John Cowdery Kendrew helped establish how X-ray crystallography can reveal the three-dimensional arrangement of a protein. Nobel's primary nomination archive names John Cowdery Kendrew, also identifying J. C. Kendrew in its award-sharing comment.^[ref]

His team's1960 myoglobin paper presented a Fourier analysis at2-angstrom resolution. Its opening recalls how earlier phase determination compared native crystals with heavy-atom derivatives containing localized mercury or gold sites. Such comparisons supply information missing from a simple measurement of diffraction intensity.^[ref]

An original one-dimensional example explains that phase problem. Write a periodic electron density using Fourier series coefficients

F_{k}

. The two positive densities

ρ_{+} (x) = 3 + cos x + \frac{1}{2} cos 2 x, ρ_{-} (x) = 3 + cos x - \frac{1}{2} cos 2 x

(1)

have

F_{0} = 3

F_{\pm 1} = 1/2

and

F_{\pm 2} = \pm 1/4

, with the final sign distinguishing them. Their squared coefficient magnitudes are identical:9 for mode zero,1/4 for modes

\pm 1

and1/16 for modes

\pm 2

. The relative phase of the second harmonic has changed while the first harmonic is fixed. Thus equal intensities need not identify one density.

Figure 1.
Different positive model densities can have the same squared Fourier coefficient magnitudes
. Original one-dimensional mathematical example, not a measured protein diffraction pattern. The sign of the second harmonic differs while the first harmonic is unchanged, so the density shapes differ despite equal mode intensities. **Details**.

The myoglobin experiment was more demanding than this toy calculation, but the distinction motivates its chemical strategy: modifying crystals at known heavy-atom sites changes their scattering in a way that constrains phase information. Reconstructing an electron density map therefore requires both measured diffraction and a justified phase-determination method, rather than treating the recorded spots as a direct photograph of the molecule.

Figure 2.
John Kendrew, named portrait from the MRC Laboratory of Molecular Biology Image Bank
.

Work by J. C. Kendrew

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 Tagged

Structure of Myoglobin: A Three-Dimensional Fourier Synthesis at 2 Å. Resolution by J. C. Kendrew and others

Chris Oubridge (1966-2020)

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Chris Oubridge investigated the structural basis of RNA splicing and RNA recognition by proteins. The original 1994 publisher record names him as first author of the U1A protein–RNA hairpin structure previously cited under C. Oubridge.^[ref] His institutional obituary records 1966–2020 and describes his contributions to spliceosome structural studies.^[ref]

For an original affinity example, suppose changing a loop raises a measured dissociation constant from

10

100 nM

. At 298 kelvin, the corresponding change in standard binding Gibbs free energy is

ΔΔ G^{\circ} = RT ln \frac{K _{d, 2}}{K _{d, 1}} = RT ln 10 \approx 5.7 kJ mo l^{- 1},

(1)

where

R

is the molar gas constant. These are stipulated values, not measurements from the 1994 paper. A structure can motivate which contacts to test, while an independent binding affinity measurement establishes the net energetic effect; counting visible contacts alone does not supply that effect.

Oubridge also shared first authorship of the 2009 U1 snRNP functional-core structure, connecting the study of an individual recognition domain with the arrangement of RNA and proteins in a larger assembly.^[ref]