Eighteenth Annual
_______  .   a 1", _
AM. PM. I .: l: .2 Symposmm on
9:00 Registration and CoffeeRoom 137, 12:15 Buffet Lunch, Faculty Club (Please return ; 1. lil :- t;
Chemistry-Physics Building card by April 9, 1992 for reservations. Cost , > g llf l .
$7.00 to be paid at registration.)  i . 5 71 .
9:30 Welcome by Dr. Lee Magid, Vice President .I . i ,. If; I emls
for Research and Graduate Studies, 1230 Dr. Kenneth Dill, University of California, .I 5' .
University of Kentucky, Room 139, San Francisco I:
Chemistry-Physics Building The Stabilities and Kinetics of Protein
9:40 Introductory RemarksDr. Mark Meier,
University 0 Kentucky We are interested in the forces that determine the relationship
9:45 Dr. Robert L. Baldwin, Stanford University between the amino acid sequence of a protein and its structure M o lecular
Pathways of Protein Folding" and kinetics, Usmg Simple models of short chains on lattices, we
search conformational and sequence spaces to find the relation-
There is general agreement today that structured folding ships between sequences and structures. We assume the domi .
intermediates are populated in favorable conditions on the kinetic nant forces are hydrophobic interactions and conformational lo 0
pathways of folding of small proteins. A principal tool for entropies. We find that some sequences collapse in poor solvents
characterizing their structures is by pulse exchange with solvent to compact conformations with hydrophobic cores, secondary
(1H-2H) of the peptide NH protons in the polypeptide structure, and few native states (often only one). A significant frac
backbone, followed by 2D 1H~NMR analysis after folding is tion of all possible sequences are relatively protein-like in water,
complete. Results of this technique show that native-like secon i.e., compact and with much secondary structure. They fold along
dary structures, both a-helices and -sheets, are formed early in kinetic pathways, the cooperativity being due to conformational
folding. Equilibrium molten globule" intermediates are attractive entropy. Interestingly we find that the problem of protein design .
subjects for study because it is possible to characterize in detail (Le. inverse folding: given a desired native structure, find a good
their structures and the interactions that determine these struc- sequence that folds to it) has much lower computational complexity ,
tures. Molten globule forms of different proteins exhibit a compact than the protein folding problem, which is computationally difficult.
conformation, a high content of apparent secondary structure, . - established in the memory Of
and few if any fixed tertiary interactions, Two classes of molten 2:40 Discusswn
globule forms are observed: structured molten globule in . . Anna S Naff
termediates, with Liz-helices at the same location as in the fully fold 250 D" 5351 van der Vies, DuPont Central
ed forms, and collapsed unfolded forms, which show no signifi- Research and Development . .
cant protection of any amide proton. Molecular Chaperones and their Role in _ "'_ "-
Protein Folding" L0
1045 Discussion > 8 PROTEIN FOLDING
Molecular chaperones are defined as a family of unrelated classes 3:; O
10:50 Dr. Barry Honig, Columbia University of protein that mediate the correct assembly of other polypep .59 ii (5 _-
Hydrophobic and Electrostatic tides, but are not themselves components of the final functional g o 8
Contributions to Protein Stability structures, The concept of molecular chaperones suggests that L E o SPEAKERS
_ _ interactions within and between polypeptides and other molecules U S V
The balance of forces that determine the denaturation free d b It d d h b b'l ff . f A X .
' f lobular roteins will be discussed Our ma'or con- nee to e contro e to re ucet e pro a my 0 ormation O O D R b t L B 1d 
energies 0 g . p _ I _ ' . I) . incorrect structures. This control is exerted by pre-existing proteins H :C 0 er  a Wln
cluSions are: a) Ionizable amino aCids are slightly destabilizmg but . . . . . . . H 0 ~
. I acting as chaperones to inhibit incorrect molecular interactions. C3 , Barry Honlg
make only a marginal contribution to the net free energy balance. . . . . .. Q) D\ C _
. _ _ . It is argued that in the assembly process there is a certain probability E 2:: 0 Kenneth Dill
b) The fact that the enthalpies of unfolding are quite small despite . . . . . a) +4
I l 'd f l b'l' . h l h t that incorrect interactions Will produce nonfunctional structures. 4: i... m S k Cl V ,
experimenta eViLence 01a arge sta 2mg ent .a py suggestst a Where this probability is small, self-assembly needs no assistance, 5 g) E as 1a van er les 
there must be a missing destabilizmg enthalpic contribution. c) . . . . Q. .._. x
h h d h b' ff . 't l d . 't d . t t but where it is high, molecular chaperones are essential to produce Q) c: Q)
t e y, rop 0 1C e ed '5 qu1 e arge an Its magni u e pom I5 0 sufficient correct structures for cellular needs. Q :3 ._.l
the eXistence of a large compensating free energy contribution. .
d) Both b and c can be explained by the cost associated with bury~ 3150 Discussion Monday, April 13, 1992
ing" polar groups (including those that form hydrogen bonds) in Department Of Chemistry
the polar interior. Finally, our breakdown of free energy contribu- 4:00 Mixer. 0 University Of Kentucky
trons has led to the development of a relatively fast algorithm which _
distinguishes stable from unstable protein conformations. LQXIDQTOH, Kentucky 40506-0055
11:50 Discussion