Distance geometry and related methods for protein structure determination from NMR data

Abstract

The method of choice to reveal the conformation of protein molecules in atomic detail has been X-ray single-crystal analysis. Since the first structural analysis of diffraction patterns, computer calculations have been an important tool in these studies (Blundell & Johnson, 1976). As is described by Sheldrick (1985), it has been taken for granted that a necessary first step in the determination of a protein structure would be writing computer programs to fit structure factors. In contrast the combined use of the structural analysis of NMR data and computer calculations has been quite limited. An early attempt of such structural calculations was the quantitative determination of mononucleotide conformations in solution using lanthanide ion shifts (Barry et al. 1971).

Conformations of biopolymers in the gas phase: a new mass spectrometric method

“…For polypeptides and proteins, the overwhelming emphasis has been on determining condensed phase structures, primarily by x-ray diffraction [1] and multidimensional nuclear magnetic resonance (NMR) [2]. The historical reasons for this preference are twofold: first the condensed phase allows much greater molecular density and hence larger signals and second, it is presumed that such condensed-phase structures bear resemblance to the biologically active form of the molecule.…”

Automated Assignment of Simulated and Experimental NOESY Spectra of Proteins by Feedback Filtering and Self-correcting Distance Geometry

“…These methods use standard stereochemical properties of the amino acid residues and hard sphere models for non-bonded interactions. In the past the metric matrix distance geometry (Havel et al, 1983;Kuntz et al, 1989) and the variable target function method in torsion angles (Braun & Gō , 1985;Braun, 1987;Gü ntert et al, 1991), both of them implemented in a variety of different programs, were mainly used. Due to spin diffusion and flexibility of the protein, the distance constraints were usually estimated only as upper limits, which form a correct but incomplete data set.…”

“…No initial preliminary three-dimensional structure is needed, which might bias the assignments in the first cycle. This is in contrast to the standard procedure, in which one first determines the global fold using only unambiguous cross peaks in a bootstrap technique (Braun, 1987;Gü ntert et al, 1993;Meadows et al, 1994). Our method has to overcome two potential difficulties: that the three-dimensional protein structures might never fold into compact structures or that they might converge towards a wrong fold ''confirming'' wrong Figure 9.…”

Pattern recognition and self‐correcting distance geometry calculations applied to myohemerythrin

“…These reference atoms are Q" for Gly, Q"' for Ala, Ca for Ser, Asn, Asp, Thr and Cys, Cy for Pro, Gln, Glu, Met, Trp and His, Cyl for Ile, QQG for Val, Cs for Lys and Arg, QQD for Leu, and QR for Phe and Tyr. The reference atoms Q are pseudo atoms as used by distance geometry calculations from NMR data [24]. Between all residues of the 'outside' list, separated in the sequence by more than 10 residues, a lower bound of 15 A for the distance between the reference atoms are used.…”

“…Analogous expressions are used for the lower bound. The contributions from the dihedral angles and the van der Waals repulsion are treated as usual with distance geometry calculations in torsion angles [24]. Calculations are done including all heavy atoms of myohemerythrin.…”