Molecular Modeling in Drug Repurposing

Drug repurposing or drug repositioning is a widely used strategy in drug development that seeks to identify new therapeutic indications for active pharmaceutical ingredients that are already on the market. Due to the high failure rates, costs and slowness of the discovery and development process of new drugs, repurposing drugs to treat diseases different from those that were originally defined is an increasingly important strategy. Currently, there are several research initiatives to boost drug repurposing, including REPO4EU, REMEDi4ALL and RePo-SUDOE.

Molecular Modeling techniques, namely, Molecular Docking and Molecular Dynamics (MD) simulations, often complemented with Machine Learning (ML) and Artificial Intelligence (AI) algorithms, have continuously contributed to the understanding of processes in biological systems. Examples include the characterization of the direct interaction between drugs and proteins and between drugs and cell membrane models. The application of Molecular Modeling techniques is of high value for the drug repurposing process, namely by describing how drugs can reach and interact with relevant disease targets.

Computational strategies are at the core of drug development projects. Their role spans diverse research stages, from the target identification to the drug design, prediction of drugs activity and characterization of their action mechanisms. For instance, the COVID pandemic has clearly called the attention of researchers and the public in general for the role of computational studies in drug development.

This Research Topic focuses on the mechanistic characterization and understanding of drug-target interactions via Molecular Docking and MD simulations. Docking is used to predict binding poses and interactions, while MD simulations provide a dynamic view of molecular behavior, helping to explain drug efficacy and interactions on a molecular scale. Innovative computational techniques, including the use of ML and AI, are part of this research scope to enhance the predictive accuracy and efficiency of repurposing efforts.
We invite investigators to contribute with original research articles and review articles on all aspects of molecular modeling simulations, including Docking and MD simulations, eventually complemented with ML and AI algorithms, focused on drug repurposing.

Potential topics include but are not limited to the following:
• Atomistic, coarse-grained, and multiscale MD simulations applied to drug repurposing;
• Interaction and permeation of drugs through protein-free and protein containing lipid membranes;
• Interaction of drugs with proteins identified as disease targets;
• Enhanced sampling studies in drug repurposing;
• Software, force fields, and diverse tools dedicated to drug repurposing.

Keywords: drug repurposing, Disease targets, Protein-Ligand interaction, Membrane-Drug interaction, Membrane Permeability, Molecular dynamics simulations, Molecular Docking Simulations, Enhanced sampling techniques, Machine Learning Methods, Artificial Intelligence

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.