Journal: Journal of Chemical Information and Modeling

Article Title: Effect of Water Networks On Ligand Binding: Computational Predictions vs Experiments

doi: 10.1021/acs.jcim.4c01291

Figure Lengend Snippet: Water molecules in experimental structures of trypsin. Water molecules highlighted with orange spheres are removed from the binding site after ligand binding, while those highlighted with green spheres are retained across all structures. Water molecules highlighted with magenta spheres have no counterpart in the apo structure. (A) Joint X-ray/neutron diffraction structure of trypsin in its apo form (PDB ID 5MOP ). (B–D) X-ray structures of trypsin complexed with (B) BA (PDB ID 1S0R ), (C) 4-NH2-BA (PDB ID 3GY4 ), and (D) 4-OCH3-BA (PDB ID: 7WA2 ).

Article Snippet: 4-Amidinobenzamide hydrochloride ( 4-CONH2-BA , CAS: 59855-11-7, cat. no. OR-2209), 4-methoxybenzenecarboximidamide hydrochloride ( 4-OCH3-BA , CAS: 51721-68-7, cat. no. QB-3215), benzamidine hydrochloride ( BA , CAS: 1670-14-0, cat. no. OR-0201), 4-aminobenzamidine hydrochloride ( 4-NH2-BA , CAS: 2498-50-2, cat. no. OR-2207), thiophene-2-sulfonamide ( TP-2-SA , CAS: 6339-87-3, cat. no. OR-1553), 2-fluorobenzenesulfonamide ( 2-F-SA , CAS: 30058-40-3, cat. no. QA-4700), and sulfanilamide ( 4-NH2-SA , CAS: 63-74-1, cat. no. AN-2948) were obtained from Combi-Blocks; 1-benzofuran-2-sulfonamide ( BF-2-SA , CAS: 124043-72-7, cat. no. EN300-279329), thiazole-2-sulfonamide ( TA-2-SA , CAS: 113411-24-8, cat. no. EN300-107045), 1,3-benzothiazole-2-sulfonamide ( BTA-2-SA , CAS: 433-17-0, cat. no. EN300-60766), 4-methylbenzenesulfonamide ( 4-CH3-SA , CAS: 70-55-3, cat. no. EN300-15721), 1 H -1,3-benzodiazole-2-sulfonamide ( BDA-2-SA , CAS: 5435-31-4, cat. no. EN300-61671), and 4-methyl-benzene-1-carboximidamide hydrochloride ( 4-CH3-BA , CAS: 6326-27-8, cat. no. EN300-73561) were obtained from Enamine; 4,5,6,7-tetrahydro-1-benzothiophene-2-sulfonamide ( THBT-2-SA , CAS: 142294-64-2, cat. no. AS-8962) was obtained from Key Organics/BIONET.

Techniques: Binding Assay, Ligand Binding Assay

Journal: Journal of Chemical Information and Modeling

Article Title: Effect of Water Networks On Ligand Binding: Computational Predictions vs Experiments

doi: 10.1021/acs.jcim.4c01291

Figure Lengend Snippet: Water molecules predicted by WaterFLAP inside the binding site of trypsin, with all waters labeled with their calculated Δ G values from WaterFLAP. H-bonds are shown as orange dashed lines. (A) Empty binding site of trypsin filled with water molecules. There is one “happy” (blue) and 12 bulk-like (gray) waters inside the binding site. Squared waters are displaced upon the binding of 4-CONH2-BA and 4-OCH3-BA , the circled water molecules are displaced by all ligands except BA , and the rest of the water molecules, including the “happy” water, are displaced by all ligands. (B) BA has one “unhappy” (yellow) and eight bulk-like water molecules in its proximity and establishes an H-bond with the “unhappy” water. (C) 4-NH2-BA has one “happy” and eight bulk-like water molecules in its proximity and establishes H-bonds with the S195 residue and three bulk-like waters. (D) 4-CONH2-BA has two “unhappy” and 10 bulk-like water molecules in its proximity and establishes H-bonds with both “unhappy” waters and five bulk-like waters. (E) 4-CH3-BA has one “happy” and seven bulk-like water molecules in its proximity and establishes an H-bond with a bulk-like water. (F) 4-OCH3-BA has two “unhappy” and 12 bulk-like water molecules in its proximity and establishes H-bonds with both “unhappy” waters and two bulk-like waters.

Article Snippet: 4-Amidinobenzamide hydrochloride ( 4-CONH2-BA , CAS: 59855-11-7, cat. no. OR-2209), 4-methoxybenzenecarboximidamide hydrochloride ( 4-OCH3-BA , CAS: 51721-68-7, cat. no. QB-3215), benzamidine hydrochloride ( BA , CAS: 1670-14-0, cat. no. OR-0201), 4-aminobenzamidine hydrochloride ( 4-NH2-BA , CAS: 2498-50-2, cat. no. OR-2207), thiophene-2-sulfonamide ( TP-2-SA , CAS: 6339-87-3, cat. no. OR-1553), 2-fluorobenzenesulfonamide ( 2-F-SA , CAS: 30058-40-3, cat. no. QA-4700), and sulfanilamide ( 4-NH2-SA , CAS: 63-74-1, cat. no. AN-2948) were obtained from Combi-Blocks; 1-benzofuran-2-sulfonamide ( BF-2-SA , CAS: 124043-72-7, cat. no. EN300-279329), thiazole-2-sulfonamide ( TA-2-SA , CAS: 113411-24-8, cat. no. EN300-107045), 1,3-benzothiazole-2-sulfonamide ( BTA-2-SA , CAS: 433-17-0, cat. no. EN300-60766), 4-methylbenzenesulfonamide ( 4-CH3-SA , CAS: 70-55-3, cat. no. EN300-15721), 1 H -1,3-benzodiazole-2-sulfonamide ( BDA-2-SA , CAS: 5435-31-4, cat. no. EN300-61671), and 4-methyl-benzene-1-carboximidamide hydrochloride ( 4-CH3-BA , CAS: 6326-27-8, cat. no. EN300-73561) were obtained from Enamine; 4,5,6,7-tetrahydro-1-benzothiophene-2-sulfonamide ( THBT-2-SA , CAS: 142294-64-2, cat. no. AS-8962) was obtained from Key Organics/BIONET.

Techniques: Binding Assay, Labeling, Residue

Journal: Journal of Chemical Information and Modeling

Article Title: Effect of Water Networks On Ligand Binding: Computational Predictions vs Experiments

doi: 10.1021/acs.jcim.4c01291

Figure Lengend Snippet: Water molecules predicted by WaterFLAP inside the binding site of CAII, labeled with their calculated Δ G values. Interactions are shown as orange dashed lines. (A) Empty binding site of CAII filled with water molecules. There are two “very unhappy” (red, Δ G ≥ 3 kcal/mol) and nine bulk-like (gray) waters inside the binding site. These water molecules are displaced upon ligand binding, with the circled water molecules only displaced by the four ligands containing fused heteroaromatic rings ( BTA-2-SA , BF-2-SA , BDA-2-SA , and THBT-2-SA ). The T199 and V121 residues are labeled. (B) Binding mode of TP-2-SA in CAII, with one “unhappy” and seven bulk-like water molecules in its proximity. (C) Binding mode of TA-2-SA in CAII, with one “unhappy” and eight bulk-like water molecules in its proximity and an H-bond with the T199 side chain. (D) Binding mode of BDA-2-SA in CAII, with one “unhappy” and eight bulk-like water molecules in its proximity and an H-bond with a bulk-like water molecule. (E) Binding mode of 2-F-SA in CAII, with two “unhappy” and six bulk-like water molecules in its proximity. (F) Binding mode of 4-NH2-SA in CAII, with one “unhappy” and nine bulk-like water molecules in its proximity and three H-bonds with two bulk-like waters and with the “unhappy” water molecule.

Article Snippet: 4-Amidinobenzamide hydrochloride ( 4-CONH2-BA , CAS: 59855-11-7, cat. no. OR-2209), 4-methoxybenzenecarboximidamide hydrochloride ( 4-OCH3-BA , CAS: 51721-68-7, cat. no. QB-3215), benzamidine hydrochloride ( BA , CAS: 1670-14-0, cat. no. OR-0201), 4-aminobenzamidine hydrochloride ( 4-NH2-BA , CAS: 2498-50-2, cat. no. OR-2207), thiophene-2-sulfonamide ( TP-2-SA , CAS: 6339-87-3, cat. no. OR-1553), 2-fluorobenzenesulfonamide ( 2-F-SA , CAS: 30058-40-3, cat. no. QA-4700), and sulfanilamide ( 4-NH2-SA , CAS: 63-74-1, cat. no. AN-2948) were obtained from Combi-Blocks; 1-benzofuran-2-sulfonamide ( BF-2-SA , CAS: 124043-72-7, cat. no. EN300-279329), thiazole-2-sulfonamide ( TA-2-SA , CAS: 113411-24-8, cat. no. EN300-107045), 1,3-benzothiazole-2-sulfonamide ( BTA-2-SA , CAS: 433-17-0, cat. no. EN300-60766), 4-methylbenzenesulfonamide ( 4-CH3-SA , CAS: 70-55-3, cat. no. EN300-15721), 1 H -1,3-benzodiazole-2-sulfonamide ( BDA-2-SA , CAS: 5435-31-4, cat. no. EN300-61671), and 4-methyl-benzene-1-carboximidamide hydrochloride ( 4-CH3-BA , CAS: 6326-27-8, cat. no. EN300-73561) were obtained from Enamine; 4,5,6,7-tetrahydro-1-benzothiophene-2-sulfonamide ( THBT-2-SA , CAS: 142294-64-2, cat. no. AS-8962) was obtained from Key Organics/BIONET.

Techniques: Binding Assay, Labeling, Ligand Binding Assay