Not so very long ago, the idea that one could calculate even simple molecular structures from mathematical equations was treated with hearty skepticism. Now, however, Teresa Head-Gordon, a physical chemist in the Life Sciences Division, is using such algorithms to solve one of the most complex structural problems in molecular biology--the folding of proteins.
Proteins are large molecules made from the linking together of specific sequences of amino acids. A key to the multitude of chemical tasks performed by proteins is that their chains of amino acids can bend and twist, enabling a protein molecule to fold over and around itself. Understanding the mysteries of protein folding may make it possible for scientists to repair defective proteins that cause disease and other health problems, and to design new and improved synthetic proteins for biotechnical applications.
Such understanding will also enable scientists to more quickly apply the knowledge gained from the Human Genome Project.
"Biologists want to know the structure of a protein just from an amino acid sequence," says Head-Gordon. "However, it is not certain you can make algorithms that predict protein structures from primary sequences without a better understanding of the forces that drive folding."
Head-Gordon is taking a holistic approach to unraveling the mysteries of protein folding. She is first designing specific algorithms that address three basic issues: folding kinetics; folded structure and thermodynamics; and the accuracy of computational predictions. These specific algorithms are expected to provide the basic knowledge needed to develop comprehensive structure-predicting algorithms.
One of Head-Gordon's first successes was an algorithm she calls "antlion," after the insect that digs a hole and waits for its prey to fall in. From a given amino acid sequence, the antlion algorithm can predict highly accurate structures for small proteins like melittin (bee venom), which is composed of about 26 amino acids. Predictions are determined by mathematically "trapping" a protein into its lowest--hence most structurally stable--potential energy state.
Although the antlion method provides a framework for predicting the structures of large proteins, Head-Gordon says it also exposes its own limitations, such as failing to explain what forces cause the protein to fold in the first place.
"There has been much debate over whether the early stages of folding are controlled by environmental influences, such as water, or by the specific sequence of a protein's amino acids," she says.
Her latest algorithm, which models proteins in pure water, may shed new light on the debate. Proteins are formed in an aqueous solution and their hydrophobic (water-repelling) nature is thought to be responsible for a collapse to a compact structure. This collapse is believed to trigger the folding process.
Using her "water" model, Head-Gordon has been able to accurately characterize hydrophobic interactions for methane--a molecule in which a single carbon atom is bonded to four hydrogen atoms. Methane is analogous to a small alanine protein.
"This water model can be used to fully characterize the thermodynamics of protein folding," she says. "Future work with it will involve characterizing hydration for other amino acid sidechains and backbones to ultimately piece together a simple but physically realistic picture of early folding events."
The fact that her work with the water model to date implies that folding starts as a consequence of structural collapse means it is not the amino acid sequence but the environment that drives the process. However, Head-Gordon says further studies with solutions more realistic than pure water are needed.
The key to developing comprehensive predictive models of protein structures, she says, will be the continued development of reliable "neural networks" that associate patterns of amino acids with known protein structures. Out of a suspected 40,000 or more protein structures, only about 400 have been structurally identified.
"We have already achieved a significant improvement in the accuracy of our computational predictions by paying more attention to neural network designs," she says.
Expanding the number of known protein structures and their associated neural networks could help scientists find out how protein folding takes place.
"Predicting the structures of proteins from computational algorithms is certainly possible," she says. "The ultimate test will be to see how our models compare to experimental results."
Established in 1848, the AAAS is the world's largest federation of scientists, with more than 140,000 members. It publishes the authoritative weekly journal, Science.
The new LBL fellows are:
Volunteers should be willing to commit to a thorough reading of the 200-page document and to participate in two meetings before the February 28 deadline. To obtain a copy of the proposed standards, call (203) 334-1399.
1/11, Forklift Truck Safety (EHS 225), 8:30-10 a.m., 90-3132
1/11, Crane/Hoist (Level 1) Training for Incidental Operators (EHS 211), 8 a.m.- noon 62-255
1/11, First Aid (EHS 116), 8 a.m. - noon, 48-109
1/12, Accident Reporting/Investigation (EHS 815), 10 a.m.- noon, 90-2063
1/13, Introduction to Environment, Health & Safety at LBL (EHS 010), 9-11:30 a.m., 66 Aud.
1/13, Fire Extinguisher Use (EHS 530), 10-11:30 a.m., 48-109
1/17, Chemical Hygiene & Safety Training (EHS 348), 9 a.m. - noon,90-2063
1/17, Laser Safety (EHS 280), 1-3:15 p.m., 90-2063
1/18, Adult CPR (EHS 123), 9 a.m. - noon, 48-109
1/18 & 20, Radiation Protection - Radiological Worker I (EHS 430), both days 8 a.m.- noon, 66-316
1/19, Blood Biosafety Training (EHS 735), 9-10:30 a.m., 90-3148
1/20 , Lockout/Tagout (EHS 256), 9 a.m. - noon, 90-4133
1/23, Machine Tool Safeguarding (EHS 245) 10 a.m.- noon, 90-1099
1/24 & 26, Radiation Protection - Radiological Worker I (EHS-430), both days 8 a.m.- noon, 66-316
Pre-registration is required for all courses except Introduction to Environment, Health & Safety at LBL (EHS 10). Call the Emergency Preparedness Office at X6554 to register for: CPR, First Aid, Fire Extinguisher Use, Earthquake Safety, and Building Emergency Team Training. Call X6612 or send a fax with your name, extension and employee number to X6608 to pre-register for all other EH&S courses.
In an interview just before Christmas with the weekly publication Inside Energy, Secretary of Energy Hazel O'Leary insisted she will serve her full four-year appointment and expressed confidence that her department can justify its existence. "I'm not leading us down a path to dismantle the Department of Energy," O'Leary said. "I'm moving down a path that says we are poised now for this self-examination." O'leary also said she will press ahead in her efforts to bring a more business-like climate to DOE through a sweeping realignment. Deputy Energy Secretary William White has been organizing an "employee team" of about 40 persons from throughout DOE to craft a new organization plan. O'Leary would like to complete this reorganization within six months.
O'Leary said she will consider options for cutting redundancies in DOE and enhancing operations, which means that DOE headquarters and field offices will come under close scrutiny. "We have a presence in 35 different states and not only confusion but sometimes redundancy in terms of functions," the Secretary said. "This redundancy has to be stripped out." She acknowledged that the Department of Energy might not be the proper name for a department whose responsibilities include not only energy policy, but also nuclear weapons, environmental cleanup, and science and technology. As to reports of Congressional or White House discussions about possibly abolishing the department, the Secretary maintained that no one is likely to propose eliminating any of DOE's major functions. "Science and technology are the heart and soul of the place," she said, primarily reflected in the national laboratories. DOE's role as custodian of nuclear materials and its responsibility for cleaning up the pollution left behind by 40 years of nuclear weapons production would have to be done by someone. "Now if you ask the question, can these functions be performed in a more cost-effective way, my answer is yes, and that is what we have been struggling with for the almost 23 months we've been at this job," O'Leary said.
LBL PEOPLE:
Eugene Veklerov of the Engineering Division has been named associate editor of the International Journal of Imaging Systems and Technology.
Monday, January 9
OPEN CALENDAR
T u e s d a y, January 10
UPTE-LBL LOCAL 184 GENERAL MEETING
11:30 a.m.-1:30 p.m., Bldg 90-4133: to bring nominations and discuss issues prior to 1/18 meeting when delegates will be elected to the 1/22 Northern California Bargaining Conference.
FAREWELL OPEN HOUSE
There will be a farewell open house for Kathleen Handron on Tuesday, Jan. 10, from 2 to 4:30 p.m. in Bldg. 26 (Medical Services). Handron, coordinator of LBL's Employee Assistance Program, is leaving the Laboratory after 14 years of service. All employees are invited to attend.
LIFE SCIENCES DIVISION SEMINAR
"Tamoxifen Activation of the Estrogen Receptor/AP-1 Pathway: Potential Origin for the Cell-Specific Estrogen-like Effects of Antiestrogens," P. Kushner, Metabolic Research Unit, UCSF,
4 p.m., Bldg 66-316
PHYSICS DIVISION RESEARCH PROGRESS MEETING
"Observations of [[pi]]-B Charge-Flavor Correlations and Resonant B[[pi]] and BK Production," R. Kowalewski, CERN , 4 p.m., Bldg 50A-5132, refreshments, 3:40 p.m.
W e d n e s d a y, January 11
EH&S CLASSES
Crane/Hoist (Level 1) Training for Incidental Operators (EHS Class 211), 8:00-10:00 a.m., Bldg 62-255, pre-registration required (X6612).
First Aid (EHS Class 116), 8:00 a.m.-noon, Bldg 48-109, pre-registration required (X6554).
Forklift Truck Safety (EHS Class 225), 8:30-10 a.m., Bldg 90-3132, pre-registration required (X6612).
UPTE-LBL LOCAL 184 GENERAL MEETING
11 p.m.-midnight, Bldg 80 Hi-Bay: to bring nominations and discuss issues prior to 1/18 meeting when delegates will be elected to the 1/22 Northern California Bargaining Conference.
T h u r s d a y, January 12
BLOOD DRIVE
The next LBL blood drive is scheduled for 7:30 a.m. to 1:30 p.m. on Thursday, Jan.12, in the Bldg. 70A main conference room. All employees are encouraged to contribute.
EH&S CLASSES
Accident Reporting/Investigation (EHS Class 815), 10 a.m.-noon, Bldg 90-2063, pre-registration required (X6612).
UPTE-LBL LOCAL 184 GENERAL MEETING
11:30 a.m.-1:30 p.m., location to be announced: to bring nominations and discuss issues prior to 1/18 meeting when delegates will be elected to the 1/22 Northern California Bargaining Conference.
SURFACE/CATALYSIS SCIENCE SEMINAR
"Metal-Support Interface and Electronic Structure of Supported Platinum Catalysts," D. Koningsberger, University of Utrecht, The Netherlands, 1:30 p.m., Bldg 66-317 (Auditorium)
"What Can Be Learned from B > Ds+ X Decays?" S. Menary, UC Santa Barbara, 4 p.m., Bldg 50A-5132, refreshments, 3:40 p.m. (Physics Division Research Progress Meeting).
Fr i d a y, January 13
EH&S CLASSES
Introduction to Environment, Health & Safety at LBL (EHS Class 010), 9:00-11:30 a.m., Bldg 66 Auditorium.
Fire Extinguisher Use (EHS Class 530), 10:00-11:30 a.m., Bldg 48-109, pre-registration required (X6554).
CENTER FOR BEAM PHYSICS SEMINAR
"Femtosecond Spectroscopy of Semiconductors," S. Bolton, UC Berkeley and LBL, 10:30 a.m., Bldg 71 Conf. Rm.
M o n d a y, January 16
MARTIN LUTHER KING, JR. HOLIDAY
T u e s d a y, January 17
EH&S CLASSES
Chemical Hygiene & Safety Training (EHS Class 348), 9 a.m.-noon, Bldg 90-2063, pre-registration required (X6612).
Laser Safety (EHS Class 280), 1:00-3:15 p.m., Bldg 90-2063, pre-registration required (X6612).
W e d n e s d a y, January 18
EH&S CLASSES
Adult Cardiopulmonary Resuscitation (CPR) (EHS Class 123), 9 a.m.-noon, Bldg 48-109, pre-registration required (X6554).
Radiation Protection-Radiological Worker I (EHS Class 430), 8 a.m.-noon, Bldg 66-316 (also 1/20: both days), pre-registration required (X6612).
UPTE-LBL LOCAL 184 GENERAL MEETING
11:30-1:30, Bldg 50 Auditorium: to elect delegates to the 1/22 Northern California Bargaining Conference.
T h u r s d a y, January 19
EH&S CLASSES
Blood Biosafety Training (EHS Class 735), 9:00-10:30 a.m., Bldg 90-3148, pre-registration required (X6612).
SURFACE/CATALYSIS SCIENCE SEMINAR
"Surface Chemistry of Ice: Toward an Understanding of Adsorption at a Molecular Solid," J.T. Roberts, University of Minnesota at Minneapolis, 1:30 p.m., Bldg 66-317 (Auditorium).
F r i d a y, January 20
EH&S CLASSES
Radiation Protection-Radiological Worker I (EHS Class 430), 8 a.m.-noon, Bldg 66-316 (also 1/18: both days), pre-registration required (X6612).
Lockout/Tagout (EHS Class 256), 9 a.m.-noon, Bldg 90-4133, pre-registration required (X6612).
To set up your computer to access the World Wide Web, call the Mac and PC Support Group at X6858.
Sadie's Early Bird: Banana pancakes $1.95
Soup of the Day: Jambalaya reg. $1.35 lg. $1.95
Bistro Fare: Rosemary chicken w/scalloped potatoes & green beans $3.75
Passports: South of the Border a la carte
Sadie's Grill: Bacon cheeseburger & onion rings $3.05
tuesday
Sadie's Early Bird: Corned beef hash & eggs/coffee $2.50
Soup of the Day: Vegetarian split pea reg. $1.35 lg. $1.95
Bistro Fare: Carved roast beef w/potatoes, gravy & peas $3.75
Passports: South of the Border
Sadie's Grill: Tuna melt & fries $3.05
wednesday
Sadie's Early Bird: Biscuit & gravy w/eggs $2.50
Soup of the Day: Hearty vegetable beef reg. $1.35 lg. $1.95
Bistro Fare: New Feature!! Pasta Piatti $3.75
Passports: South of the Border a la carte
Sadie's Grill: Sloppy Joe & potato salad $3.05
thursday
Sadie's Early Bird: Big blueberry pancakes $1.95
Soup of the Day: Manhattan clam chowder reg. $1.35 lg. $1.95
Bistro Fare: Butter chicken over basmati rice w/sweet & sour garbanzos $3.75
Sadie's Grill: Philly cheese steak sandwich & fries $3.75
friday
Sadie's Early Bird: Ham scramble $2.50
Soup of the Day: Minestrone reg. $1.35 lg. $1.95
Bistro Fare: Grilled salmon fillet w/rice & fresh vegetable $3.75
Sadie's Grill: Ham & swiss on rye with fries $3.05
AUTOS/SUPPLIES
SCOOTER, Yamaha Razz, runs well, reliable, $250. Detlef, X4350, 654-9514
'85 HONDA Accord LX, 4-dr,
5-spd., a/c, gd tires, new carpets, reliable, gd commuter car, $3500/b.o. 625-4415
'88 CHEVROLET Camaro RS, 50K mi., fuel injection, p/b,
p/s, 5-spd, a/t, very gd cond., $5500/b.o. 935-9161 (msg.)
'88 CORVETTE, black on black coupe w/2 tops, a/t, Z52 pkg., exc. cond., 33K mi., $17600/b.o. Mark, X7451, 895-0151
'88 HONDA Civic LX, 4-dr, a/t, a/c, am/fm cass., p/s, p/l, p/w, alarm, 65K mi., runs exc., $5000/b.o. Leon X5305, 261-8774
'91 NISSAN 240SX, white, 2-dr, p/s, p/b, a/c, am/fm cass., new tires & rims, mask, $9800. Al Harcourt, X7660
WANTED
HOST VOLUNTEERS for int'l students living on campus, to maintain informal contact & hospitality throughout the yr & during school breaks and holidays. John Ruzek, X5987, 939-5181 (eve.)
MACINTOSH COMPUTERS, printers or monitors, for non-profit literary assoc., tax doc. provided. John, X4897, 339-8950
SIMMS, 1-mg, for IBM type machine, 30 pins x 9; also, old CD-ROM w/card. 482-3030, 2-8745
FOUND
BRACELET, on roadway from Blackberry Canyon parking lot. Carol, X6651
WRISTWATCH, nr bldg 26
12/16. David, X7457
MISCELLANEOUS
BRONZEWARE, setting for 12, from Bangkok, Thailand, circa 1967, only used twice, elegant, unique, 144 pieces, 12 11-pc. place settings & 12 serving pieces, wooden case, $3,250/b.o. Auben, X4613, 245-0343
COUCH $25/b.o., sofabed $50. Sajid Hakim, X5184, 548-0641, shhakim@lbl.gov
ELEC. RANGE, 1986 Corning glass top, model R30JB, 4-burner w/standard oven, clock, mustard yellow color, equiv. to GE JBP-75. $75.00/b.o. Greg Stover, X7706
FUTON & FRAME, queen, $230; queen bed w/frame, $180; TV, 19", $150; stereo $180; dining table w/4 chairs $50; lots more. Ferdinand, X5994, 204-9184
FUTON & FRAME, queen, gd cond., $70. Detlef, X4350, 654-9514
FUTON, w/oak frame, sofabed, great cond., $100. Krista, X7523, 548-3769
GLASS TANK, 35-gal., w/ glass hood, fluor. light, underwater visitherm heater, blue & white gravel & colorful bkgrd, $70/b.o. Joe, 522-4905 eves
MOTORCYCLE JACKET, Motorsport, leather, safari-style, size 40, padded, rem. liner, like new, $195; leather overpants, vent-teck, size 34, padded, rem. liner, $195. John Thompson, 524-1844
PIANO, 1914 upright, ivory keys, bench, antique tiger oak, looks/sounds great, $1850. Peter/Anne, 531-7837
SCANNER, Radio Shack Pro-34 UHF/VHF Programmable w/charger $100; Panasonic Cell. Phone, many features, orig. $450, now $200; Canon E65 Camcorder w/2 batts, charger, car charger, $500. Fred Ottens, X6068, 526-3259
SKI BOOTS, Salomon size 320, approx. size 8, exc. cond., gd for teen or intermed. skier, used only two seasons. $45.
H. Matis, X5031, 339-0584
SKI BOOTS, Raichle, size 7-1/2, $25. Ron, X4410, 276-8079
SKI RACKS, locking, 2 pr, Barrecrafters, adj. width, for snowbds or several pr skis, requires car w/rain gutters, $30/pr/b.o. 642-2156, 527-2937
TV, 24" color Mitsubishi, oak cab., $125. Al Harcourt, X7660
TOTE BAG, navy vinyl Gucci, $50; Precor 714 stair stepper $150; Val St. Lambert crystal pitcher $150; Erte silk scarf "dream voyage" $75; Nintendo gameboy w/4 games $60. Lisa, X6268, 841-4855
TOYS, Playmobile, Duplo bldg. blocks, exc. cond., no parts missing, price negot. Paul Molinari, 235-6602
HOUSING
ALBANY, furn. 1-bdrm apt., wash./dry., nr UC Village & bus to LBL/UCB, quiet family dist., no more than 3 persons, visiting professor w/spouse pref., nonsmokers, $675/mo. Donald Mangold, X6459
ALBANY, 2+bdrm house, furn., lg. study, garage, deck, modern kitch., avail. Jan for 1 yr. $1300/mo. incl. gardener. 526-3349
BERKELEY, cute studio w/skylight, small garden, walk to UC/LBL shuttle/Gourmet Ghetto, $515/mo. 548-9869
BERKELEY, newly remodeled
2-bdrm uppper flat, new hdwd flrs, high ceilings, new appliances, yard, pkg, Ocean View area, $875/mo. 540-0385, 548-9869
BERKELEY, small furn. rm in furn. rooming house, 5-min. walk to UC/LBL shuttle, $435/mo. incl. utils. 540-0385
BERKELEY, furn. 1-bdrm apt, bay view, priv. redwd deck, hardwd flrs, new tile bth, kitch. w/microwave & refrig. only, non-smoker, nr. Claremont Hotel, walk to campus, $750 incl. utils. 849-4588
BERKELEY HILLS, furn. rm in priv. home; on Euclid/Cedar Ave.; 5 blks from campus; kitch. privileges; washer/dryer; deck; view of SF/ Golden Gate/bay; nr. transp./shops/tennis/Rose Garden; no smoking or pets; pref. visitng scholar or FT working person, $450+util. Laura, 548-1287
CONCORD,3-bdrm house,1 new bath, back fence w/gate on park, hdwd flrs, tile entry, new paint, nr BART/shopping/schools, $895 +dep. 689-7213
EL CERRITO, 1 person, furn.,
1-bdrm apt, lvng rm, bth, kitch. only microwave, refrig., cleaning service, lg. garden, bay view, no smoking, nr. bus/BART, rent negot. Alice, 524-1641
KENSINGTON, furn. 3-bdrm house, view, garden patio, quiet, 2 cats, pref. visiting LBL staff, avail. 1/1, rental period flex., $1200/mo. 526-6730
KENSINGTON, furn. studio, pvt, small patio, ideal for one person, short term OK, avail. 1/21, $475 incl. util., cable. 559-8021
NORTH BERKELEY, furn.,
1-bdrm apt (incl. 486 computer), 2/11-4/7, 2 blks from N. Berk. BART, $525/mo+dep. X4093, 849-1929
SAN FRANCISCO Marina share, 1-bdrm in 3-bdrm flat, lvrm w/ fireplace, full kitch., storage area, bkyd, great loc., avail. 2/1, $510/mo+1/3 util. Karen, X7330, 415/771-5157
WANTED: 1-bdrm apt/studio for visiting German scholar at Berk., non-smoker, male, for 14 mo. from 2/1. kober@ruf.uni-freiburg.de or fax/phone c/o Peter, 415/322-9674
WANTED: Studio apt or rm in house, Walnut Creek/Berk./Oak., $325/mo. Catherine, X7249, 947-0447
WANTED: Share in Berk. for UC professor who spends 3-4 days a wk in Berk. priv. rm w/bath in No. Berkeley pref. (916) 758-5015
WANTED: Furn. studio, rm, or houseshare for visiting grad. student researcher 1/14-5/20, pref. Rockridge, Elmwood or N. Berk. Nancy Sallee, X4497
WANTED: 1-bdrm furn. apt nr LBL for visiting researcher 1/26-9/8. Ian, X4174, 548-7102
VACATION
BAHAMAS, 1-bdrm beach condo., sleeps 4, all amenities, Taino Beach Resort Club, $500/wk (Sat.-Sat.), need 2 mos. adv. notice. 528-1614
MENDOCINO COAST, 8 acres, secluded 3-bdrm, 2-bth house, river/ocean view 3 mi. west, 700-ft. elev. grassland, mature forest, grdns, avail. May, $900. Photos. 707/937-4015
SO. LAKE TAHOE 4-bdrm cabin, exc. loc., 2 mi. from Heavenly Valley, AEK, washer/dryer. Bill Holley, X4822, 283-3094
NORTH TAHOE, new 3-bdrm, 2.5-bth house; avail. for wknd or wkdy ski season rental; quiet; greenbelt views; w/in 10 min. of North Star/casinos/shopping/lake/dining; x-country/resort skiing all around; reas. price. Wayne Nordby, X7685, 837-2409
REAL ESTATE
RICHMOND, 2-bdrm split-level MacGregor home, gd neighborhood, 20 min. from LBL, lg. kitch., stove, refrig., washer/dryer, hdwd flrs, new carpet, fam. rm, compact priv. fenced yd w/patio, fruit trees, rock garden, $127,500. Jim, X7231, or Heidi Long, 486-1495
EDITOR:
Mary Bodvarsson, X4014
mgbodvarsson@lbl.gov
STAFF WRITERS:
Jeffery Kahn, X4019
Diane LaMacchia, X4015
Mike Wooldridge, X6249
Lynn Yarris, X5375
EDITORIAL ASSISTANT:
Brennan Kreller, X6566
PRODUCTION:
Alice Ramirez
FLEA MARKET/CALENDAR:
Mary Padilla, X5771
currents_calendar@lbl.gov
fleamarket@lbl.gov
Public Information Department
LBL, MS 65 (Bldg. 65B)
One Cyclotron Rd.
Berkeley, CA 94720
Tel: (510) 486-5771
Fax: (510) 486-6641