Journey to Find the

Inhibitor of
β-Lactamase Using
Virtual Screening
EMMI 2023
TEAM MICROBE
 An Overview of β-Lactamase

β-Lactamase helps bacteria

gain antibiotic resistance
~170,000 deaths because
of MDR-TB
Virtual screening is
inexpensive and less
time consuming
Bush, Karen, and Patricia A Bradford. “Β-Lactams and β-Lactamase
Inhibitors: An Overview.” Cold Spring Harbor Perspectives in Medicine, 1 Penicillin
Aug. 2016,
 Hypothesis
We hypothesize that ceftriaxone would bind more effectively to the
β-lactamase protein than clavulanic acid would because centriaxone
has more potential for electrostatic and hydrogen bonding
interactions with the residues within the binding cavity.

Additionally we expect both will be more effective than avibactam

which does not have a beta lactam ring that would help it bind better
to the beta lactamase.

Avibactam
 Methods 1

● β-Lactamase was downloaded from RCSB (7K8F)

● Protein was cleaned and B-chain was prepared
● Redocked Ceftriaxone using GNINA in Colab

center_x center_y center_z

15 4 30

size_x size_y size_z

25 25 25
 Methods 2

● Chose 3 ligands (Ceftriaxone, Clavulanic acid, and Avibactam) due to

their high compatibility with the proteins ligand
● Searched RCSB for protein complexes that contains Clavulanic acid and
Avibactam
● Ligands were extracted using Pymol and docked to Beta lactamase

Avibactam
 Ceftriaxone RMSD RESULTS
Pose RMSD

1 3.25147

2 8.75583

3 4.5386

4 8.62712

5 9.24203

6 2.34668

7 7.09143

8 7.92447

9 3.8844
 Ceftriaxone Docking Results
mode Affinity CNN CNN
(kcal/mol) Pose score affinity

1 -7.87 0.5094 6.024

2 -7.04 0.4275 5.730

3 -9.001 0.2981 5.819

4 -8.13 0.2971 5.844

5 -7.85 0.2664 5.563

6 -7.77 0.2627 5.780

45K
7 -7.78 0.2509 6.067

8 -7.25 0.2100 5.288

9 -8.52 0.2033 5.573

 Clavulanic acid docking results
mode Affinity CNN CNN
(kcal/mol) Pose score affinity

1 -5.39 0.6821 3.822

2 -5.21 0.6765 3.599

3 -4.99 0.6659 3.724

4 -4.37 0.6429 3.652

5 -5.27 0.5599 3.899

6 -4.45 0.5036 3.405

7 -4.93 0.4855 3.535

8 -4.87 0.4780 3.588

Bank, RCSB Protein Data. “2JAP: Clavulanic Acid Dehydrogenase: 9 -5.04 0.4701 3.763
Structural and Biochemical Analysis of the Final Step in the
Biosynthesis of the Beta-Lactamase Inhibitor Clavulanic Acid.”
Avibactam docking results
mode Affinity CNN CNN
(kcal/mol) Pose score affinity

1 -6.80 0.5323 4.794

2 -5.72 0.4492 4.606

3 -4.73 0.4184 3.783

4 -5.89 0.4168 4.573

5 -6.15 0.3734 4.613

6 -5.22 0.3586 3.906

7 -4.73 0.3408 4.016

8 -6.81 0.3401 4.525

9 -5.62 0.3391 4.235

Visual comparison
 Conclusions

● Ceftriaxone is the most effective inhibitor

● Clavulanic acid is the least effective inhibitor
● Beta lactam rings are not necessary for
ligands to be successful inhibitors
● What’s Next: interactions that are important
to drive the effectiveness of ceftriaxone
● Test out different ligands such as quercetin
 THANK YOU!
Presented by:

Team Microbe 1

Saltanat Pazylbekov - PyMol Lead & Slides Designer

Rania Mahmoud - PyMol Lead
Habiba Effat - Researcher
Anasimeci Nakabea - Slides Designer
Pranavi Sammidi - Team Lead & GNINA Docking Lead