Pymol, a program for visualizing 3D moleculalr sturuction, as well as bonding interaction with the receptor, is used.  Here, I will be conducing analysis over "which is the better antagonist?" by comparing two given antagonsit, A and B.

Antagonists

Antagonists are drugs that blocks off receptors to prevent the natural ligands from binding. This could be non-covalent interactions between each molecule but is not limited to.  The model antagonist must fit/have similar size and shape comparing to the original natural ligands, since it must match the position and orientation. Here, successful antagonist does binds to the receptor with high affinity, however, it does not activates the receptor, by blocking the endogenous ligands. In real life example, caffeine blocks adenosine from AZA receptor. 

Various medical disorders including hypertension, asthma, and chronic pain are all capable of being treated using antagonists. For instance, beta-blockers, which act as adrenaline antagonists and prevent its effects, are prescribed to treat hypertension and heart failure. Allergies are treated using antihistamines, which are histamine antagonists that suppress histamine's effects.

It's crucial to understand that antagonists are occasionally chemicals that bind to a receptor but have no impact. These compounds are not regarded as antagonists because they may bind to the receptor but have no impact because they do not activate the signalling pathways downstream of the receptor.

Interactions

In both antagonists, the H-bonds are not the only interaction present. These are, hydrophobic, and pi-cation interactions(ion-dipole). Additionally, by analyzing the structure alone, it is able to assume there  could be possible induced dipole moments.

Ion dipole

Ion-dipole is an intermolecular bonding force between charged group and dipole of the other molecule. Here, it tends to be stronger than dipole-dipole bond, where dipole-dipole is only between slightly positive and slightly negative charge whereas ion-dipole is on charged group interacting with dipole.

The magnitude of the charges and the separation between them determine how strong an ion-dipole interaction is. The strength of the interaction increases with both the ion's charge and the polar molecule's dipole moment. Additionally, as the separation between the ion and polar molecule widens, the intensity of the connection weakens.

Hydrophobic interaction

The tendency of non-polar molecules or groups to assemble in aqueous solutions due to their resistance to water molecules is referred to as hydrophobic interaction. This occurs because water molecules form a tightly structured network of hydrogen bonds with one another, and the presence of hydrophobic compounds disrupts this network.

The hydrophobic effect is a thermodynamic phenomenon caused by the system's entropy. When hydrophobic molecules cluster, the amount of water molecules arranged around non-polar groups decreases, causing the entropy of the water molecules to increase. The hydrophobic effect is driven by this increase in entropy.

Hydrophobic interactions play an important role in biological systems for protein folding and stabilization, as well as the creation of lipid bilayers and the binding of hydrophobic ligands to proteins. The hydrophobic effect also plays a role in the production of micelles and other self-assembled structures in solution, as hydrophobic molecules gather together to reduce their exposure to water molecules.

Induced dipole moments 

With the characteristics of aromatic ring, where the center of the ring tends to be slightly charged (negatively charged), here the charged functional group (ex. R-NR3+) will have interaction.

These intermolecular bonding force will be used as guidance for drug to successfully bind to their desired binding site. 

3D structure

With Pymol, I have visualized H-bond present between the protein complex and the antagonist within distance of 3.0A.  However, by looking at 2D structure above, we already know that H-bond isn't the only interaction. Below is a list of interaction matching which interaction with which protein. For instance, T117 Hydrophobic interaction with Benzene. This means Theornine which is in 117th position will have hydrophobic interaction with Benzene of the antagonist. 

Antagonist A

N333 H-Bond with tertiary amine 2.9Å 

N333 H-Bond with secondary amine 2.9Å 

R336 H-Bond with oxygen on carboxyl group 2.6Å 

F330 Hydrophobic interaction to carbon (Methyl Benzene group)

L347 Hydrophobic interaction to carbon (Indole functional group)

I352 Hydrophobic interaction with carbon (Indole functional group)

R336 Pi-Cation interaction with aromatic ring (Indole functional group

R336 Pi-Cation interaction with aromatic ring (indole functional group)

R336 Ionic interaction with carboxylate

Antagonist B

T117 Hydrophobic interaction with aromatic ring (Benzene)

T118 Hydrophobic interaction with aromatic ring (Methyl Benzene)

Y176 Hydrophobic interaction with aromatic ring (Methyl Benzene) 

F330 Hydrophobic interaction with aromatic ring (Methyl Benzene)

A332 Hydrophobic interaction with aromatic ring (indole group)

A343 Hydrophobic interaction with aromatic ring (indole group)

L347 Hydrophobic interaction with aromatic ring(indole group) 

I352 Hydrophobic interaction with aromatic ring(indole group) 

N333  H-bond with pyrimidine 2.8Å  apart 

A336 H-bond with oxygen of the secondary amide and is 3.1Å apart

R336 pi-cation interaction with oxygen(hydrogen bond)  and aromatic ring(center of indole).

Through analysis

Two antagonists seemed very similar when briefly looked. However, the carboxylic group on the antagonist A which as hydrogen accepting characteristics(but weak since of resonance) are unique compared to the Antagonist B. The Antagonist B has extra aromatic ring, which would have VDW interaction(hydrophobic) with other residues. 

Both antagonist A and B have amide group which are poor HBA since of resonance structures(amides at the center of the molecule). However, antagonist A will have worse interaction since there's another resonance structure in the carboxylic group attached to indole(meanwhile, Antagonist B has full indole structure benefiting HBA-HBD from it). Additionally, one of the aromatic ring of Antagonist has single Cl on it, decreasing VDW of the overall structure. Antagonist B has more aromatic rings anyways, This could be used for not only VDW force but also in induced dipole or pi interactions with other residues. Overall, when labeled each antagonist’s charge and HBA/HBD, we can see there's significant amount of HBA which would interact with residues with HBD, and vice versa, HBD which will interact with HBA. The presence of ionic charges will be ignored here since all charges is a product of resonance, lowering the H-bond intensity. Therefore, the antagonist B will be expected to have stronger binding interaction(when used as drug, will increase the EC50 value).

Bonding interactions

The image above is created by PLIP, to show interaction of our model antagonist with other residues of the protein compliment. Here, we can clearly see Antagonist B has made better interaction with the surrounding residues. Note that the extra H-bond on Antagonist A is within the indole, where its part of a induced dipole.