Principal Scientist, Biophysics

Structure Therapeutics develops life‐changing medicines for patients using advanced structure‐based and computational drug discovery technology. The company’s platform combines the latest advancements in visualization of molecular interactions, computational chemistry, and data integration to design orally available, superior small molecule medicines that overcome current limitations of biologic and peptide drugs. We are advancing a clinical‐stage pipeline of differentiated treatments focused on chronic diseases with high unmet need, including cardiovascular, metabolic, and pulmonary conditions.

Structure Therapeutics is led by an experienced group of international drug innovators and financed by top-tier global life sciences investors. The company has completed an initial public offering (IPO) in February of 2023. With offices in California and Shanghai, Structure Therapeutics has the benefit of being at the center of life science innovation in both the US and China and capitalizing on the strengths of each geographic location.

Position Summary

The Molecular Interactions Team at Structure Therapeutics is seeking a biochemist to be responsible for the design, implementation and execution of experiments and assays run at external CROs to characterize the binding of small molecule ligands to G-protein couple receptors (GPCRs). The formats of these assays will include “high throughput” assays for identifying new ligands, but just as importantly, low throughput assays and experiments to confirm and accurately measure the affinity of ligands for receptors, determination of binding kinetics as well as the subsite on the receptor to which the ligand is binding. A deep understanding of the physical biochemistry principles to appropriately select the conditions and settings used to obtain valid binding parameters is essential. The candidate will work closely with the Structure Therapeutics Platform team, as well as member of Discovery teams to understand the needs of each program, and to deliver accurate and reliable results that support progression of the program to higher quality hits and leads.  In addition, this role will support the binding formats used by teams utilizing DNA encoded libraries (DELs) and Affinity Mass Spec (ASMS) selections and follow up studies. 

Essential Duties and responsibilities

• Based on the program needs and the particular properties of the receptor under study, design assays and experiments to understand the binding of small molecule ligands to GPCRs.

• Select the most appropriate assay format (e.g. plasmon resonance, radioactive competition) to achieve the most reliable yet cost-effective assays

• Understand the underlying physical biochemistry of the binding experiments so that appropriate conditions are used. Be able to explain to project team the theoretical basis of the assay

• Support the design and analysis of DEL and ASMS experiments and guide the team in understanding the implication of protein and ligand concentrations in these studies.

• Report findings at research and project meetings in a clear and concise manner.

• Identify and oversee CROs where the bulk of these studies will be performed

• Work with external advisors to validate protocols and revise as needed

• Other duties as assigned

Qualifications

• Ph.D. with 3-8 years of experience or Masters with 7-12 years of experience
  • Preference for candidates with industry experience
• Hands-on experience with one or multiple biophysical and biochemical binding assays, including SPR, aMS, Tm assay and others, is required.
• Experience utilizing the principles of physical biochemistry to design and execute experiments solving problems related to ligand binding to proteins and possibly fragment-based screening
• Experience with Excel as well as curve fitting software and other tools to process quantitative data
• Critical thinking and demonstrated ability to effectively communicate with team members
• Effective oral and written communication skills; the ability to clearly communicate complex concepts to a more general scientific audience
• Skilled in reading, writing, and speaking English