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A specific inhibitor design approach by means of molecular dynamics calculation for porcine pancreatic elastase
Author(s) -
Fujita T.
Publication year - 1987
Publication title -
journal of computational chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.907
H-Index - 188
eISSN - 1096-987X
pISSN - 0192-8651
DOI - 10.1002/jcc.540080509
Subject(s) - tripeptide , chemistry , hydrogen bond , radius of gyration , molecular dynamics , intermolecular force , ligand (biochemistry) , crystallography , pancreatic elastase , dipeptide , molecule , elastase , computational chemistry , stereochemistry , peptide , enzyme , organic chemistry , biochemistry , receptor , polymer
A 27‐picosecond (ps) molecular dynamics calculation has been carried out for the 1:2 enzyme‐ligand complex between porcine pancreatic elastase (PPE) and acetyl‐alanine‐proline‐alanine (APA). A data analysis has been carried out using a total of 450 structures. During the simulation, the root‐mean‐square fluctuations (RMSF) increased compared with the x‐ray data. Some differences of the hydrogen bond arrangement in the MD average structures are found especially for SER 195, suggesting the fluctuations of the ligand molecules. The radius of gyration decreased a little during the simulation. Although intermolecular hydrogen bonds between two substrates (APA1 and APA2) has not been found by a 1.65‐Å high‐resolution x‐ray diffraction study, the MD calculation showed the intermolecular hydrogen bond between them to be 3.2 Å. The extended active site of PPE is so wide compared with the size of a tripeptide that such a hydrogen‐bound hexapeptide can be more specific than tripeptides, which is consistent with the kinetic data previously reported.