Journal:JBSD:24

Insights into the drug resistance induced by the BaDHPS mutations: molecular dynamic simulations and MM/GBSA studies

Wen-Ting Chu, Ji-Long Zhang, Qing-Chuan Zheng, Lin Chen, Qiao Xue, and Hong-Xing Zhang ^[1]

Molecular Tour
Drug resistance has been an urgent problem that severely limits the therapy of current clinical microbial diseases. Sometimes, it generally correlates with mutations to the dihydropteroate synthase (DHPS) gene. In the current study, we focus on the molecular dynamic behaviors and binding free energy calculations of wild-type (wt) form and mutated form B. anthracis dihydropteroate synthase (BaDHPS) to search for the relationship between mutation and drug resistance. After 20ns MD simulations on the wt form and mutated form enzymes, it is obvious that mutation D184N and K220Q have much lower binding affinity to the inhibitor DHP-STZ than the wt form enzyme. Mutation will cause conformational change, which mainly locate on some loop region around the binding site (Loop 1, Loop 2 and Loop 7). These results may be helpful for further drug resistance and de novo drug design investigations.