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A pseudo‐particle approach for studying protein‐ligand models truncated to their active sites
Author(s) -
Kern Petra,
Brunne Roger M.,
Rognan Didier,
Folkers Gerd
Publication year - 1996
Publication title -
biopolymers
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/(sici)1097-0282(199605)38:5<619::aid-bip7>3.0.co;2-v
Subject(s) - chemistry , active site , ligand (biochemistry) , molecular dynamics , hydrogen bond , hiv 1 protease , folding (dsp implementation) , protein ligand , binding site , homology modeling , crystallography , biophysics , molecule , protease , computational chemistry , biochemistry , enzyme , biology , receptor , organic chemistry , electrical engineering , engineering
A molecular dynamics method has been developed to describe the structural and dynamic properties of protein‐ligand complexes that are truncated to their active sites. The active site is comprised of the ligand and discontinuous, positionally unrestrained peptide chains. This truncated active‐site complex is surrounded by big unspecific pseudo‐particles representing the complete protein and the solvent. Thus, knowledge of the folding of the outer parts of the protein is not required, and the method can be applied to protein models, derived from homology modeling. The method has been tested using ligand complexes of adenylate kinase, retinol binding protein, HIV‐1 protease, and human leucocyte antigen. Comparisons with their crystal structures and with results from time‐demanding simulations of the whole complexes in explicit water solvent show that the ligand binding properties are conserved. Most of the hydrogen bonds between the ligand and the active‐site residues are reproduced and, furthermore, the simulation time is reduced. © 1996 John Wiley & Sons, Inc.