Molecular docking has been widely employed as a fast and inexpensive technique in the past decades, both in academic and industrial settings. Although this discipline has now had enough time to consolidate, many aspects remain challenging and there is still not a straightforward and accurate route to readily pinpoint true ligands among a set of molecules, nor to identify with precision the correct ligand conformation within the binding pocket of a given target molecule. Nevertheless, new approaches continue to be developed and the volume of published works grows at a rapid pace. In this review, we present an overview of the method and attempt to summarise recent developments regarding four main aspects of molecular docking approaches: (i) the available benchmarking sets, highlighting their advantages and caveats, (ii) the advances in consensus methods, (iii) recent algorithms and applications using fragment-based approaches, and (iv) the use of machine learning algorithms in molecular docking. These recent developments incrementally contribute to an increase in accuracy and are expected, given time, and together with advances in computing power and hardware capability, to eventually accomplish the full potential of this area.

A class of drugs in use for treating type II diabetes mellitus (T2D), typified by the pseudotetrasaccharide acarbose, act by inhibiting the alpha-glucosidase activity present in pancreatic secretions and in the brush border of the small intestine. Herein, we report the synthesis of a series of 4-substituted 1,2,3-triazoles conjugated with sugars, including D-xylose, D-galactose, D-allose, and D-ribose. Compounds were screened for alpha-glucosidase inhibitory activity using yeast maltase (MAL12) as a model enzyme. Methyl-2,3-O-isopropylidene-beta-D-ribofuranosides, such as the 4-(1-cyclohexenyl)-1,2,3-triazole derivative, were among the most active compounds, showing up to 25-fold higher inhibitory potency than the complex oligosaccharide acarbose. Docking studies on a MAL12 homology model disclosed a binding mode consistent with a transition-state-mimicking mechanism. Finally, the actual pharmacological potential of this triazole series was demonstrated by the reduction of postprandial blood glucose levels in normal rats. These compounds could represent new chemical scaffolds for developing novel drugs against T2D.

In this paper the aggregation of asphaltenes is studied for two asphaltene molecule families, namely PA3 and CA22 analogues, based on the work of Schuler et al. (JACS, 2015, 137, 31, 9870). The chemical characteristics of these molecules were screened by changing the heteroatoms on the backbone and the lateral chain-ends. These molecules were mixed together with different relative concentrations and for the first time the aggregation of different asphaltenes was determined using molecular dynamics simulations (MDS). The results show that the interaction energies vary for different heteroatom arrangement within a given structure and depend on the type of asphaltene. Moreover, we showed that the chain-ends have a crucial role on this phenomenon.

We present molecular dynamics simulations (MDS) for interpreting the molecular aggregation of four different asphaltene molecular models. These simulations are based on recent small-angle X-ray scattering (SAXS) and small-angle neutron scattering (SANS) experiments from Eyssautier and co-workers [