Reprinted from TIIE REVIEW OF SCIENTIFIC INSTKUMENTS, Vol. Z-1, No. 8, 621-627, August, 1953
                            Printed in U. S. A.

Molecular Models of Amino Acids, Peptides, and Proteins

                ROBERT B. COREY AND LINUS PAULING
Gales altd Cm& Laboraiories of Chemistry,* California Instilule of Technology, Pasadena, Californiai
                (Received August 25, 1952)

A set of accurate scale models has been developed for use in studies of the structures of amino acids,
peptides, and proteins. Models representing atoms or groups of atoms built from hard wood to the scale
1 in. = 1A are connected by a clamping device which maintains desired molecular configurations. These
accurate models have been used as substitutes for calculation in investigations of the probable configuration
of the polypeptide chain in proteins. Analogous models constructed of rubber-like plastic to the scale
1 in. = 2.4 and connected by snap fasteners are designed for qualitative studies of protein structure.

INTRODUCTION

F OR several years we have been working at the Cali-
  fornia Institute of Technology on the development
of scale models for representing the molecules of amino
acids and related compounds as an aid in our attack on
the problems of the structure of proteins. The develop-
ment of these models has closely paralleled our x-ray dif-
fraction studies of amino acids, peptides, and proteins.
Our first models were constructed in accordance with
the dimensions experimentally obtained from complete
and accurate determinations of the structures of amino

FIG. 1. An exploded view of the device used for clamping the
atom models rigidly to the connecting cylindrical shafts. The
threaded bushing B imbedded in the atom (see Fig. 2) is inter-
sected on one side by a hole drilled in the atom and containing
the two clamping (C, C') jaws. The latter are cut away so as
to grip firmly the &-in. steel shaft S (see Fig. 3 and following
figures).

acids. They were progressively revised and extended as
more accurate data from peptides and additional amino
acids became available. Recently we have been engaged
in a study of the structure of proteins which has led us
to propose several new configurations of the polypep-
tide chain. Because these proposed configurations are
explicitly described in terms of atomic coordinates,
their occurrence in proteins can be tested by com-

* Contribution No. 1731.
t Aided by a grant from the National Foundation for Infantile
Paralysis,

parison of their theoretically calculated x-ray diffrac-
tion patterns with those derived experimentally from
the proteins themselves.' In this study our molecular
models have been of great assistance, especially in the
recognition of sterically probable configurations of the
polypeptide chain and the rejection of sterically im-
probable ones.2

With the continued refinement of x-ray diffraction
measurements and the accumulation of new structural
data, future revision of some dimensions will doubtless
be desirable and models of additional atoms and radi-
cals will be designed and constructed. Nevertheless the
demonstrated usefulness of these models in their
present form seems to justify a description of them at
this time.

   REQUIREMENTS AND SPECIFICATIONS
In models designed for studying probable molecular
configuration and intermolecular packing the van der

L DIAMETER  OF BALL = 2.50"

FIG. 2. A drawing of the tetrahedral carbon atom. The positions
of two of the four clamps and of fiducial marks are indicated. Each
face is 0.77 in. from center of ball. The ends of the steel bushings
are shown in each face.

r Pauling, Corey, and Branson, Proc. Natl. Acad. Sci. U. S. 3!,
205 (1951). L. Pauling and R. B. Corey, Proc. Natl. Acad. Scl.
U. S. 37, 235, 241, 251, 256, 261, 272, 282 (1951).
s L. Pauling and R. B. Corey, Proc. Natl. Acad. Sci. U. S. 37,729
(1951); Proc. Natl. Acad. Sci. U. S. 38, 86 (1952).

621


622                   R. B.  COREY A I VD L.  PAULING

Waals radii of the atoms should conform to the inter-
molecular distances found in crystals and in noncrystal-
line solids rather than to gas collison radii or even
smaller radii commonly used in models of organic mole-
cules. Intramolecular interferences between atoms at-
tached to the same atom or group of atoms must be
avoided unless there is experimental or theoretical
justification for believing that the interferences occur.
If the models are intended for use as a substitute for

calculation in the examination of structures, they must
be accurately built and capable of retaining their bond
angles and other configurational features without de-
formation ; the scale should be conveniently large to
permit easy handling and to allow angles and distances
to be measured with satisfactory precision. In order to
meet even these minimum requirements, many com-
promises were found to be necessary.

The models are made of hard wood to the scale, 1 in.
= 1 A. Van der Waals radii, bond radii, and bond angles
have the dimensions generally found in crystals of
ammo acids, peptides and other organic compounds.
Atoms or assemblies of atoms, as the benzene nucleus
and amide group, are joined together by means of short

FIG. 3(a). A drawing
of the double-bonded
carbon atom. In the in-
terest of clarity, only
one clamp is shown in
the view along the
double-bond direction.

FIG. 3(b). A drawing
of the aromatic carbon
atom. Six atoms are
fastened together per-
manently to form the
benzene nucleus.

STUD

8 1.03"

L DIAMETER OF BALL = 2.50"

FIG. 4. A drawing of the tetrahedral positively charged nitrogen
atom. For representing the neutral atom, the adapter applies an
appropriate van der Waals radius to one of the bond positions.

pieces of &-in. steel rod which fit into steel bushings
imbedded in the atoms. For rigidly fixing the relative
orientation of atoms around a bond, the bushings are
locked on the rod in any desired position by means of
clamping fixtures also built into the atom. An exploded
assembly drawing of the steel stud, bushing, and clamp-
ing device used to connect the atoms is shown in Fig. 1.
Models of carbon, nitrogen, oxygen, and hydrogen
atoms, and of typical assemblies are described in the
following paragraphs.

The Carbon Atom

A drawing of the tetrahedral carbon atom is shown
in Fig. 2. The bond radius is 0.77 in. Since the tetrahe-
dral carbon atom is entirely surrounded by bonded
atoms and so in general makes no van der Waals con-


MOLECULAR MODELS                      623

( a)

(b)

FIG. 5. Drawings of the (a) single-bonded and
  (b) double-bonded oxygen atom.

!E .

tacts, the radius of the ball (1.25 in.) bears no relation-
ship to the van der Waals radius (1.5 A) of carbon, but
was selected for reasons of convenience. When this atom
is incorporated in the polypeptide chain, fiduciary
marks (numbered 0, 1, 2, 3, 4, 5) 60" apart around the
edges of two faces register with marks on the amide
group for indicating the orientation around the single
bond.

A double-bonded carbon atom is shown in Fig. 3a.
The single and double bond radii are 0.77 and 0.67 in.,
respectively. In the nonbonded direction the radius of
the ball (1 SO in.) corresponds to the van der Waals
radius of carbon. The slot on the double-bond face re-
ceives a key to determine the orientation and prevent
rotation around the double bond.

Aromatic carbon atoms (Fig. 3b) are built into per-
manent six-membered benzene nuclei. The single bond

1.10" RADIUS

FIG. 6. A drawing of
the hydrogen atom.

radius and the carbon-carbon distance within the ring
are 0.77 in. and 1.39 in., respectively.

The Nitrogen Atom

The positively charged tetrahedral nitrogen atom is
shown in Fig. 4. It can be transformed into the neutral
atom by the use of an adapter which applies an ap-
propriate van der Waals radius to one of the four bond
positions. The amide nitrogen atom is described below
as part of the amide group.

The Oxygen Atom

The dimensions of the single- and double-bonded
oxygen atoms are shown in Fig. 5. The latter is relieved

ADIUS -- 1.40"
DIAMETER OF
BALL = 2.00"

SPL,; R,NG\bTHREADED STUD
STEEL SPRING

200
A!-

!  /
    /
&
--

    0a

u

FIG. 7. A drawing of the hydrogen-bonding hydrogen atom
showing how the H. . .O vector may be inclined at angles of from
0' to 20" to the N-H bond direction by rotation of one section
of the model relative to the other.


624

R. IS.

WOOD DOWEL

0
  0

      (cl

OF
1.35"

COREY AND L. PAULING

(b)

Cd)

on opposite sides to permit the near intramolecular ap-
proach of atoms bonded to the atom to which the oxy-
gen is attached.

The Hydrogen Atom

A drawing of a model of the hydrogen atom repre-
senting a bond radius of O..3OA and a van der Waals
radius of 1.2OA are shown in Fig. 6. At large angles to
the direction of the bond, the van der Waals radius is

FIG. 8. A drawing of the amide
group showing the dimensions of
the (a) nitrogen, (b) carbon, and
(c) oxygen atoms and (d) the
assembled group. The three atoms
are glued together to form a rigid
unit.

somewhat reduced to permit closer intramolecular ap-
proach of atoms.

The formation of N-H. + .O hydrogen bonds is an
important factor governing the arrangement of the
molecule in crystals of amino acids and simple peptides.
In proteins the configuration of the molecules and their
specific spatial arrangements in crystals and fibers is
directly related to their peculiar capacities for hydrogen
bond formation. Our crystal structure studies of amino


MOLECULAR MODELS                     62.5

FIG. 9. A photograph of a scale model of one molecular layer
in a crystal of N-acetylglycine, showing how the molecules are
held together by O-H . . .O and N-H.. .O hydrogen bonds.

acids and peptides have shown that in N-H.. -0
bonds the distance between the nitrogen and oxygen
atoms generally falls within the range 2.79f0.12 A and
the Ha . .O vector usually makes an angle of less than
20" with the probable direction of the N-H bond.
These dimensions have been incorporated in a model of
the hydrogen-bonding hydrogen atom illustrated in
Fig. 7. The model is composed of two sections held
together by a spring snap ring. When a model of an
oxygen atom rests in the depression its center is ap-
proximately 2.70 in. from the center of the nitrogen
atom to which the hydrogen atom is attached. Rotation
of the two parts of the hydrogen atom relative to one
another inclines the H. . .O vector from 0" to 20" with
respect to the direction of the N-H bond. The angle of
inclination can be read on a scale.

       The Amide Group
The polypeptide chain

HRI 9 7 Hj& 0
t I          \. "
' \ /y ,N, lb\
N f C' N ,%
A R,k 6  $/

may be regarded as a series of tetrahedral carbon atoms
(to each of which are attached a hydrogen atom and a
side chain R) connected by amide groups. The amide

   9
group, , N )% , is planar or very close to planar

because of the resonance of the double bond between
the carbon-oxygen and the carbon-nitrogen positions.
A model of the amide group is shown in Fig. 8. The
bond lengths represented are doubtless close to those
which occur in peptides and proteins. The bond angles
around the nitrogen and the carbon atoms are probably
not so accurate, both because experimental data are
still insufficient to establish them with certainty and
because compromises have been made to increase the
simplicity and to extend the usefulness of the models.
It is unlikely that any of these angles differs by greater
than 3" from their average value in proteins.

The Side Chains

Many of the side chains of proteins can be constructed
from the models for carbon, hydrogen, oxygen, and

FIG. 10. A photograph of a model of the polypeptide chain in
the configuration of the (Y helix, illustrating hydrogen bonding
between adjacent turns of the helix.


626                     R. B.  COREY AND L. PAULING

nitrogen atoms already described. The benzene nucleus
of phenylalanine and tyrosine is made up as a single
permanent unit rather than assembled from separate
pieces representing the aromatic carbon atom. Because
of the rigidity and close tolerances of the bond angles,
it is necessary to use a slight variant of the tetrahedral
carbon atom for the construction of a model of the five
membered ring of proline representing the configuration
found in crystals.3 We have not yet built models of the
special groups in histidine, arginine, and tryptophan,
the dimensions of which have yet to be established by
x-ray analysis.

APPLICATIONS OF THE MODELS

A typical example of the use of the models to repre-
sent the crystal structure of an amino acid or simple
peptide is shown in Fig. 9, which is a photograph of a
scale reproduction of one molecular layer in the crystal
of N-acetylglycine. The molecules are planar and are
held together by N - H. . -0 and 0-H.. -0 hydrogen
bonds; the only other intermolecular contacts within
the layer are between the hydrogen atoms of the CH,
and CHa groups.

FIG. 11. A photograph of a suspension device for use in study-
  ing the packing of contiguous polypeptide chains.
a J. Donohue and K. N. Trueblood, Acta Cryst. 5, 414, 419
(1952).

A model of the polypeptide chain in the form of the
3.7-residue helix is shown in Fig. 10. There is strong
evidence that this configuration is present in many
proteins and synthetic peptides having the a-keratin
structure.' The helix shown in Fig. 10 represents a chain
of polyglycine. In proteins containing amino acids other
than glycine the side chains occupy one of the two
hydrogen positions on the a-carbon atom. For investi-
gating the possible configurations of polypeptide chains
and especially for studying the packing of chains in
conformity with the x-ray diffraction data obtained
from proteins, the device illustrated in Fig. 11 has been
found to be extremely useful.

FIG. 12. A photograph comparing the dimensions of a half-
scale plastic model of phenylalanylalanylalanine with those of a
full-scale (1 in. = 1A) wooden model.

SMALL-SCALE PLASTIC MODELS

Because of their weight and bulk, models built to the
scale 1 in. = 1 A are inconvenient for work with large
molecules or long polypeptide chains. We have therefore
built a complementary set of models on half this scale.
At first, they too were made of wood; because of their
small size and different purpose they were fastened to-
gether by snap fasteners instead of internal clamps.
These smaller models were indeed very useful. Their
principal disadvantages were the high cost of manu-
facture and the lack of friction between bonded atoms
which permitted them to rotate so easily around the
bonds that particular molecular configurations were not


MOLECULAR MODELS                     627

well maintained. We have now greatly improved these
models in both respects by casting them from colored,
rubber-like vinyl plastic. The friction between the
bonded faces reduces the freedom of rotation around the
bonds, but permits the molecular configuration to be
altered easily. The slight deformation which is possible
with the plastic models makes them more adaptable
to structures with bond angles or bond lengths differing
slightly from the normal values. Advantage is taken of
this deformability in the design of a simple hydrogen-
bond hydrogen atom in which this property of the
plastic renders unnecessary the elaborate two-piece
construction used in-the wooden models.

These smaller-scale models are very useful for quali-
tative studies of molecular configuration and packing,
but they cannot be used as a substitute for calculations.
They are therefore complementary to the more precise
large-scale models, and are not capable of doing the work
for which the larger models were expressly designed.

Neither the large nor the small-scale models are com-
mercially available. Models of the peptide phenylalanyl-
alanylalanine constructed on the large and the small
scale are contrasted in Fig. 12.

ACKNOWLEDGMENTS

The development of the molecular models described
in this paper has been a collaborative effort in which
many members of the staff of the California Institute
of Technology have participated. We are especially
grateful to Roger Hayward and William W. Schuelke
for their ingenious solutions of many of the problems of
design and construction, to Delmer D. Dill for his ex-
cellent workmanship, and to many members of the In-
stitute faculty for their criticisms and suggestions.

For five years this work was aided by a grant from
the National Foundation for Infantile Paralysis; more
recently it has been aided by a grant from the National
Institutes of Health, U. S. Public Health Service.