Determination of three‐dimensional structures of proteins from interproton distance data by dynamical simulated annealing from a random array of atoms Circumventing problems associated with folding

FEBS Letters

Clore, G.Marius¹  Nilges, Michael¹  Gronenborn, Angela M.² 

[1] Max-Planck-Institut für Biochemie, D-8033 Martinsried bei München, FRG;Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA

关键词: NMR;    Protein structure;    Interproton distance;    Dynamical simulated annealing;    NMR;    nuclear magnetic resonance;    NOE;    nuclear Overhauser effect;    RMS;    root mean square;   

DOI  :  10.1016/0014-5793(88)80559-3

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

A new real space method, based on the principles of simulated annealing, is presented for determining protein structures on the basis of interproton distance restraints derived from NMR data. The method circumvents the folding problem associated with all real space methods described to date, by starting from a completely random array of atoms and introducing the force constants for the covalent, interproton distance and repulsive van der Waals terms in the target function appropriately. The system is simulated at high temperature by solving Newton's equations of motion. As the values of all force constants are very low during the early stages of the simulation, energy barriers between different folds of the protein can be overcome, and the global minimum of the target function is reliably located. Further, because the atoms are initially only weakly coupled, they can move essentially independently to satisfy the restraints. The method is illustrated using two examples of small proteins, namely crambin (46 residues) and potato carboxypeptidase inhibitor (39 residues).

【 授权许可】

Unknown