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Simulated annealing with restrained molecular dynamics using CONGEN: Energy refinement of the NMR solution structures of epidermal and type‐ α transforming growth factors
Author(s) -
Tejero Roberto,
BassolinoKlimas Donna,
Bruccoleri Robert E.,
Montelione Gaetano T.
Publication year - 1996
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1002/pro.5560050403
Subject(s) - simulated annealing , maxima and minima , molecular dynamics , weighting , chemistry , nuclear magnetic resonance spectroscopy , biological system , crystallography , annealing (glass) , physics , chemical physics , computational chemistry , algorithm , computer science , stereochemistry , mathematics , thermodynamics , mathematical analysis , acoustics , biology
The new functionality of the program CONGEN (Bruccoleri RE, Karplus M, 1987, Biopolymers 26 :137–168; Bassolino‐Klimas D et al., 1996, Protein Sci 5 :593–603) has been applied for energy refinement of two previously determined solution NMR structures, murine epidermal growth factor (mEGF) and human type‐ α transforming growth factor (hTGF α ). A summary of considerations used in converting experimental NMR data into distance constraints for CONGEN is presented. A general protocol for simulated annealing with restrained molecular dynamics is applied to generate NMR solution structures using CONGEN together with real experimental NMR data. A total of 730 NMR‐derived constraints for mEGF and 424 NMR‐derived constraints for hTGF α were used in these energy‐refinement calculations. Different weighting schemes and starting conformations were studied to check and/or improve the sampling of the low‐energy conformational space that is consistent with all constraints. The results demonstrate that loosened (i.e., “relaxed”) sets of the EGF and hTGF α internuclear distance constraints allow molecules to overcome local minima in the search for a global minimum with respect to both distance restraints and conformational energy. The resulting energy‐refined structures of mEGF and hTGF α are compared with structures determined previously and with structures of homologous proteins determined by NMR and X‐ray crystallography.