Conformational change of a globular protein elucidated at atomic resolution. Theoretical and nuclear magnetic resonance study.
A powerful method of conformational energy minimization which uses both first and second derivatives of the energy function is applied both to a small globular protein, bovine pancreatic trypsin inhibitor (BPTI), consisting of 58 amino acid residues and to its chemical derivative obtained by carboxamidomethylation of cysteinyl residues of the 14-38 disulphide bond. Conformational fluctuations are also calculated from the second derivative matrix obtained at the respective minimum energy conformations. Appreciable conformational changes upon chemical modification are observed only in the vicinity of the site of the modification. The nuclear magnetic resonance data on both BPTI and the modified BPTI are analyzed to compare with the calculated conformational changes upon chemical modification. Good correlations are found between the theoretically predicted and experimentally deduced conformational changes. The theoretical method employed here has a general application for the calculation of small conformational changes of globular proteins upon their chemical modification or an amino acid substitution.
D007611:Aprotinin; D009682:Magnetic Resonance Spectroscopy; D008433:Mathematics; D008958:Models, Molecular; D011487:Protein Conformation
D007611:Aprotinin