Mixed Solvent Molecular Dynamics (MxMD)
Mixed Solvent Molecular Dynamics (MxMD) can be used to identify and characterize active sites and interfaces along a solute’s surface. The solute can be a protein or DNA or RNA. MxMD performs molecular dynamics simulations in binary solvent mixtures, consisting of water and small organic probes — the cosolvents — that mimic binding counterparts to the solute.
MxMD takes full flexibility of the solute into account as well as competition of cosolvent probes with water, thus making it a powerful approach for hotspot mapping and assessing “druggability” of competitive and allosteric binding sites [4]. The predefined cosolvent probes are carefully selected to enable the identification and characterization of hydrogen-bonding sites, hydrophobic contacts, protein-protein interfaces, and aromatic pockets. MxMD can be further adapted to identify other functionally relevant sites by tailoring the cosolvent probe combination.
The MxMD workflow follows the procedure detailed in Ref. 2.
MxMD Simulations