Drug 

Development: Advancements in virtual
Screening and Design​
Chandani Singh
M.SC. 4th sem
Supervision of Dr. Anjani Kumar Tiwari

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1 : INTRODUCTION : DRUG DEVELOPMENT :

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1INTRODUCTION:
1.1 DOCKING AND ROLL  IN DRUG DEVELOPMENT
 Docking is a computational technique used in drug discovery to predict how a
small molecule (the ligand) will bind to a target protein (the receptor) in order to form a
stable complex. 
 The docking process involves generating a large number of possible ligand conformations
and orientations, and then scoring them based on their predicted binding energy or affinity.
​
 The ligand is then ranked according to its score, and the top candidates are selected for
further experimental validation​
 Key and lock method

 
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1.2Docking plays an important role in drug​

 identifying potential ligands that are predicted to bind strongly

to the target protein, researchers can
prioritize compounds for further testing and optimization.
Docking is also useful for
understanding the molecular interactions that occur between the
ligand and receptor, which can help guide the design of new compounds
with improved binding properties.​

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Receptor(protein) Interaction of ligand with receptor

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MEHODOLOGY
DOCKING

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 • The method works by comparing the interactions
between the ligand and protein in the
docked complex to those observed in a set
of experimentally determined complexes.

•  The energy contributions of each interaction are

2.2The Hyde scoring process in docking then weighted according to their importance
involves in reproducing the experimental binding affinity,
resulting in a final score that reflects the
predicted binding strength of the ligand.​

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2.3ADME data collection methodology.​

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3.0:MOLECULE WE ANALYS
3.1:Structure and group substituted
Series I R1 R2
​
1 OH H
2 CH2COR H
R1 N
3 I H
4 H NO2 R2

5 H CHO HN

6 H COOH
7 CH3 H
8 CMe3 H
9 H H N

10 H NH3 OH

11 H Br
12 H CH2=CH2 9
SET-B R1 R2 R3

13 H H NO2
14 H I H R1 N

15 NH2 H H
16 H H H R2

HN
17 H C(CH3)3 H OH

18 H CH3 H
N
19 H NO2 H
20 H CHO H OH

21 COOH H H R3

22 CH3 H H
23 Br H H
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24 CH2CH2 H H
3.2 DOCKING AND SCORE OF SET- A and SET- B
S.N Docking Binding Lattice energy Match Lipophilic Ambig Clash Rot #match
OF (A) score affinity(∆G)KJ/ ity
mole
1 -22.2927 -29 0.29 -14.5098 -16.5249 -8.7514 6.4935 5.6000 13

2 -19.1891 -13 0.10 -17.3432 -17.5916 -8.2578 11.6034 7.0000 19

3 -18.1993 -20 0.18 -10.8574 -14.8836 -6.7626 4.7043 4.2000 14

4 -21.0692 -12 0.10 -19.1557 -16.1035 -6.0570 9.7625 4.2000 21

5 -19.8629 -27 0.24 -14.6672 -16.1035 -6.0570 7.3649 4.2000 18

6 -24.0818 -29 0-25 -14.5604 -18.9358 -8.0091 7.9057 4.2000 16

7 -24.5348 -21 0,20 -17.0573 -15.8626 -9.3723 8.1574 4.2000 17

8 -23.5676 -25 0.20 -16.7613 -15.7247 -7.4938 5.4123 5.6000 17

9 -21.8893 -43 0.41 -17.587 -16.6087 -8.5419 11.2425 4.2000 20

10 -24.3480 -46 0,43 -17.0259 -19.0379 -8.8719 10.987 4,2000 18

11 -20.8757 -29 0.31 -12.8366 -19.3519 -9.0373 10.7501 4.2000 20

12 -20.2317 -27 0.24 -11.4378 -21.5799 -9.1670 12.34 4.200 14 11

13 -27.6979 -37 0.27 -18.3517 -18.8941 -10.1515 8.3491 9.8000

14 -25.0314 -33 0.27 -20.6898 -19.9828 -10.5676 11.0087 9.8000

15 -26.8000 -45 0.36 -20.8035 -19.6899 -9.7035 8.2863 9.8000

16 -38.9456 -48 0.38 -38.0098 -20.6888 -11.9248 10.1150 9.8000

17 -22.3683 -38 0.28 -17.7756 -19.2386 -8.8618 6.9077 11.2000

18 -23.2662 -29 0.23 -18.0174 -18.2589 -9.2558 7.0659 9.8000

19 -27.4389 -33 0.24 -24.3233 -19.8706 -13.3385 14.8935 9.8000

-26.0324 -23 0.18 -26.0324 -21.8648 -18.8648 -189266 -10.6827

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21 -28.4919 -36 0.27 -22.7794 -20.8268 -13.8358 13.7501 9.8000

22 -33.4118 -37 0.30 -26.8922 -21.9492 -11.7093 11.9389 9.8000

23 -32.5432 -45 0.32 -26.5485 -21.5278 -11.5733 11.9064 9.8000

24 -33.6028 -59 0.47 -27.0132 -22.0370 -11.7027 11.9501 9.8000

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ADME OF ABOVE MOLECULES SET (A ) AND SET (B)
S.N. OF A NUMBER H- BOND H -BOND MOLAR LIPOPHILI WATER BBB[blood Pgp Drug MOLECUL
OF ACCEPTOR DONOR REFRACTI CITY SOLUBILIT brain substrate likeness[li AR
ROTATABL VITY [ilogP] Y[logS]/ barrier] pinski rule WEIGHT
E BOND fellow]

1 4 s4 3 0.913281/ 347.41
104.37 2.60 -4.87 no yes yes

2 6 4 2 -4.93 0.644/228 yes Yes/ 0 387.47

117.13 3.19 yes violated

3 4 3 2
115.07 3.39 4.57558 no No; 2 457.31
-6.19 /yes violations:
  MW>350,
XLOGP3>3.
5

4 2.69 -5.07
5 5 2 376.41 0.644228/ no No; 2 376.41
no violations:
MW>350,
XLOGP3>3.
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5 5 4 2 107.74 yes 359.42

2.90 -4.75 0.701284/ Yes; 0 g/mol 21
yes violation
6 5 5 2 107.37 2.68 -4.86 0.096363 no No; 2
8/no violations: 374.41
MW>350,
7 4 3 107.31 4.27 -5.31 4.20446/
2 yes yes No; 1 345.44
violation:
XLOGP3>3.
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8 5 3 2 8.21574/ yes No; 2
121.62 5.13 -6.28 yes violations: 387.52
MW>350,
XLOGP3>3.
5

9 3 2 102.35 3.04 -5.00 2.70794 yes No; 1

4 /yes violation: 331.41
XLOGP3>3.
5

10 4 3 3 106.75 2,68 -4.66 0.276777/ yes No; 1 346.43

no violation:
XLOGP3>3.
5
no

11 4 3 2 110.05 3.37 -5.92 8.74853/ 410.31

yes no No; 2
violations
12 5 3 2 4.46 3.08 4.51922/ 357.45
112.44 -5.56 yes no No; 2
violations: 22
 -1.21 violations:  
MW>350,
Rotors>7,
XLOGP3>3
.5
14 7 5 3 129.30 2.78 -6.37 No/ no No; 2 516.37
-1.138 violations:
MW>350,
XLOGP3>3.
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15 7 7 4 5.0617 -4.929 -1.086 no 405.5023
129.30 no No; 2
  violations:
MW>350,
XLOGP3>3.
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16 7 6 3 116.59 2.96 -5.19 No/-1.087 no No 390.48 
3 alerts:
imine_1,
oxime_1,
oxygen
17 7 6 3 135.86 3.89 -6.48 no/-1.067 yes No; 3 516.383
violations:
MW>350,
Rotors>7,
18 6 5 3 119.03 3.24 -4.186 Yes/ yes No; 2 385.467
-0.817 violations:
  MW>350,
XLOGP3>3. 23
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21 7 8 3 121.47 Yes/ yes No; 1 423.473
2.34 -4.17 -0.876 violation: 
   

20 8 6 3 -4.808 No/ yes No; 3

121.97 2.13 -1.183 violations: 418.49
    MW>350
No; 3
violations:

21 8 7 3 121.60 2.40 -5.05 No/-1.34 no No; 3 433.48

violations:

22 7 6 3 121.55 3.19 -5.49 -1.064/ no yes No; 2 404.514

violations:  
 

23 7 6 3 124.29 3.30 No/-1.151 no 469.383

-6.10 No; 2
  violations:
 

24 7 6 3 121.55 3.19 -5.49 No/-1.064 yes No; 2 404.514

violations
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sult
he binding energy (kJ/mol) divided into three parts: higher, moderate, and lower for TABLE – 12 SET A and SE

HIGHER RANGE MODERATE RANGE LOWER RANGE

     

SET –A -46 TO- 43 -29 TO -21 -20 TO -12

Ligand number 9, 10 1,5,6,7,8,12,11 2,3,4
SET – B -59 TO -45 -37 TO -33 -29 TO -23
Ligand number 15,16,23,24 13,14,17,19,21,22 18,20

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4.2The docking sore range divided into three part : higher , moderate and
lower for SET A and SET B
  HIGHER RANGE MODERATE RANGE LOWER RANGE
     

SET –A -24.5348 TO-22.2927 -21.8893 TO -20.2317 -19.8629 TO -18.1993

ligand number 1,6,7,8,10 4,9,11,12 2,3,5,

SET – B -38.9456 TO -33.6028 -32.5432 TO-26.8000 -25.0314 TO-22.3683

ligand number 15,22,24 13,16,23,19,20,21 14,17,18,

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 Set-a pharmacophore

R1 N 1,2,3,4-tetrahydroacridine

R2

HN

N-methylethanamine

toluene
N

OH

formaldehyde oxime

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SET-b
pharmacophore
R1 N
tetrahydroacridine

R2

HN OH formaldehyde oxime
N

pyridin-3-ol
OH

R3

N-methylpentan-1-amine

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Tetrahydroacridine
  The structure of tetrahydroacridine consists of a heterocyclic ring system containing four carbon atoms
and one nitrogen atom. The nitrogen atom is in a basic state and can form hydrogen bonds with other
molecules.
 The pharmacophore of tetrahydroacridine is characterized by the presence of the nitrogen atom, which
allows for interactions with the acetylcholinesterase enzyme in the brain.
 The pharmacophore also includes the carbon atoms in the heterocyclic ring system, which provide a
framework for the molecule and allow for additional modifications to be made to improve its
pharmacological properties.

Oxime Pharmacophore
 It can be considered as a derivative of formaldehyde with an oxime functional group (-NOH)
attached to the carbon atom. The pharmacophore of formaldehyde oxime is the functional
group that is responsible for its biological activity or pharmacological properties.
 The oxime functional group in formaldehyde oxime is an important pharmacophore as it has a
nitrogen atom that can act as a hydrogen bond acceptor, and the oxygen atom can act as a
hydrogen bond donor. This property of the oxime functional group allows formaldehyde oxime
to interact with biological molecules, such as proteins and enzymes, through hydrogen bonding
interactions.
 The polar functional group, which makes formaldehyde oxime soluble in polar solvents and
allows it to interact with other polar molecules.
.
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Reaming pharmacophore:
Pyridin-3-ol

 Pyridin-3-ol is a heterocyclic organic compound that contains both a pyridine ring and a hydroxyl
group (-OH) attached to the third carbon atom. The pharmacophore of pyridin-3-ol is determined
by its structural features that contribute to its biological activity.
 The electron-rich aromatic ring system of pyridin-3-ol can participate in various types of
interactions with a target, including pi-pi stacking and hydrophobic interactions.
 The molecule's flexibility can also be an advantage, as it can adopt different conformations to
optimize its interactions with a target.
N-methylpentan-1-amine pharmacophore
 N-methylpentan-1-amine is a primary amine with the chemical formula C6H15N. The molecule
contains an amine functional group (-NH2) attached to a pentane chain, with a methyl group (-
CH3) attached to the nitrogen atom.
 As a pharmacophore, the amine functional group is important as it can act as a hydrogen bond
donor and participate in electrostatic interactions with target molecules. The presence of the
pentane chain provides hydrophobic properties, which can facilitate binding to hydrophobic
regions of the target molecule.
 The methyl group on the nitrogen atom can also influence the pharmacological properties
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of N-
methylpentan-1-amine. It can affect the basicity of the amine group and can contribute to steric
hindrance, influencing the way the molecule interacts with its target.
ADMET

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