 .gif)
|
Wei Wang
Inference of gene regulatory networks and determination of protein specificity
|
| Contact Information |
| Office: UH 4254 |
| Phone: (858) 822-4240 |
| Fax: (858) 822-4236 |
| Email: wew002@ucsd.edu |
|
|
| View group members
|
|
| Education and Appointments |
| 2000 |
Ph.D., University of California, San Francisco
|
| 1996 |
M.S., University of Miami
|
| 1993 |
B.A., Tsinghua University
|
| Awards and Academic Honors |
| 2001-2003 |
Postdoctoral Fellow, Stanford University |
| 2000 |
American Chemical Society CCG Excellence Award |
| Research Interests |
The theme of our research is to infer gene regulatory networks and understand the evolutionary principles and molecular mechanisms that determine the behavior of the networks. We are interested in studying fundamental biological problems using computational algorithms that integrate information from gene expression, DNA sequence and protein-protein interaction.
A simplified sketch of such regulatory networks is shown in the figure on the right. Diverse environmental changes are detected, causing signals to be transduced through signaling pathways. Particular transcription factors are then activated and transported into nucleus to transcribe their target genes. Protein products of these genes interact with other proteins in the same or other signaling pathways to further tune responses to extracellular stimuli, thus producing a variety of feedback loops.
Our current research is focused on determining the topology of regulatory networks and building mechanistic models to elucidate underlying mechanisms, which includes the following two directions:
1. Determining protein interaction specificity and signaling pathway hierarchy. Specific protein-protein interactions are critical for signal transduction. We are developing computational methods that combine information obtained from physical chemistry studies such as free energy calculation and bioinformatics studies such as sequence conservation analysis. Our goal is to determine interaction specificity as well as interaction partners of every protein in the genome.
2. Identifying target genes of transcription factors and the cooperation between transcription factors. We have been developing algorithms to (1) construct transcription module that consists of a transcription factor, its binding site and its target genes; (2) identify environmental conditions or genetics perturbations under which a transcription module is activated; (3) infer combinatorial regulation conveyed by several transcription factors.
|
| Primary Research Area: |
Interdisciplinary Specialties: |
|
Biochemistry
|
Biophysics
Computational and Theoretical
|
| Image Gallery: |
|
|
| |
|
| Selected Publications |
-
A systematic approach to reconstructing transcirption networks in Saccharomyces cerevisiae. With J. M. Cherry, D. Botstein and H. Li., Proceeding of the National Academy of Sciences of the United States of America, 99, 16893 (2002).
-
Computational study of protein specificity: the molecular basis of HIV-1 protease drug resistance. With P. A. Kollman. Proceeding of the National Academy of Sciences of the United States of America. 98, 14937 (2001).
-
An analysis of the interactions between the Sem-5 SH3 domain and its ligands using molecular dynamics, free energy calculations and sequence analysis. With W. A. Lim, A. Jakalian, J. Wang, J. Wang, R. Luo, C. Bayly, and P. A. Kollman. Journal of the American Chemical Society. 123, 3986 (2001).
-
Biomolecular simulations: Recent developments in force fields, simulations of enzyme catalysis and protein-ligand, protein-protein and protein-nucleic acid non-covalent interactions. With O. Donnii, C. M. Reyes and P. A. Kollman. Annual Review of Biophysics and Biomolecular Structure. 30, 211 (2001).
-
Use of MM-PBSA in Reproducing the Binding Free Energies to HIV-1 RT of TIBO Derivatives and Predicting the Binding Mode to HIV-1 RT of Efavirenz by Docking and MM-PBSA. With J. Wang, P. Morin and P. A. Kollman. Journal of the American Chemical Society. 123, 5221 (2001).
-
Free energy calculations on the HIV-1 protease dimmer stability using molecular dynamics and a continuum model. With P. A. Kollman. Journal of Molecular Biology. 303, 567 (2000).
-
What determines the van der Waals coefficient beta in the LIE (linear interaction energy) method to estimate binding free energies using molecular dynamics simulations? With J. Wang and P. A. Kollman. Proteins. 34, 395 (1999).
|
|
|
