The nature of trypsin-pancreatic trypsin inhibitor binding: free energy calculation of Tyr39-->Phe39 mutation in trypsin.
The main goal of this work is the detailed study of the binding interactions in the trypsin-pancreatic trypsin inhibitor (PTI) complex and, here, we present how meaningful the Tyr39-Ile19 interaction is to the stability of that particular complex using free energy methods. This knowledge should be very important in the design of new inhibitors for trypsin and enzymes homologous to it. In particular, it could help to decide whether it is possible to produce selective inhibitors for these enzymes by appropriate mutations of residues in the contact region of PTI.
Melo
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CEQUP/Departamento de Química, Faculdade de Ciências, Universidade do Porto, Portugal.
Ramos
M J
MJ
D019943:Amino Acid Substitution; D004795:Enzyme Stability; D015394:Molecular Structure; D017354:Point Mutation; D013816:Thermodynamics; D014357:Trypsin / Q000737:chemistry*; D014359:Trypsin Inhibitor, Kazal Pancreatic / Q000737:chemistry*; D014443:Tyrosine / Q000737:chemistry*
D014443:Tyrosine; D014359:Trypsin Inhibitor, Kazal Pancreatic; D014357:Trypsin