabolite characterization
D. Excretion strategies: In vitro models to investigate renal excretion are limited. The
primary in vitro renal excretion model is the isolated perfused rat kidney.
E. Insilico ADME screening: Molecular based modelling and Data based modelling.
5. Prediction of drug safety: In vitro and in vivo methods.
6. Estimation of human starting dose for phase I:
Phase I studies of a new drug are usually the first that involve people. Phase I studies are
done to find the highest dose of the new treatment that can be given safely without causing
severe side effects.
7. Phase of clinical trails.

12. Define Lead. Explain about technologies used to identify lead.

Ans: A Lead is defined as a compound (usually a small organic molecule) that demonstrates
a desired biological acivity on a validated molecular target.

Some of the technologies used in the lead identification are:

 Virtual screening: is part of chemoinformatics. It involves protein-structure-based
compound screening or docking and chemical-similarity search based on small
molecules. VS technologies are used in high throughput docking, homology seaching
and pharmaphore searches of 3D database.
 Chemoinformatics: combines elements of biology and chemistry with mathematics,
statistics and computer sciences. Analysis in chemoinformatics focuses on several types
of large databases available such as micromolecular structures, 3D chemical databases
and compound libraries.
 Paharmacaphore mapping: The pharmacophore search is an approach to identify lead
compounds against a desired target. A parmacophore is the specific 3D arrangement of
functional groups within a molecular framework that are neessary to bind to a
macromolecules and/or an enzyme active site. The identification of a pharmacophore is
an important step in understanding the interaction between a receptor and a ligand.
 Qualitative structure Acivity Relationship(QSAR): Quantitative structure-activity
relationship (QSAR) is a computational modeling method for revealing relationships
between structural properties of chemical compounds and biological activities. Models
derived from training sets can be applied to predicted molecules with higher potency.
 High throughput docking: Docking refers to the ability to position a ligand in the active
or a designated site of a protein and calculate specific binding affinities. Ligand-Protein
docking has evolved so that docking single or multiple small molecules to a receptor site
is now routinely used to identify ligands.
 NMR-based screening: NMR‐based screening refers to the identification of ligands for a
pharmaceutically relevant target protein by the use of NMR spectroscopy. A variety of
nuclear magnetic resonance (NMR) applications have been developed for structure-
based drug discovery (SBDD). NMR provides many advantages over other methods,
such as the ability to directly observe chemical compounds and target biomolecules, and
to be used for ligand-based and protein-based approaches.
 Chemical genetics: Chemical genetics is the study of gene-product function in a cellular
or organismal context using exogenous ligands. In this approach, small molecules that
bind directly to proteins are used to alter protein function, enabling a kinetic analysis of
the in vivo consequences of these changes.

13. Write the structure, synthesis and applications of Aspirin.

Ans:
Structure:

Synthesis:
The reaction that is used for the synthesis is shown below. In this reaction, an excess
of acetic anhydride (C4H6O3) is added to a measured mass of salicylic acid (C 7H6O3)
in the presence of a catalyst, sulfuric acid (H 2SO4). The mixture is heated to form the
acetylsalicylic acid (C9H8O4) and acetic acid (C2H4O2). After the reaction takes place,
water is added to destroy the excess acetic anhydride and cause the product to
crystallize. The aspirin is then collected, purified by recrystallization.

Applications:
It is used to reduce fever and relieve mild to moderate pain from conditions such as
muscle aches, toothaches, common cold, and headaches. It may also be used to reduce
pain and swelling in conditions such as arthritis. Aspirin is known as a salicylate and a
non-steroidal anti-inflammatory drug (NSAID). 

14. Write the structure, synthesis and applications of Paracetamol.

Ans:Structure:
Synthesis:
Take 1 grams of 4-aminophenol into a beaker. Using dropper add 3 mL of acetic anhydride. The
reaction mixture is heated (120°C ) for 15 minutes, stirring continuously. Heating and stirring process
continuous till the reaction mixture become colorless. After 15 minutes take the flask from burner
allow the flask to cool to room temperature. On cooling, crude paracetamol will form in the beaker.
Collect precipitated paracetamol by filtration. After drying take the weight of product ( crude
paracetamol).

Applications:
Paracetamol. Paracetamol is a commonly used medicine that can help treat pain and
reduce a high temperature (fever). It's typically used to relieve mild or moderate pain,
such as headaches, toothache or sprains, and reduce fevers caused by illnesses such as
colds and flu.