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Molecular dynamics study of calbindin D 9k in the apo and singly and doubly calcium‐loaded states
Author(s) -
Marchand Sylvie,
Roux Benoît
Publication year - 1998
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/(sici)1097-0134(19981101)33:2<265::aid-prot10>3.0.co;2-i
Subject(s) - chemistry , molecular dynamics , hydrogen bond , crystallography , calcium binding protein , calcium , molecule , nuclear magnetic resonance spectroscopy , relaxation (psychology) , coordination sphere , solid state nuclear magnetic resonance , side chain , chemical physics , computational chemistry , stereochemistry , nuclear magnetic resonance , crystal structure , physics , polymer , psychology , social psychology , organic chemistry
Molecular dynamics simulations based on detailed atomic models are used to examine the structure and dynamics of calbindin D 9k , a protein possessing a pair of EF‐hands able to bind two calcium ions in a cooperative fashion. Trajectories for the apo and singly (in the C‐terminal binding site) and doubly loaded structures are generated and analyzed. Each system is solvated in a 27 Å radius sphere of 2,285 explicit water molecules. The influence of the remaining bulk is incorporated through a stochastic boundary potential including a solvent reaction field. Long‐range electrostatic interactions are treated with a special method and are not truncated. The average structural and dynamic properties upon calcium binding are studied at the atomic level to gain insight into the cooperative interactions between the two binding sites. Results from the trajectories are compared with data from nuclear magnetic resonance (NMR) spectroscopy and X‐ray crystallography. NMR 15 N and 13 C α backbone relaxation order parameters and crystallographic B ‐factors are calculated. Generally, there is a good qualitative agreement between calculated and observed properties. Results confirm that the doubly loaded state is closer, both structurally and dynamically, to the singly loaded state than either of these is to the apo state. It is observed that both hydrogen bonding and the packing of nonpolar side chains contribute to the coupling between the calcium binding sites. Two backbone‐to‐backbone hydrogen bonds linking the calcium‐binding EF‐hands (Leu23‐O · · · HN‐Val61 and Val61‐O · · · HN‐Leu23) are sensitive to the state of occupancy. Residues Leu23 and Val61 exhibit the smallest rms fluctuations of the entire protein in the D state. In addition, the van der Waals interaction of Val61 with the rest of the protein varies with the calcium‐binding state. Proteins 33:265–284, 1998. © 1998 Wiley‐Liss, Inc.