MxMD Cosolvent Probes

The MxMD workflow supports both miscible and immiscible cosolvent probes. The miscible probes are water-miscible and mix evenly in MxMD simulations without phase separation [3]. The immiscible probes do not mix with water and are useful for sampling hydrophobic and aromatic interactions. Their potentials are modified so that they do not aggregate in water. These probes are particularly effective for locating cryptic pockets, as they can stabilize transiently exposed binding sites and increase their residence time during the simulation. Both sets of probes are optimized for detecting protein hotspots. For DNA/RNA targets, you might want to use MxMD Custom Cosolvent Probes.

Each probe includes ten distinct pre-equilibrated solvent boxes that are used to assemble the initial cosolvent systems.

Table 1. Cosolvent probes for MxMD. Default probes are acetonitrile, isopropanol, and pyrimidine (their names are highlighted in bold).

Name	Type	PDB Residue Type	2D Structure	Chemical Formula	Mapping Role
1,3-Oxazinan-2-one	Immiscible	OX2		C₄H₇NO₂	6-membered aliphatic; H-bond donor/acceptor
1-Methyl-1H-Indazole	Immiscible	MI1		C₈H₈N₂	Aromatic; H-bond acceptor
1-Naphthol	Immiscible	1NP		C₁₀H₈O	Aromatic; H-bond donor
1H-Indazole	Immiscible	LZ1		C₇H₆N₂	Aromatic; H-bond donor/acceptor
2-Cyanophenol	Immiscible	0R0		C₇H₅NO	6-membered aromatic; H-bond donor/acceptor
2-Methyl-2H-Indazole	Immiscible	MI2		C₈H₈N₂	Aromatic; H-bond acceptor
2-Naphthol	Immiscible	2NP		C₁₀H₈O	Aromatic; H-bond donor
2H-Indazole	Immiscible	LZ2		C₇H₆N₂	Aromatic; H-bond donor/acceptor
3-Cyanophenol	Immiscible	0R3		C₇H₅NO	6-membered aromatic; H-bond donor/acceptor
4-Cyanophenol	Immiscible	0R4		C₇H₅NO	6-membered aromatic; H-bond donor/acceptor
Acetaldehyde	Miscible	ACD		C₂H₄O	Polar; H-bond acceptor
Acetamide	Miscible	ACM		C₂H₅NO	Polar; H-bond acceptor/donor
Acetic Acid	Miscible	ACY		C₂H₄O₂	Polar; H-bond acceptor/donor
Acetone	Miscible	ACN		C₃H₆O	Polar; H-bond acceptor
Acetonitrile	Miscible	CCN		C₂H₃N	Polar; amphipathic
Androstenol	Immiscible	AND		C₁₉H₃₀O	Hydrophobic; H-bond donor
Benzene	Immiscible	BNZ		C₆H₆	6-membered aromatic; hydrophobic
Benzothiazole	Immiscible	BZL		C₇H₅NS	Aromatic; H-bond acceptor
Cyanobenzene	Immiscible	B1X		C₇H₅N	6-membered aromatic; H-bond acceptor
Diethylamine	Miscible	DME		C₄H₁₁N	H-bond donor; amphipathic
Dimethylsulfoxide / DMSO	Miscible	DMS		C₂H₆OS	Polar; H-bond acceptor
Ethanol	Miscible	EOH		C₂H₆O	Polar; H-bond donor
Formamide	Miscible	ARF		CH₃NO	Polar; H-bond acceptor/donor
Furan	Immiscible	FUR		C₄H₄O	5-membered aromatic; H-bond acceptor
Glycerol	Miscible	GOL		C₃H₈O₃	Polar; H-bond donor
Imidazole	Miscible	IMD		C₃H₄N₂	5-membered polar aromatic
Isatin	Immiscible	ISN		C₈H₅NO₂	Aromatic; H-bond donor/acceptor
Isobutane	Immiscible	ISB		C₄H₁₀	Small aliphatic; hydrophobic
Isonicotinonitrile	Immiscible	4NN		C₆H₄N₂	6-membered aromatic; H-bond acceptor
Isopropanol	Miscible	IPA		C₃H₈O	H-bond donor/acceptor; small hydrophobic
Isopropylamine	Miscible	ISP		C₃H₉N	H-bond donor; small hydrophobic
Isoquinoline	Immiscible	ISQ		C₉H₇N	Aromatic; H-bond acceptor
Isoquinolinone 1	Immiscible	IQ1		C₉H₇NO	Aromatic; H-bond donor/acceptor
Isoquinolinone 2	Immiscible	IQ2		C₉H₇NO	Aromatic; H-bond donor/acceptor
Methylamine	Miscible	NME		C₁H₅N	Small hydrophobic
Methylsulfonylmethane/DMSO2	Miscible	7SU		C₂H₆O₂S	Polar; H-bond acceptor
Morpholine	Miscible	6LR		C₄H₉NO	6-membrane; polar
N-Methylacetamide	Miscible	NML		C₃H₇ON	Protein backbone-like
Nicotinonitrile	Immiscible	3NN		C₆H₄N₂	6-membered aromatic; H-bond acceptor
Oxane	Immiscible	OXA		C₅H₁₀O	6-membered aliphatic; H-bond acceptor
Oxazole	Miscible	OXZL		C₃H₃NO	5-membered aromatic; polar
Oxirane	Immiscible	OXO		C₂H₄O	3-membered aliphatic; H-bond acceptor
Oxiranemethanol	Miscible	OX9		C₃H₆O₂	3-membered aliphatic; H-bond donor/acceptor
Phenol	Immiscible	IHP		C₆H₆O	6-membered aromatic; H-bond donor
Picolinonitrile	Immiscible	2NN		C₆H₄N₂	6-membered aromatic; H-bond acceptor
Piperidine	Miscible	PIP		C₅H₁₁N₁	6-membered aliphatic; H-bond donor
Propyne	Immiscible	PYN		C₃H₄	Small aliphatic; hydrophobic
Pyrazine	Miscible	1P4		C₄H₄N₂	6-membered aromatic
Pyridazine	Miscible	1P2		C₄H₄N₂	6-membered aromatic
Pyridine	Miscible	PYR		C₅H₅N₁	6-membered aromatic
Pyrimidine	Miscible	P1R		C₄H₄N₂	6-membered aromatic
Quinoline	Immiscible	QNL		C₉H₇N	Aromatic; H-bond acceptor
Resorcinol	Miscible	RCO		C₆H₆O₂	H-bond donor/acceptor; 6-membered aromatic
Sulfamide	Miscible	FUS		H₄N₂O₂S	Polar; H-bond donor/acceptor
Thiazole	Miscible	THZL		C₃H₃NS	5-membered aromatic
Triethylamine	Miscible	TME		C₆H₁₅N	Small hydrophobic
Trifluoroethanol	Miscible	TFE		C₂H₃F₃O	Polar; H-bond donor/acceptor
Urea	Miscible	URE		CH₄N₂O	Polar; H-bond donor/acceptor