Applications of Molecular Simulation in the Discovery of Antituberculosis Drugs: A Review

Abstract

: After decades of efforts, tuberculosis has been well controlled in most places. The existing drugs are no longer sufficient for the treatment of drug-resistant Mycobacterium tuberculosis due to significant toxicity and selective pressure, especially for XDR-TB. In order to accelerate the development of high-efficiency, low-toxic antituberculosis drugs, it is particularly important to use Computer Aided Drug Design (CADD) for rational drug design. Here, we systematically reviewed the specific role of molecular simulation in the discovery of new antituberculosis drugs. : The purpose of this review is to overview current applications of molecular simulation methods in the discovery of antituberculosis drugs. Furthermore, the unique advantages of molecular simulation was discussed in revealing the mechanism of drug resistance. : The comprehensive use of different molecular simulation methods will help reveal the mechanism of drug resistance and improve the efficiency of rational drug design. : With the help of molecular simulation methods such as QM/MM method, the mechanisms of biochemical reactions catalyzed by enzymes at atomic level in Mycobacterium tuberculosis has been deeply analyzed. QSAR and virtual screening both accelerate the development of highefficiency, low-toxic potential antituberculosis drugs. Improving the accuracy of existing algorithms and developing more efficient new methods for CADD will always be a hot topic in the future. It is of great value to utilize molecular dynamics simulation to investigate complex systems that cannot be studied in experiments, especially for drug resistance of Mycobacterium tuberculosis.

Study on the allosteric activation mechanism of SHP2 via elastic network models and neural relational inference molecular dynamics simulation

“…Molecular dynamics (MD) simulation, based on Newtonian mechanics, is one of the important techniques used to study the thermodynamic and kinetic properties of biomolecules. 43,44 In this work, three independent MD simulations at 300 K were performed for the SHP2 systems with the AMBER20 package, 45 where OL15 and ff14SB force field parameters were respectively adopted for the nucleic acid and protein atoms. 46 It should be noted that the SHP2 (SH2 structural domain only) system studied was based on the crystal structure (PDB ID: 2SHP) with all solutes dissolved in the octahedral box with the boundary of 15.0 Å using the TIP3P water model.…”

An Overview of Molecular Dynamic Simulation for Corrosion Inhibition of Ferrous Metals

“…Other than the corrosion field, MD simulation also offers numerous advantages in various sectors such as renewable energy generation, food technology, medicine, and pharmaceutical [15][16][17][18]. A broad list of reviews of MD simulation application for corrosion sector as well as other sectors had been published in the literature [14,[19][20][21][22]. In this context, numerous works have shown that MD simulation is a promising method to obtain the molecular level information of a system.…”