Determination of the differential effects of hydrogen bonding and water release on the binding of FK506 to native and Tyr82-->Phe82 FKBP-12 proteins using free energy simulations.

Abstract excerpt

We use the thermodynamic integration technique to calculate the free energy associated with the Tyr82-->Phe82 mutation (Y82F) in the protein FKBP-12, both free and bound to known inhibitor FK506 (tacrolimis). We find that the net difference in free energy for the two changes is 0.85 kcal/mol, with the binding of FK506 relatively more favorable for the native protein than the mutant. This net energy compares very...

Topics

• Animals
• Carrier Proteins
• Cattle
• DNA-Binding Proteins
• Heat-Shock Proteins
• Humans
• Hydrogen Bonding
• Mathematics
• Models, Molecular
• Mutation
• Phenylalanine