Faculty Biography

Shuanghong Huo

Shuanghong Huo, Ph.D.

Computational Chemistry, Biophysics

Professor of Chemistry, Carl J. and Anna Carlson Endowed Chair
Biochemistry and Molecular Biology Program
Clark University
Worcester, MA 01610-1477

Office: S235, Sackler Sciences Center
Phone: 508-793-7533
Email: shuo@clarku.edu

Curriculum Vitae
Research Lab Website

Graduate student position available


Education

Postdoctoral Fellow, University of California, San Francisco, 1999-2001
Ph.D. Boston University, 1999
B.S. Peking University, 1990

Current Research Interests

My research is in the field of computational biophysics. My group studies protein folding/misfolding and aggregation, protein conformational changes that are related to signal transduction, and protein-ligand interactions using computational approaches. My research has been supported by NIH R15 and R01 as well as private agents.

 1. Protein misfolding and type 2 diabetes. Human islet amyloid polypeptides (hIAPP) aggregate into amyloid deposits in the pancreatic islets of Langerhans, contributing to the loss of β-cells of patients with type 2 diabetes. Despite extensive studies of membrane disruption associated with hIAPP aggregates, the molecular details regarding the complex interplay between hIAPP aggregates and raft-containing membranes are still very limited. Using all-atom molecular dynamics simulations, we investigate the impact of hIAPP aggregate insertion on lipid segregation. Our investigations on the interaction between hIAPP aggregates and raft-containing membranes could lead to a better understanding of the mechanisms of amyloid cytotoxicity. We also collaborate with the Jakobsche group in our department to study the properties of the third-generation amyloid-binding bifunctional molecules that can bind to amyloid fibrils and modify the properties of those fibrils by delivering various functional molecular cargos to them.

2. RING-type E3 ubiquitin ligase.  Ubiquitin serves as a tag to selectively label proteins for degradation. E1, E2, and E3 ligases are enzymes acting sequentially in the protein degradation cascade to transfer ubiquitin to the target protein to be degraded. A deep understanding of protein degradation mechanisms will help to design drugs to selectively degrade disease-causing proteins, ranging from those associated with Alzheimer’s disease to cancers. c-Cbl is one of the RING-type E3 ligases. X-ray structures show that in the absence of E2 ligase, c-Cbl adopts a closed conformation before it binds with its substrate. This closed-form is considered to be unactivated in the degradation cascade. While after the substrate binding, the RING domain is partially open, which is the first step of activation of c-Cbl. As a first step to elucidate the details of the activation mechanism, computer simulations have been used to investigate the dynamic features of the closed state of c-Cbl and its partially opened state. Our simulations will provide new insights into the critical role of protein conformational changes in the initial steps of c-Cbl activation.

3. Algorithm Development. In a long-term collaboration with the Han group in the Mathematics and Computer Science department at Clark, we develop computational methods to extract kinetic information from a large number of protein conformations obtained from molecular dynamics simulations. The methods developed in my group include the MaxFlux reaction-path algorithm combined with the probabilistic roadmap motion planning method, graph representation of protein free-energy landscape and diffusion maps with a hybrid geometry energy-based kernel.

Selected Publications

 Tan, Q., Liu, H., Duan, M., and Huo, S. (2021) “Interplay between human islet amyloid polypeptide aggregates and micro-heterogeneous membranes” BBA - Biomembranes 1863, 183691.

 Tan, Q., Duan, M., Li, M., Han, Li., and Huo, S. (2019) “Approximating dynamic proximity with a hybrid geometry energy-based kernel for diffusion maps” J. Chem. Phys. 151, 105101.

 Liu, H., Li, M., Fan, J., and Huo, S. (2016) “Inherent Structure Versus Geometric Metric
for State Space Discretization” J. Compt. Chem. 37, 1251–1258.

 Reardon, M. B., Xu, M., Tan, Q., Baumgartel, P. G., Augur, D. J., Huo, S., Jakobsche, C. E. (2016) “Long-Range Reactivity Modulations in Geranyl Chloride Derivatives” J. Org. Chem. 81, 10964-10974.

 Duan, M., Liu, H., Li, M., and Huo, S. (2015) “Network representation of conformational transitions between hidden intermediates of Rd-apocytochrome b562” J. Chem. Phys. 143, 135101. 

  Li, M., Duan, M., Fan, J., Han, L., and Huo, S. (2013) “Graph representation of protein free energy landscape” J. Chem. Phys. 139: 185101.

 Duan, M., Fan, J., and Huo, S. (2012) “Conformations of islet amyloid polypeptide monomers in a membrane environment: Implications for fibril formation” PLoS ONE 7(11): e47150.