Contact
info: Lawrence Berkeley National Laboratory
Physical Biosciences Division
One Cyclotron Road
Mail Stop: 3-220 Calvin Lab
Berkeley, California 94720-1460
USA
Research Emphases
Structural Biology
The language used by molecules in cells to communicate with each other
is diverse. Molecular communication is achieved, in many cases, by the
conformational complementarities between communicating molecules along
the chains of signaling pathways. To understand the molecular communication
we study the structures of proteins involved in the signal transduction
pathways associated with cell growth, cell cycle, sensory perception and
chemotaxis. We are also interested in discovering and designing drugs
that inhibit these proteins for therapeutic purposes.
Structural Genomics/Proteomics
An analysis of the genomic sequences of many organisms indicates that
a large fraction of the encoded proteins cannot be assigned a particular
molecular and/or cellular function based on the gene or protein sequence
alone. The molecular (biochemical and biophysical) function of a protein
is tightly coupled to its three-dimensional structure, and the three-dimensional
structure, in combination with sequence information, may provide important
insight into its molecular function. Thus, the structural study of the
proteins encoded by an entire genome or a cellular process—an approach
often called “Structural Genomics” or “Structural Proteomics”—can
provide an important foundation for the understanding of the biological
processes in the whole organism. As one of the NIH supported centers of
the Protein Structure Initiative, Berkeley Structural Genomics Center
is involved in an effort to determine a near complete structural complement
of the proteomes of “minimal organisms,” Mycoplasma pneumoniae
and Mycoplasma genitalium, which have fewer than 500 and 700 genes, respectively.
Two of the objectives are to discover the “basis set” of the
protein architecture that is required to sustain Life, and to understand
how protein structures may have evolved from having simple to complex
architecture to accomplish various tasks essential for a living cell.
Computational Genomics/Proteomics
As a computational counterpart of the Structural Genomics described above,
five aspects of computational biology are being pursued: (1) Knowledge-based
protein fold prediction, where we apply rapid text searching algorithms,
developed by computer scientists, to protein structures to discover similarities
and differences between two protein structures, (2) Global mapping of
conformations of all proteins and nucleic acids to understand the conformational
“landscapes” of these two classes of molecules, (3) “Global
mapping of the protein universe” to classify all proteins into protein
fold families and to discover their evolutionary relationship among the
families, (4) “Remote homologue” detection to discover how
a pair of proteins with no sequence similarities can have the same or
very similar structures and the same or related molecular functions. We
are developing computational methods to predict such remote homologues
by combining several powerful computational algorithms for text searching
on protein structural features: treating the protein structure (a “text”)
as a collection of local structural features (“words”). If
successful, this method will dramatically change the way functional annotation
is done for all genes and proteins, and (5) Functional mapping of protein
structure universe to map the molecular function of the proteins on to
the protein universe map to generate a “dictionary” of protein
structure vs. function.
