Kuşkonmaz Bileşiklerinin NDM-1 β-Laktamaza Karşı Yüksek Bağlanma Afiniteleri

Abstract

Günümüze kadar 68 varyantı tanımlanmış olan NDM-1 β-laktamaz, klinik ortamda ciddi sorunlara yol açmaktadır. Bu β-laktamaz, Dünya Sağlık Örgütü tarafından acil müdahale gerektiren patojenler listesinde yer alan mikroorganizmalarda bulunmaktadır ve bu sebeple antimikrobiyal dirençle mücadelede kritik bir hedef olarak kabul edilmektedir. Bu çalışmada, NDM-1 β-laktamaz hedef olarak seçilmiş ve Asparagus officinalis (kuşkonmaz) bitkisinde mevcut olan bileşiklerin bu hedefe yönelik tahmini bağlanma enerjilerinin hesaplanmasına odaklanılmıştır.Bu doğrultuda, söz konusu bitkide bulunan 2460 bileşik, Plant Metabolic Network (PMN) veri tabanı üzerinden temin edilmiştir. Hazırlanan ligandlar, Autodock Vina yazılımı aracılığıyla moleküler kenetleme (molecular docking) yöntemi kullanılarak NDM-1’in aktif bölgesine yerleştirilmiştir. Sanal tarama sonuçları doğrultusunda, en yüksek potansiyele sahip ilk 20 bileşiği içeren bir liste oluşturulmuştur. Mevcut NDM-1 inhibitör adayı olan magnololün bağlanma skorları ile kıyaslandığında, hazırlanan listedeki ilk 20 bileşiğin bağlanma skorlarını oldukça düşük olduğu saptanmıştır. Özellikle delfinidin, antosiyanin, izoeritin türevleri ve neoksantinin, NDM-1 β-laktamazın aktif bölgesine düşük bağlanma skoru sergilediği gözlemlenmiştir. Gelecekte, bu bileşiklerin NDM-1 β-laktamazına karşı yeni inhibitör adayları olarak potansiyellerini daha kapsamlı bir şekilde incelemek amacıyla in vitro analizler gerçekleştirilebilir.

Keywords

• NDM-1 β-laktamaz
• Autodock Vina
• Asparagus officinalis
• antimikrobiyal direnç
• sanal tarama.

High Binding Affinities of Asparagus Compounds to NDM-1 β Lactamase

Abstract

NDM-1 β lactamase, of which 68 variants have been identified to date, causes serious problems in the clinic. This β-lactamase is found in pathogens that require urgent action from the World Health Organization and is therefore an important target in the fight against antimicrobial resistance. In this study, NDM-1 β-lactamase was selected as the target and we focused on calculation of the estimated binding energies of the compounds found in the Asparagus officinalis to this target. For this purpose, 2460 compounds found in this plant were downloaded from the Plant Metabolic Network (PMN) database. The prepared ligands were docked to the active site of NDM-1 by molecular docking using Autodock Vina. According to the virtual screening results, a list of the top 20 compounds was prepared. When compared to the NDM-1 docking score of the NDM-1 inhibitor candidate magnolol, it was seen that the binding score of the compounds in the top 20 list were high. It was observed that delphinidin, anthocyanin, isoerythin derivatives and neoxanthin had low docking score to the active site of NDM-1 β-lactamase. In vitro analyzes can be performed to investigate the potential of these compounds as inhibitor candidates against NDM-1 β-lactamase in the future.

Keywords

• NDM-1 β-lactamase
• Autodock Vina
• Asparagus officinalis
• antimicrobial resistance
• virtual screening

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