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Letter from Eddie Hughes to Linus Pauling. May 8, 1952.
Hughes writes to provide further details of the Royal Society proteins meeting that Pauling missed as a result of his passport difficulties. In it, Hughes details the specifics of work that European scientists have been conducting that is relevant to the Caltech group's proteins research and provides his thoughts on how this new data might impact the model that Pauling has been developing of the alpha-helix.

Transcript

THE UNIVERSITY

LEEDS 2

Dear Professor Pauling:

Since returning to Leeds I have received your letter from New York including the copy sent care of Kathleen. I am sorry the time for discussion was so restricted, for there were many things that could have been said if there had been time. Bob took notes on all the papers and will no doubt report them to you. I will at this time only mention the synthetic polypeptide work, as it is nearer to my own line of work. Except that I will say that the papers presented by Bragg and Perutz were substantially what they told me at Edinburgh a month ago and already sent to you in my letter last month. They have now fixed the sign choice for two of the seven layers so there are only five left before they can prepare a Fourier projection. I will also add that Astbury and his people are saying that everyone familiar with the field is sure that the 5.1 Å reflection of alpha keratin is a true meridional spot and not a doublet- and that they doubt if the Lotmar-Picken material is alpha keratin or even a protein. They express the same doubt over the fibrin for which they sent you pictures. These are matters that can be settled only by more experiments.

Bamford and Co. restated their criticisms of the March 1 Nature paper with the new point that they now believe their pictures are best fitted by a cell with co = 43.2 Å. This makes the old 5th layer now the 8th and all layers are given new indices which are the closest possible to 8/5 times the old indices. They also state that there are definitely weak spots, four of them, not indexed by this cell and not compatible with hexagonal packing. There is also a streak which, if part of the alpha patter, will require doubling co to give 86.4 Å. They give the Perutz spacing as 1.50 and their value for the old co was 27.0. These are notably larger than Yakel’s values. Their pictures were made in a vacuum camera with monochromatized rays and silver was plated on the sample to give the silver pattern for calibration purposes. As I do not know what precautions Harry took with regard to calibration and film shrinkage I do not know what to say about these discrepancies. But I do note that harry said to me in a letter several months ago that there were some spots that didn’t seem to fit the cell. I discussed their remarks about the infrared results in my letter last month. These same remarks were made in part by some Englishman, whose name I didn’t catch, immediately after Bob’s brief rebuttal but when I wanted to amplify them Adrian turned the meeting over to Edsall for the final summary.

Since then I have considered the new indexing. It corresponds to twenty-nine residues in eight turns. Upon applying the Cochrane-Vand formula one finds that for the layer lines observed the Bessel function orders are exactly those found for the old indexing while for the missing layers the orders are equal to or greater than those for the old indexing. A twenty-nine residue helix can’t have hexagonal symmetry. The cell might be orthorhombic with axial ratios almost exactly corresponding to hexagonal packing but with the C centering not exactly obeyed. The strong spots would then have spacings fitting a hexagonal cell but there could be some weak ones not permitted by a hexagonal cell. If at the same time the over all scale is nearer to Harry’s determination than to theirs, the density would fit and there is no argument against the alpha helix.

Checking over the above calculations suggested another interesting point to me. Yesterday I calculated the Fourier transform of a spiral of atoms with no true repeat. I assumed a fixed pitch p per atom and P per turn and assumed a large number of turns. By this time I was not surprised to find that

Even with no repeat a helix gives discrete layer lines. But in general there is no constant single layerline spacing. The structure factor equation (per atom) is like that given by Cochrane with the conditional equation being

P(ζ - k/P ) = m

where m is any integer, k is the order of the Bessel function involved and ζ is the reciprocal lattice coordinate parallel to the axis. This rearranges to

ζ = m/p + k/P

Thus for Bessel functions of a given order there is a system of layer lines with separation l/p . But with m constant one gets a system with separation l/P on which the Bessel function order increases by one between layer lines. If p and P have a l. c. m. c such that c = ap = bP with a and b integers, then

ζ = ma/c + kb/c = l/c,

which is the case for a true repeat co , l being the layer line index. This is the case discussed by Cochrane.

If one knows approximate values for p and P one can from the observed ζ values find the m and k values for each observed layer, making use of the fact pointed out by Cochrane that the order k must be low. One can then carry out at least squares determination of p and P . Bamford’s data in Nature are given as spacings rather than as layer line separations. I have converted them to ζ values using a slightly smaller value of ao than they give, a change suggested by the agreement between calculated and observed values on the equator. They give no numerical data at all for two very weak layers. From an analysis as outlined above I get p = 1.499 and P = 5.42 . . I suggest that such a calculation should be made for Harry’s data after the calibration has been checked if that appears necessary.

I believe it was Dorothy Crowfoot who mentioned to me at Oxford in February that rotation pictures about a certain axis of a certain protein- I think she said Bernal’s ribonuclease- has this characteristic appearance. She asked at that time what it might mean. From the above it appears that it might mean there are spirals parallel to the axis with P much larger than p so that as you go up the layer line series the Bessel function order increases regularly and one must go farther and farther from the meridian to find spots.

I am still thinking about all this and may send a note to Nature.

We are expecting Bijvoet here next week and Kratky near the end of the month. The Corey’s will arrive about the time Bijvoet leaves. They are driving a rented car and left London yesterday for Oxford and Cambridge.

I suppose you will have heard of the letter Sir Robert Robinson wrote to the Times Monday. People here are generally baffled or angry or both about the State Department’s action. Kathleen told me that one of her colleagues said that any day now he would expect a modern Mayflower bringing back persecuted Americans to England. He overlooked the fact that modern Mayflowers require passports. If you are planning to take any action involving legal or other expense I would be glad to send a check to help and will do anything else I can to be of assistance.

With regard to my appointment- if I understand the implications I think we would rather stay on the nine month basis. All of our relatives are either in the Eastern United States or in Europe. We would therefore like to be free to leave about one summer in three to come over here. These visits would be arranged at the times of the International Union Congresses or some other equally important scientific meeting but would still be primarily visiting. Otherwise we would remain in Pasadena most of the summer-so what we need is to alternate, two years on full time basis and one year on nine months basis but that of course is too fancy an arrangement. We do not think at the moment that we need the extra money and would rather feel free to be away, as outlined above, if you do not think it contrary to the good of the Division.

Best wishes and regards to you and Mrs. Pauling.

Sincerely,

P. S.

I wish also to raise a question regarding Figure 3 of your MS and the statement on page 9 that Harry has calculated the intensities for the fifth layer. The only reference is to the published work of Cochrane Crick and Vand which I have not seen (i.e., their forthcoming Acta paper. I do not know what they give but the full structure factor for one residue is given by

[lengthy handwritten equation]

where ξ, ζ, α are reciprocal space cylindrical coordinates, rj, xj and βj are the cylindrical coordinates of the jth atom of the residue relative to some origin in the helix, k is the order of Bessel function and the equation given above relates ζ , k, p, P and the arbitrary integer m. Now to get a proper Figure 3 one would split this structure factor equation into real and imaginary parts, sum over the j’s with appropriate coordinates for each atom, square and add the two squares and then average over alpha. As nearly as I can tell Figure 3 was actually computed for just one atom and accordingly represents only approximately and only near the meridian the places where the intensity can be large and in particular where it must be zero. Because of the Bessel function argument I feel that Figure 3 is useful only at small values of the argument and then only for showing where the intensity must be zero. I also wonder if Harry went through this full complicated process, taking into account also the position of the helix in the cell?

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