32 research outputs found
Potentials of Mean Force for Protein Structure Prediction Vindicated, Formalized and Generalized
Understanding protein structure is of crucial importance in science, medicine
and biotechnology. For about two decades, knowledge based potentials based on
pairwise distances -- so-called "potentials of mean force" (PMFs) -- have been
center stage in the prediction and design of protein structure and the
simulation of protein folding. However, the validity, scope and limitations of
these potentials are still vigorously debated and disputed, and the optimal
choice of the reference state -- a necessary component of these potentials --
is an unsolved problem. PMFs are loosely justified by analogy to the reversible
work theorem in statistical physics, or by a statistical argument based on a
likelihood function. Both justifications are insightful but leave many
questions unanswered. Here, we show for the first time that PMFs can be seen as
approximations to quantities that do have a rigorous probabilistic
justification: they naturally arise when probability distributions over
different features of proteins need to be combined. We call these quantities
reference ratio distributions deriving from the application of the reference
ratio method. This new view is not only of theoretical relevance, but leads to
many insights that are of direct practical use: the reference state is uniquely
defined and does not require external physical insights; the approach can be
generalized beyond pairwise distances to arbitrary features of protein
structure; and it becomes clear for which purposes the use of these quantities
is justified. We illustrate these insights with two applications, involving the
radius of gyration and hydrogen bonding. In the latter case, we also show how
the reference ratio method can be iteratively applied to sculpt an energy
funnel. Our results considerably increase the understanding and scope of energy
functions derived from known biomolecular structures
The Formation of Three-Dimensional Structures of Proteins
(This information was taken from the Distinguished Scientist Lecture Series Program 1983-1984).
Dr. Anfinsen, a Nobel laureate, is Professor of Biology at Johns Hopkins University. Born in Monessen, Pennsylvania, Dr. Anfinsen received the Ph.D. degree in 1943 from Harvard University Medical School. In 1972 he shared the Nobel Prize in Chemistry with Stanford Moore and William H. Stein for their studies of the enzyme ribonuclease. . Dr. Anfinsen was Visiting Professor of Biochemistry at the Weizmann Institute of Science in Rehovet, Israel from 1981 to 1982. He served as Chief of the Laboratory of Chemical Biology of the Nationall Institute of Arthritis, Metabolism and Digestive Diseases from 1963 to 1981. He has taught at Harvard Medical School, served as Chief of the Laboratory of Cellular Physiology and Metabolism of the National Heart Institute and was Visiting Fellow at All Souls College, Oxford in 1970. He has been a Naff lecturer at the University of Kentucky, Kempner lecturer at the University of Texas Medical Branch-Galveston, Mathers lecturer at Indiana University-Bloomington, Jubilee lecturer of the British Biochemical Society, Leon lecturer at the University of Pennsylvania, and Kelly lecturer at Purdue University. He received the 1954 Rockefeller Foundation Public Service Award, a Guggenheim Fellowship in 1958, and a National Science Foundation Travel Award in 1959. Dr. Anfinsen is a member of the American Society of Biological Chemists, the National Academy of Sciences, the Royal Danish Academy, the American Philosophical Society, and the Pontifical Academy of Science.
His Work: Dr. Anfinsen\u27s research interests have included the study of non-uniform labelling in newly-synthesized proteins, study of the relationship between structure and function in enzymes, investigations of an extracellular nuclease of Stnplrylococrns nureus, and study of the isolation and chemical characterization of human interferon. Most recently he has been involved with the study of certain extreme thermophilic bacteria found in vents along the tectonic plates in the Pacific Ocean floor.
His Lecture: March 13, 1984: The Formation of Three-Dimensional Structures of Proteinshttps://digitalcommons.bard.edu/dsls_1983_1984/1000/thumbnail.jp