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Computational Biochemistry @ ASDRP

Brah Research Group

 
People | Brah Research Group

Synthesis of Aβ-42 Inhibitors

Aβ-42 is an amyloidogenic protein linked with the progression of Alzheimer's disease. This project, in conjunction with the Biomedical Research Cluster, uses a combined computational-synthesis approach. Molecular dynamics simulations are used to gauge inhibitor binding, while the modeled inhibitors are synthesized using natural product precursors.

Computational-Structural Studies of Etoposide and Etoposide Analogs

Etoposide is currently a widely-used drug in the clinic for the treatment of cancer, and it works by blocking the action of topoisomerase in rapidly-dividing cells. Many have sought to modulate its activity by development of analogs (Meresse et al. Curr. Med. Chem, 2004 11(18), 2443.) Here, we seek to develop and optimize etoposide analogs which have the potential of improved selectivity and therefore lower dosage requirements in cancer treatments.

Ligand Modeling and Docking in Lysozyme

Lysozyme (N-acetylmuramide glycanhydrolase) is an important enzyme that is responsible for hydrolysis of bacterial cell walls, and thus serves an important antimicrobial function in living systems. However, several bacteria evade lysis by lysozyme via the production of small molecule and macromolecule inhibitors. (Deckers et al. Cellular and Molecular Life Sciences 2004 61(10), 1229).Here, we seek to characterize such inhibitors and develop small molecule conjugating agents reduce the binding efficacy of these inhibitors to lysozyme, as a potential therapeutic method for lysozyme-resistant bacteria. 

In Silico Development of Small Molecule Anti-Cancer Compounds Targeting RAS

Overexpression of the Ras oncogene has been linked to the development of several types of cancer, and many have previously described the role of computation in drug discovery (Shima et al.PNAS 2013, 110(20), 8182). Here, we seek to develop small molecule therapeutics through function-informed design backed by computational evidence.  

 
Harman S. Brah
Principal Investigator
ASDRP Department of Chemistry & Biochemistry
harman.brah@fremontstem.com 
Research Students
Coming Soon! The Brah Research Group is recruiting high school researchers in computational biochemistry.
Research | Brah Research Group
 
Tools & Techniques | Brah Research Group

Ligand Docking

The Brah group heavily uses AutoDock / AutoDock Vina (produced by the Scripps Research Institute) to elucidate exact protein-ligand interactions and to quantify binding efficacy. This is used towards function-oriented drug design. 

Mechanistic Enzymology

Through methods developed in classical biochemistry, we are interested in the role of ligands in the functionality of enzyme kinetics. This is resolved spectroscopically.

Function-Informed Drug Design

We use new knowledge elucidated through structural and computational studies to inform optimization and engineering of drugs and small molecule therapeutics with biomedical relevance. 

Structural Biology

We heavily rely upon literature precedent in structural biology to determine the 3-dimensional structural and biophysical characteristics of macromolecular targets. A molecular-level view of this allows us to more fully interrogate ligand interactions. 

High-Throughput Screening

The advances made in in silico methods as well as in vitro methods have made it possible to conduct high-throughput screening of lead molecules that have the potential of therapeutic value in human health.

Molecular Dynamics

The Brah group uses GROMACS  to model force field interactions and time-resolved molecular dynamics simulations towards better understanding bulk solution behavior in macromolecular structure.

Past Work | Brah Research Group
 
  1. Jonnalagadda, K., Kuo, B., Mannemela, V. & Vaidya, T. (2018). Molecular Visualization for Development of a Novel Ligand for Hen Egg-White Lysozyme (HEWL; 1DPX). ASDRP Communications 1(1), 129-136.

  2. Huang, K., Kulkarni, Y., & Lin, C. (2018). Computational modeling of new ligand interactions with the α-amylase enzyme. ASDRP Communications 1(1), 137-141.

Right: The Brah Research Team presents their work at the 2018 Fremont Youth STEM Research Symposium & Expo.