Structural Biology at BCBB

The Bioinformatics and Computational Biosciences Branch's (BCBB) structural biology team develops and applies theoretical and computational methods to biological problems at the molecular level. Our work encompasses a broad range of topics relevant to structural biology, from quantum chemical calculations of small molecules to large-scale simulations of macromolecules and their complexes. Specific topics include the physicochemical modeling of proteins and nucleic acids, mechanism-based design of drugs and image probes, the structure, dynamics, and kinetics of proteins, enzyme mechanisms, molecular recognition, protein-ligand association, and multiprotein complexation. We are also interested in the application of mathematical and statistical methods to data analysis and image reconstruction problems and the integration of molecular and machine learning approaches.

We collaborate with NIAID and NIH investigators to elucidate the molecular basis of disease with the aim of translation. Major projects include the development of anti-tuberculosis drugs and other antimicrobial agents, e.g., against drug-resistant bacteria.

Technologies

Publications

H. Zhao, D. Wu, S. A. Hassan, A. Nguyen, J. Chen, G. Piszczek, and P. Schuck. A Conserved Oligomerization Domain in the Disordered Linker of Betacoronavirus Nucleocapsid Proteins. Science Adv. (2023, accepted)

F. G. Frost, M. Morimoto, P. Sharma, L. Ruaud, N. Belnap, D. G. Calame, Y. Uchiyama, N. Matsumoto, M. M. Oud, E. A. Ferreira, V. Narayanan, S. Rangasamy, M. Huentelman, L. T. Emrick, I. Sato-Shirai, S. Kumada, N. I. Wolf, P. J. Steinbach, Y. Huang, Undiagnosed Diseases Network, B. N. Pusey, S. Passemard, J. Levy, S. Drunat, M. Vincent, A. Guet, E. Agolini, A. Novelli, M. C. Digilio, J. A. Rosenfeld, J. L. Murphy, J. R. Lupski, G. Vezina, E. F. Macnamara, D. R. Adams, M. T. Acosta, C. J. Tifft, W. A. Gahl, and M. C. V. Malicdan. Bi-Allelic SNAPC4 Variants Dysregulate Global Alternative Splicing and Lead to Neuroregression and Progressive Spastic Paraparesis. Am. J. Hum. Genet. (2023, in press)

A. Ricciardi, S. A. Hassan, O. Kamenyeva, S. Bennuru, J. Andersen, and T. B. Nutman. A Parasite-encoded Human IL-10 Receptor Antagonist Reveals a Novel Strategy Used to Modulate the Host Response in Filarial Infections. Proc. Natl. Acad. Sci. (USA) Nexus 4, 1 (2022)

S. Batzios, G. Tal, A.T. DiStasio, Y. Peng, C. Charalambous, P. Nicolaides, E.-J. Kamsteeg, S.H. Korman, H. Mandel, P.J. Steinbach, L. Yi, S.R. Fair, M.E. Hester, A. Drousiotou, and S.G. Kaler. Newly Identified Disorder of Copper Metabolism Caused by Variants in CTR1, a High-Affinity Copper Transporter. Hum. Mol. Genet. 31, 4121 (2022)

V. Vishwesh, T. H. Colligan, G. T. Lesica, D. R. Olson, J. Gaiser, C. J. Copeland, T. J. Wheeler, and A. Roy. Drugsniffer: An Open Source Workflow for Virtually Screening Billions of Molecules for Binding Affinity to Protein Targets. Front. Pharmacol. 13, 1 (2022)

H. Zhao, A. Nguyen, D. Wu, Y. Li, S. A. Hassan, J. Chen, H. Shroff, G. Piszczek, and P. Schuck. Plasticity in Structure and Assembly of SARS-CoV-2 Nucleocapsid Protein. Proc. Natl. Acad. Sci. (USA) Nexus 1, 1 (2022)

S. A. Hassan and P. J. Steinbach. Modulation of Free Energy Landscapes as a Strategy for the Design of Antimicrobial Peptides. J. Biol. Phys. 48, 151 (2022)

M. R. Iyer, R. Cinar, C. Wood, C. N. Zawatsky, N. J. Coffey, K. A. Kim, Z. Liu, A. Katz, S. A. Hassan, and Y. S. Lee. Synthesis, Biological Evaluation, and Molecular Modeling Studies of 3,4-Diarylpyrazoline series of Compounds as Potent, Non-Brain Penetrant Antagonists of Cannabinoid-1 Receptor with Reduced Lipophilicity. J. Med. Chem. 65, 2374 (2022)

See a more complete list.

Research Team

Team Lead

Peter J. Steinbach, Ph.D.

Contact: steinbac@exchange.nih.gov

Education:

Ph.D., Physics, 1990, University of Illinois, Urbana-Champaign

Dr. Steinbach came to the NIH in 1990 as a postdoctoral researcher, led the Center for Information Technology's (CIT) Center for Molecular Modeling for 23 years, and joined the NIAID’s Bioinformatics and Computational Biosciences Branch (BCBB) in 2021. He studies protein structure and dynamics with computational methods, including machine learning, homology modeling, and molecular dynamics and...

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Team Members

Phillip Cruz, Ph.D.

(Contractor)

Contact: phil.cruz@nih.gov

Education:

Ph.D., 1983, University of California Irvine, Irvine, CA

B.S., 1977, California State University Fresno, Fresno, CA

As a research scientist at the National Institutes of Health (NIH), Phil performs structural biology computations in collaboration with NIH intramural researchers. Before joining the NIH, he was on the faculty of Wright State University School of Medicine, and then worked in industry at the molecular modeling company Tripos. His research utilizes molecular modeling, simulation, and advanced...

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Sergio A. Hassan, Ph.D.

Contact: hassan@mail.nih.gov

Education:

Ph.D. 1997, University of São Paulo, Campinas, Brazil

Languages Spoken: Spanish, Portuguese

Sergio A. Hassan, Ph.D. uses computers to study the structure, dynamics, kinetics, and thermodynamics of proteins and their complexes. His work integrates research and development. His research interests include: Macromolecular interfaces and molecular recognition Protein-ligand interactions and multiprotein complexation Methods development Current projects include: Modular workflow to integrate...

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Yong-Sok Lee, Ph.D.

Contact: leeys@mail.nih.gov

Education:

Ph.D., 1988, Georgetown University, Washington, D.C.

Languages Spoken: Korean

Dr. Lee collaborates with NIAID and NIH investigators to elucidate the molecular basis of diseases with the aim of drug discovery. In this endeavor, computer simulations are being carried out to investigate the reaction mechanism of small molecules, enzyme mechanisms, and protein-ligand interactions. His major projects include the discovery of new drugs for Mycobacterium tuberculosis and other...

Learn more about Yong-Sok Lee, Ph.D.

headshot of Yong-Sok Lee
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