precision space-filling atomic models

15
BIOPOLYMERS VOL. 3, PP. 665-679 (1965) The Editorial Board wishes periodically to inform the scientific community of innovations and developments that can sub- stantially aid the scientist in his research. W e believe that the development of the Corey-Pauling-Koltun Atomic Models represents just such an instance. W e therefore are pleased to publish the information as a supplement to the standard presen- tations of original research work. Precision Space-Filling Atomic Models* WALTER L. KOLTUN, t Program Director, Molecular Biology Section, National Science Foundatim, Washingtm, D.C. Synopsis Shortly, lightweight, inexpensive, precision, space-filling atomic models particularly suitable for constructing macromolecules of biological interest will reach the scientific community. The availability of the models, the Corey-Pauling-Koltun, or C-P-K Models, will conclude a five-year program which haa involved the cooperative efforts of Federal agencies, scientific societies, and selected scientists. This paper describes the development of the program, details the contributions of the various groups and persons who have been involved, and discusses the technical characteristics of the models. THE NEED FOR MODELS Three-dimensional molecular models facilitate the study and visualiza- tion of the space relationships among constituent atoms of molecules and also help to determine possible molecular structures. During the lake 1950s, many scientists expressed increasing concern at the lack of accurate, inexpensive atomic and molecular models suitable for use in research and training in the biochemical and biophysical sciences. The need for such models has been clearly established.' Not only are molecular models necessary to the understanding of many theories of biological structure and function, but such models may also stimulate the development of new theories. Previously available space-filling atomic models have distinct deficiencies. Some utilize metal snaps which tend to open when large molecules are con- structed. They have little or no provision for flexibility or for varying bond angles and distances. They provide no means for representing the concept of * The Corey-Pauling-Koltun Models to construct macromolecules soon will be avail- able for research and teaching. t Present address: Massachusetts Institute of Technology, Cambridge, Massachu- setts. Copyright, W. L. Koltun, July 1965. 665

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Page 1: Precision space-filling atomic models

BIOPOLYMERS VOL. 3, PP. 665-679 (1965)

The Editorial Board wishes periodically to inform the scientific community of innovations and developments that can sub- stantially aid the scientist in his research. We believe that the development of the Corey-Pauling-Koltun Atomic Models represents just such an instance. We therefore are pleased to publish the information as a supplement to the standard presen- tations of original research work.

Precision Space-Filling Atomic Models*

WALTER L. KOLTUN, t Program Director, Molecular Biology Section, National Science Foundatim, Washingtm, D.C.

Synopsis Shortly, lightweight, inexpensive, precision, space-filling atomic models particularly

suitable for constructing macromolecules of biological interest will reach the scientific community. The availability of the models, the Corey-Pauling-Koltun, or C-P-K Models, will conclude a five-year program which haa involved the cooperative efforts of Federal agencies, scientific societies, and selected scientists. This paper describes the development of the program, details the contributions of the various groups and persons who have been involved, and discusses the technical characteristics of the models.

THE NEED FOR MODELS

Three-dimensional molecular models facilitate the study and visualiza- tion of the space relationships among constituent atoms of molecules and also help to determine possible molecular structures. During the lake 1950s, many scientists expressed increasing concern at the lack of accurate, inexpensive atomic and molecular models suitable for use in research and training in the biochemical and biophysical sciences. The need for such models has been clearly established.'

Not only are molecular models necessary to the understanding of many theories of biological structure and function, but such models may also stimulate the development of new theories.

Previously available space-filling atomic models have distinct deficiencies. Some utilize metal snaps which tend to open when large molecules are con- structed. They have little or no provision for flexibility or for varying bond angles and distances. They provide no means for representing the concept of

* The Corey-Pauling-Koltun Models to construct macromolecules soon will be avail- able for research and teaching.

t Present address: Massachusetts Institute of Technology, Cambridge, Massachu- setts.

Copyright, W. L. Koltun, July 1965.

665

Page 2: Precision space-filling atomic models

666 W. L. KOLTUN

rotational potential. They do not provide adequately for hydrogen bonding. Generally, the atomic units are so heavy that the connectors cannot hold a grouping of atoms in the correct spatial configuration. Those that are light in weight are not accurate enough to construct models of macro- molecules of research value. Finally, they are expensive, costing on the average, more than seventy-five cents per atom.

Because of the great need, in May 1960, the Biophysics and Biophysical Chemistry Study Section (BBCSS), of the National Institutes of Health (NIH), requested its Principal Consultant to convene an ad hoc committee to examine the problem and to report its findings to the Study Section.2 The committee was to determine suitable specifications and standards, to suggest methods of implementing its recommendations, and to provide continuing advice and assistance until improved models could be made available commercially.

DESIRABLE CHARACTERISTICS OF ATOMIC MODELS

At its initial meeting in Berkeley, California, July 1960, the committee unanimously agreed that since space-filling units, which give a graphic three-dimensional picture of the molecule, are the most commonly used and most urgently needed, all efforts should be directed to making these avail- able to the scientific c~mmunity.~

The committee established the following exacting criteria and desirable characteristies.

I . Dimensions. Bond angles and distances, and van der Waals radii should represent the latest known dimensions and enable a wide variety of commonly occurring molecules to be constructed. Bond angles should be accurate to within *0"30', covalent radii to within *0.01 A, and van der Waals radii to within 3~0.03 A.

2. Scale. The scale should be 1.25 cm./A. This scale is large enough to maintain accuracy, but small enough to keep production costs low. Without being cumbersome, this scale also affords reasonable size and suf- ficient detail for visual purposes. Thus a molecule 20 X 40 X 100 A. would be represented by a model 25 X 50 X 125 cm.

3. The units should be as light as possible, consistent with strength and other requirements.

4. Restricted Bond Rotation. Those atoms which have no rotation should be prevented from rotating. Bonds between tetrahedral carbon atoms and between digonal sulfur atoms should embody the concept of rotational potential, with hindered rotation.

5. Hydrogen Bond. The models should provide for hydrogen bonding which is so prevalent in bio-macromolecules.

6. A sufficient variety of atoms should be available to enable the construction of important biological molecules.

7. Special Atoms. Provision should be made for individuals to con- struct special atoms which may be important but which are not used suf-

Weight.

Types of Atoms.

Page 3: Precision space-filling atomic models

PRECISION SPACE-FILLING ATOMIC MODELS 667

ficiently to warrant mass production. These atoms must be usable and compatible with standard atoms in the set.

8. Connectors. Satisfactory connectors must (a ) prevent atoms from separating readily; (b) allow the bond angle to be varied up to *So with little or no loss in bond strength; ( c ) support the weight of a side chain grouping of approximately 50 atoms with less than 3" of horizontal angular deflection and hold such a grouping of atoms in the correct spatial con- figuration, i.e., have sufficient rotational friction to prevent the group from rotating due to its weight; and (d) allow bond distances to be shortened or lengthened, within reasonable limits.

The models should be constructed of suitable plastics and the average cost per atom should be about fifteen cents. This price assumed mass production and subsidy of expensive production molds by a Federal agency. However, the price was a wish and not a firm cost estimate.

During the following year the committee prepared specifications con- cerning the kinds of atoms to be made, their bond angles, and their covalent and van der Waals radii. The author designed lightweight, accurate atomic units and a new type of connector which prevents the atoms from separating readily. Since the key to satisfactory models lies in the con- nector and since the types of atoms to be fabricated depend on the ver- satility of the connector, the characteristics of the latter are discussed first.

9. Materials and Cost.

Connectors

Available models are inadequate largely because when there are sniall strains between connected atoms and the angles between them change even slightly, they part too readily. This is illustrated in Figure 1, curve A,

a

Fig. 1. The force holding atoms together, F, plotted against LY, the deviat.ion of the bond angle. Curve A illustrates the case in which faces of connected atoms touch each other. Curve B illustrates what is desirable.

F, is the straight pull force needed to separate atoms.

Page 4: Precision space-filling atomic models

668 W. L. KOLTUN

in which the force holding atoms together, F, is plotted against a, the devia- tion of the bond from linearity. In most if not all previous models, the faces of connected atoms touch one another. Consequently, as soon as a deviates from zero, the resulting lever action tends to pull out the connector, causing F to decrease markedly and the atoms to separate. Since strained bonds are inevitable when macromolecules are constructed, connections frequently fail.

Ideally, F should decrease only slightly as a increases, until a exceeds some desired limit, here chosen to be 8". Only then should F decrease rap- idly so that it is easy to pull atoms apart. Curve B illustrates this case.

( 0 ) f b )

Fig. 2. The socket ( a ) and standard connector (a).

Figure 2 shows the two components, socket (a) and standard connector (b), whose design characteristics meet the foregoing requirements. The connector is made of Texin, a polyurethane elastomer, durometer 95,6 a hard rubber-like material which is strong, resilient, and flexible in small diameters.

The connector snaps into a female socket (Fig. 2a), which is an integral part of the atom body. The socket and the connector are designed to achieve the three requirements stated above @a, b, and c) more or less independ- ently of one another. This is extremely important because it means that the optimum dimensions for each characteristic may be selected independ- ently, and with minimum compromise.

Requirement 8a, to prevent atoms from separating readily, is satisfied by selecting appropriate values of 0 and 0' (Fig. 2). With given materials for the connector and socket, the straight pull force needed to separate the atoms, F, in Figure 1, relates directly to the difference between 0' and 0. In the C-P-K Models these dimensions were selected to give a value of F, of 15-20 lb. This force is much too large for easy disassembling of atoms. The easiest way to separate atoms is to bend the connector until the atom faces touch. Continued bending takes advantage of the lever action and the atoms snap apart readily.6

Page 5: Precision space-filling atomic models

PRECISION SPACE-FILLING ATOMIC MODELS 669

--I k 0 . 0 2 8 in.

Fig. 3. Interfacial dimensions. The connector is omitted for clarity.

Requirement 8b, that the bond angle vary up to =t8" with little or no loss in bond strength, is met by slightly separating the faces of connected atoms, by constructing the faces with a slight angle, and by narrowing the central part of the connector, N, (Fig. 2b). The diameter of the neck, N, controls the flexibility of the connector. The greater this flexibility, the more independent are the two halves of the connector. The degree of in- dependence controls the slope of line st in Figure 1 ; if the two halves are com- pletely independent then st will be horizontal, and up to some value of a the straight line pull force, F,, will not vary.

In the present design, adjacent atom faces are 0.028 in. apart and are beveled at a 4" angle (Fig. 3). Thus the bond angle can be varied up to =k8" before the faces of connected atoms touch. The value selected for N allows this 8" variation with less than 25% decrease in the bond strength.

Requirement 8c, to support in the correct spatial configuration the weight of a side chain grouping of atoms with a minimum horizontal angular deflection, is met by having a tight fit between the connector and socket, (see T and T', Fig. 2). Also, the connector is made as rigid as possible by making the neck, N, as large as possible. Here, requirements 8b and 8c are in competition with one another, and the value selected for N is a com- promise.

Thus by a combination of materials, dimensions, and design of the female socket and male connector, we can obtain satisfactory linkages. Actually to fulfill all the needs, a series of five different but interchangeable con- nectors have been designed: (1) the standard connector to which the

Page 6: Precision space-filling atomic models

670 W. L. KOLTUN

Fig. 4. The locking connector.

Fig. 5. The carbon connector.

Fig. 6. The socket for tetrahedral carbon atoms.

previous discussion referred; (2) a connector to shorten the bond distance by 0.05 A. ; (3) a connector to lengthen the bond distance by 0.08 A. ; (4) a locking connector to prevent rotation; and (5) a connector to hinder rotation about bonds between tetrahedral carbon atoms and between sul- fur atoms.

The locking connector has the same dimensions as the standard con- nector but contains a spline along the center portion (Fig. 4). This spline

Page 7: Precision space-filling atomic models

PRECISION SPACE-FILLING ATOMIC MODELS 671

or key fits into a mating keyway on the socket surface S (Fig. 2) and thus prevents rotation. The locking connector is used with atoms which do not rotate freely around certain bonds, such as the ethylenic carbon atoms, and a.mide carbon .and nitrogen atoms. Such atoms, of course, have keyed sockets.

The carbon connector for hindering rotation about C-C bonds is the same as the locking connector except that the splines on each half of the connector are 180" out of phase and have rounded edges (Fig. 5 ) . The sockets of tetrahedral carbon atoms have three keyways with rounded edges, spaced 120" apart (Fig. 6). When the spline is engaged, rotation about the C-C bond is hindered. However, by applying sufficient force the atoms can be rotated from one keyway position until the spline snaps into the next keyway position. Thus it is possible to maintain connected tetrahedral carbon atoms in the correct relative orientation and to simulate the three-fold rotational potential characteristic of C-C bonds. When free rotation is desired, as in C-C1 bonds, a standard connector is used.

ATOMIC UNITS

The atom units are patterned after the Corey-Pauling How- ever, the new units weigh only about one-third as much since they are hol- low rather than solid. As a result they are not only easier to handle than heavier ones but they put less stress on the connectors. All atoms except hydrogen are rigid and are molded of Iniplex; hydrogen is molded of poly- ethylene and is slightly compressible.

Table I lists the types of atoms in the present set, their dimensional spec- ifications, and other pertinent data. Covalent and van der Waals radii and bond angles are intended to be representative of those occurring in most structures; they agree generally with those used in the Corey-Paul- ing Models, but incorporate a number of changes, reflecting more recent data.8

In evaluating the types of atoms and their specifications, it is important to bear in mind the versatility of the connector. The ability to alter and to maintain a bond angle variation of up to 8", to decrease the bond dis- tance by 0.05 A., and to increase the bond distance by 0.08 A., enables a single atom to be used in a variety of structures. Because of this versatility of the connector, a large variety of structures can be achieved with a relatively small number of different atonis.

It is also important to remember that the primary purpose of the C-P-I< Models is for the construction of macromolecules of biological interest such as proteins and nucleic acids. Because of the high cost of molds, only those atoms are provided which are of general biochemical interest and for which there was thought to be sufficient demand. Although atoms to construct specialized molecules, such as cyclobutane, are not provided, there is enough variety to provide for most of the needs of organic chemists. Since female sockets are available as separate units, special atoms of any

Page 8: Precision space-filling atomic models

TA

BL

E I

IX

men

sion

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nd O

ther

Dat

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mic

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or

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. B

ond

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es

Com

men

t and

oth

er d

ata

Hyd

roge

n W

hite

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near

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r hy

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Whi

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bond

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0.57

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0.

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0.69

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110"

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108'

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126"

Sing

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A. a

bout

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. fro

m s

pher

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and

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re 7

a.

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om;

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bo

nd

angl

e 17

'; fo

r de

tails

see

tex

t an

d Fi

gure

7b.

a

-

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With

inde

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es;

inde

ntat

ions

on

radi

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1.15

A. a

bout

cen

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rs s

pace

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tera

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.1 A

. fr

om s

pher

ical

cen

ter

of

atom

; th

ree

slot

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sur

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of

the

atom

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par

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l to

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re fo

r m

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e sl

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Spec

ial

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tom

s.

Page 9: Precision space-filling atomic models

Nitr

ogen

, am

ide

Car

bon,

am

ide

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e

Bla

ck

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bond

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123"

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3"

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115"

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109'

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125"

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126"

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. to

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. to

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in N

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to a

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etw

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nd a

ngle

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etw

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25"

betw

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en a

nd a

mid

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r ge

nera

l pl

anar

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ond;

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twee

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long

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me

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atic

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mid

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and

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car

bon

in

pnri

ne r

ings

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me

as n

itrog

en,

arom

atic

exc

ept

for

colo

r; fo

r si

x-m

em-

bere

d rin

gs s

uch

as b

enze

ne, p

yrid

ine,

and

pyr

imid

ine.

T

o fa

rilit

ate

cons

trnc

tion

of pu

rine

rin

gs.

(con

tinu

ed)

QI 4

W

Page 10: Precision space-filling atomic models

TA

BL

E I

(co

ntin

ued)

Ato

m

Van

der

W

aals

C

oval

ent

Col

or

radi

us,

A.

radi

us, A

. B

ond

angl

es

Com

men

t and

oth

er d

ata

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r, di

gona

l Ph

osph

orus

, te

trah

edra

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uorin

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ine

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min

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dine

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etal

, co

vale

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onic

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trah

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low

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en

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Bro

wn

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let

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er

Silv

er

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low

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1.35

1.

80

1.95

2

.15

1

. 708

1.46

"

1.04

0.

96

0.57

0.

99

1.14

1.

35

1.32

1.32

1.04

104"

10

9"3O

' -

-

90

90 O

109"

30'

e r p: -

P 2 -

For

cova

lent

oct

ahed

ral

bond

s;

can

also

be

used

for

pla

nar

For

ioni

c oc

tahe

dral

bon

ds;

can

also

be

used

for

pla

nar

con-

fig

urat

ions

. T

hese

ato

ms

may

be

cons

truc

ted

usin

g te

trah

edra

l pho

spho

rous

an

d th

e lo

ng l

ink

to y

ield

a t

etra

hedr

al u

nit

with

a c

oval

ent

radi

us o

f 1.

04 A

.

conf

igur

atio

ns.

Z

Rad

ius

of sp

here

for

cons

truc

ting

atom

; al

l bon

d an

gles

equ

al: a =

p =

y =

6 =

90"

.

Page 11: Precision space-filling atomic models

PRECISION SPACE-FILLING ATOMIC MODELS 675

desired geometry can be constructed by cementing these sockets into wooden or plastic units. Thus these special atoms would be compatible with the connector and could be used with the standard atoms.

HYDROGEN BONDING

Because of the prevalence of hydrogen bonding in macromolecules of biological interest, the models provide for the simulation of H . . 0 and H . - . N hydrogen bonds. A rigid arrow barb or shank, which can lock into holes or slots in appropriate oxygen a,nd nitrogen atoms, is molded on to each of two types of hydrogen bond hydrogen atoms (Fig. 7). In

T

+ l a J fb,

Fig. 7. The linear ( a ) and nonlinear ( 6 ) hydrogen-bond hydrogen atoms.

each, the concave face has a radius of 1.35 A. drawn from a center 1.66 A. from the center of the hydrogen atom. Since the concave face radius, 1.35 A, is the same as the van der Waals radius of oxygen, the two atoms mate perfectly when they are locked with the barb nearest the concave surface; in this position, the 0 . .H distance is 1.66 A. The middle and upper barbs serve to lengthen the hydrogen bond by 0.20 and 0.40 A., respectively. A hole in an adapter cap for nitrogen atoms provides for N . - .H distances of 1.76, 1.96, and 2.16 A.

The nonlinear hydrogen-bond hydrogen, Figure 7b, has the axis of the barb inclined at an angle of 17" to the direction of the covalent bond. Since the covalent bond direction may be varied up to fB", the linear and non- linear hydrogen-bond hydrogens together enable one to vary the angle at the hydrogen atom continuously from 0 to 25".

ROLES OF THE NSF AND ASBC

The preceding discussion outlines the basic technical features of the models which the BBCSS ad hoe Atomic Models Committee recommended to the Study Section in 1961; for further details, see U.S. Patent No. 3,170,2469 which the author has assigned to the U.S. Department of Health,

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Education, and Welfare, and the Study Section Report, which was assigned to the NIH.'O This report ended phase one of the program. nfodels had been designed, and the chief remaining problems were to obtain fi- nancial support from a Federal agency and to find a nonprofit organization to monitor the transition from design to production and to manage the production and distribution of the models.

Shortly after receiving the Study Section's report, the NIH indicated it could not underwrite the cost of the molds. Therefore, attention shifted to the NSF as a possible source of Federal funds.

Fortunately the Study Section had kept the NSF informed of develop- ments since the initiation of the program. From the beginning the NSF recognized the need for the models and expressed great interest in the pro- gram." Consequently the NSF agreed to support the program when a suitable nonprofit organization could be found.

This last hurdle was overcome when the American Society of Biological Chemists, ASBC, agreed to assume responsibility. l2 In December 1962, the NSF contracted with the Society for it to nionitor the transition from design to production and to make the models available commercially. Thus, during 1962, responsibility for the program was transferred from the BBC Study Section and the NIH to the ASBC and the NSF.13

During the past two and one-half years, under the direction of theASBC and its Advisory Committee,14 the program has progressed as follows15:

1. This committee reviewed and approved the basic design and basic dimensions which the previous groups had recommended. Hand made prototypes of all parts to be molded were fabricated. For manufacturing purposes, these contained minor variations of the basic design.

On the basis of competitive bids and site visits, the ASBC selected Consolidated Molded Products, Inc., Scranton, Pennsylvania, to manu- facture the models. The committee worked closely with Consolidated to solve a number of technical problems which normally occur in the transi- tion from design to production. Occasional changes in material speci- fications and design details were required during mold fabrication and trial manufacture.

Seventeen research laboratories have completed recently a two month critical field evaluation of samples from production molds of all atomic units and connectors. The ASBC Committee is assessing the results of this field test and will authorize such modifications as they deem desir- able.

2.

3.

CONCLUSIONS It is anticipated that mold changes will be minor and that the models

will be available through the usual commercial channels16 within two to three months. On the average, they should retail for twenty-five to thirty cents per atom.

With regard to the name of the models the ASBC Advisory Committee has recommended to the Council and membership of the Society ''. that

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P l W C I S I O ~ SPACE-FILLING ATOMIC MODELS 677

the atomic models be given the designation: ‘New Corey-Pauling Space- Filling Atomic Models with Koltun Connectors.’ The Council has of- ficially adopted this name for the models. It is recognized that the name is very long, and it is to be expected that in ordinary laboratory usage, some other, shorter names will be applied, such as ‘Corey-Pauling-Koltun Models’ or ‘C-P-K Models’.”l’ In this paper, I have used the shorter name proposed by the ASBC for the sake of convenience only.

The availability of the models will mark the end of a five-year program, one which could not have succeeded without the cooperation and dedica- tion of many institutions, groups, arid individuals. On behalf of all those who have been involved, I hope the models justify the effort.’*

References and Notes 1. Platt, J. R., Science, 131, 1309, 1960. 2. To a considerable extent, the conversations of John T. Edsall, who played a lead-

ing role, Barbara W. Low, Alexander Rich, and David F. Waugh, then Chairman of the BBCSS, led the stitdy Section to nndertake the project. At the time, W. L. Koltun was consultant to the BBCSS and directed its programming activities, one of which was the atomic models project. The Study Section conducted these activities under a special NIH grant, 1tG-7042. This grant supported the costs of the project through 1961, when W. L. Koltun designed the models. During this period, members of the Stndy Section were: A. C. Burton, University of Western Ontario; J. D. Ferry, Uni- versity of Wisconsin; I). E. Goldman, Naval Medical Research Institute; I. Gray, Georgetown University; W. J. Kanzmann, Princeton University; U. Liddel, National Aeronautics and Space Administration ; J. It. Platt, University of Chicago ; F. W. Putnam, University of Indiana; H. K. Schachman, IJniversity of California, Berkeley; C. Tanford, Dnke University; It. C. Warner, New York University; I). F. Wangh, Biassachnsetts Institnte of Technology; I. Fuhr, Execntive Secretary, National In- stitutes of Health; W. L. Koltun, Massachusetts Institute of Technology. Present in- stitutional affiliations are indicated.

3. Members of the BBCSS ad hoc Atomic Models Committee were: Myron L. Bender, Northwestern University; John T. Edsall, Harvard University; Walter L. Koltnn, National Science Foiuidation; Barbara W. Low, Columbia University; Rirhard E. Marsh, California Institute of Technology; Alan S. Michaels, Massachusetts Insti- tute of Tevhnology ; Alexander Rich, Massachiisetts Institute of Technology; and Albert E. Smith, Shell Developmeiit Company. Although not an official member of the Committee, J. L. Oncley, University of bIichigan, made many useful suggestions.

4. The Committee recognized that, for some purposes, “skeletal” type models are preferred. However, sirice adeqnate “skeletal” models could be obtained, and since they are more specialized than the space-filling type, the Committee felt that priority shonld be given the more general space-filling models.

5. Mobay Chemical Company and l\lonsanto Chemical Company sell this com- mercially under the name Texiii 192A.

6. hlr. Victor Hall, technical plastics consultant to the American Society of Bio- logical Chemists, has designed a tool which makes it easy to separate atoms and to remove the connector from the socket.

7. On behalf of all who have been involved in the development of the new models, the author thanks the Corey-Panling group a t the California Institute of Technology. They graciously provided bliieprints and examples of their models, and thus saved considerable time and energy.

8. Table I also reflects some suggestions which the BBCSS Atomic Models Com- mittee sought from: H. C. Brown, Prirdne University; It. B. Corey, L. C. Panling,

It will be available with the models.

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678 W. L. KOLI’UN

and J. D. Roberts, California Institute of Technology; M. J. S. Dewar, University of Chicago; J. Donohue, University of Southern California; L. F. Fieser, W. N. Lipscomb, F. H. Westheimer, and R. B. Woodward, Harvard University; J. S. Fruton, Yale University; D. Harker, Roswell Park Memorial Institute; G. A. Jeffrey, University of Pittsburgh; V. N. Schomaker, Union Carbide Research Institute; D. P. Shoemaker, Massachusetts Institute of Technology; Gilbert Stork, Columbia University; and K. N. Trueblood and S. Winstein, University of California a t Los Angeles.

9. On February 23, 1965, excactly three years from the date of filing, US. Patent No. 3,170,246, Space Filling Atomic Units and Connectors for Molecular Models, was issued to the author.

10. The details of the early development of the program and of the Study Section’s recommendations to the NIH are contained in a report the BBCSS submitted to the NIH in February 1962 entitled “Space-Filling Atomic Units for Macromolecular Models.” The Study Section recommended that:

1. The models should be produced as promptly as possible. 2. In order to keep the price as low as possible, a government agency, either the NIH

or the National Science Foundation, should underwrite the major mold costs, then estimated at between $125,000 and $175,000.

3. A nonprofit organization should administer these funds and should be responsible for construction, production, and distribution of the models.

4 . This organization, with the advice of the Study Section and its committee, should select, on the basis of competitive bids, a manufacturer to produce the models.

5. If consistent with government policy, the nonprofit organization, with the advice of the Study Section and its committee should select, on the basis of competitive bids, a distributor who would sell to all retailers under the same terms. If this were against government policy, then the manufacturer should sell to all legitimate companies under equal terms.

6. Since continuing management of the program would require funds for mold main- tenance and for making molds for additional atoms, the nonprofit organization should receive a small royalty which would enable it to meet its continuing re- sponsibilities.

7. Finally, if extensive delay were anticipated, all particulars including blueprints should be made available to interested persons.

During 1961, the Study Section had explored the feasibility of each phase of the above procedure and obtained from custom molders estimates of about $150,000 for mold costs and about twenty-five cents for the average retail price per atom. It also made informal inquiries of several profit and nonprofit organizations. The BBCSS also made recommendations concerning related items such as the need to field test prototype models before they are mass produced, the naming of the models, and the publication of the specifications in a scientific journal. The publication, namely the present article, was to precede slightly the appearance of the models.

11. Liaison with the NSF maintained through W. V. Consolazio, who was then Pro- gram Director for Molecular Biology. To a large extent, his interest and effort later led to the Foundation to provide the necessary funds.

12. At about the same time the American Chemical Society also agreed to manage the program if the ASBC proved unable to do so.

13. Coincidentally, a t the beginning of 1962, the author changed jobs from Principal Consultant, BBC Study Section, to staff member of the Science Resources Planning Office, NSF. This provided the Foundation with direct knowledge of the program. It also enabled the author to assist in bringing together the ASBC and the NSF and to serve as the Foundation’s technical representative to the ASBC.

14. Members of the ASBC Advisory Committee are: Robert A. Harte, Executive Officer, ASBC; Richard E. Marsh, California Institute of Technology; Frank W. Put-

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PRECISION SPACE-FILLING ATOMIC MODELS 679

nam, University of Indiana; and Philip E. Wilcox, University of Washington. Victor Hall serves as technical plastics consultant to the Society.

15. For further details see Reports to the Members, ASBC, Summer 1964 and Summer 1965.

16. ASBC annonnced the development of the models to laboratory supply houses through a variety of means, including the insertion of a notice in the November 5, 1964, issite of the newsletter of the Scientific Apparatus Makers Association. Thus far, nine companies have expressed interest in retailing the models to the scientific com- munity and Consolidated Molded Products, Inc., is in process of negotiating equivalent agreements with them.

17. Reports to the Members, ASBC, Summer 1965. 18. All rights reserved, including the right to reproduce this article in whole or in

part in any form, without the author’s permission.

Received July 26, 1965 Revised August 13, 1963