Uses of Molecular Docking Simulations in Elucidating Synergistic, Additive, and/or Multi-Target (SAM) Effects of Herbal Medicines.

The philosophy of herbal medicines is that they contain multiple active components that target many aspects of a given disease. This is in line with the recent multiple-target strategy adopted due to shortcomings with the previous "magic bullet", single-target strategy. The complexity of biological systems means it is often difficult to elucidate the mechanisms of synergistic, additive, and/or multi-target (SAM) effects. However, the use of methodologies employing molecular docking offers some insight into these. The aim of this work was to review the uses of molecular-docking simulations in the detection and/or elucidation of SAM effects with herbal medicines. Molecular docking has revealed the potential for SAM effects with many different, individual herbal medicines. Docking can also improve the fundamental understanding of SAM effects as part of systems biology approaches, such as providing quantitative weightings for the connections within static networks or supplying estimates of kinetic parameters for dynamic metabolic networks. Molecular docking can also be combined with pharmacophore modeling in a hybrid method that greatly improves the efficiency of screening. Overall, molecular docking has been shown to be a highly useful tool to provide evidence for the efficacy of herbal medicines, previously only supported by traditional usage.