Computer aided molecular modeling of anti-tuberculosis drugs

Name: Pimonluck Sittikornpaiboon

keyword: Tuberculosis

; 2,4-Diaminopyrimidine derivative

; Quantum chemistry

; Molecular dynamics simulations

; Molecular docking

; Protein-ligand interaction

; Dihydrofolate reductase

Abstract: Mycobacterium tuberculosis (mtb) is a human pathogen that causes Tuberculosis (TB). According to the rapid growth of the new multidrug-resistant TB and the fatality of the disease, the development of high efficacy drugs for TB is needed. Dihydrofolate reductase (DHFR, EC 1.5.1.3) is an essential enzyme for the folate biosynthesis pathway of eukaryotic and prokaryotic cells. An enzyme DHFR was facilitated in the conversion of substrate dihydrofolate to the product tetrahydrofolate, which is an important precursor for DNA synthesis. Therefore, the inhibition of mtbDHFR enzyme can terminate the synthesis of essential proteins and molecules for the growth of bacteria. In this study, mtbDHFR was selected as a drug target to develop the effective inhibitor for anti-mtbDHFR. This work focuses on the use of molecular modeling to investigate the interactions between the selected ligands on mtbDHFR, which target to identify the binding affinities and the mode of interaction. Quantum chemistry calculations, molecular docking and molecular dynamics simulations were used to predict the four ternary systems of mtbDHFR complex with NADPH and three difference inhibitors, which are 2,4-diaminopyrimidine derivative compounds (P1, P157, and P169) and its substrate, dihydrofolate. The results provided the key interactions in the binding site which are important for the designing of more effective compound against mtbDHFR

Thammasat University. Thammasat University Library

Address: BANGKOK

Email: preserv@tu.ac.th

Name: Luckhana Lawtrakul

Role: advisor

Created: 2016

Modified: 2021-06-29

Issued: 2021-06-29

วิทยานิพนธ์/Thesis

application/pdf

DOI: 10.14457/TU.the.2016.1685

eng

DegreeName: Doctor of Philosophy

Level: Doctoral Degree

Descipline: Engineering and Technology

Grantor: Thammasat University

©copyrights Thammasat University

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