STEP Experience Reflection 13-14

 

What? – A detailed description of what you did during your STEP experience.

Organophosphorus compounds (OPs) are toxic nerve agents used in chemical warfare. These OPs covalently bond with Serine-203, a main catalytic residue in acetylcholinesterase (AChE), to prevent the hydrolysis of the neurotransmitter acetylcholine. After a given period of time depending on the OP compound, the now inhibited AChE will undergo an irreversible process known as aging, where the OP-AChE moiety will dealkylate and form a stable phosphonate anion permanently inactivating the enzyme. Without functioning AChE, acetylcholine accumulates in the neuromuscular junction and affected individuals can experience muscle spams and eventually death by asphyxiation. Currently, there are no known therapeutic methods to reverse this aging process and regain enzymatic activity. However, inhibited AChE can be restored to the active form before it becomes aged by pharmaceuticals containing an oxime functional group. The goal of this project is to discover a compound that will realkylate the stable phosphonate anion on Ser-203 in aged-AChE, which can then be restored to the active AChE by oximes. Literature precedent shows that quinone methides (QMs) are capable of alkylating phosphodiesters, which are structurally similar to the phosphonylated Ser-203 residue in the aged-AChE active site. Through computational analysis via molecular docking and molecular dynamics, the chemical interactions between the Ser-203 residue and a diverse library of QMPs are being examined in silico. From this critical series of computational experiments, promising compounds can then be identified, synthesized, and tested to discover a lead compound based on observed trends.

 

So What? – A personal response to your STEP experience, including feelings, thoughts, judgments, and what you have learned about yourself and your assumptions from what you did and how you reacted.

Throughout my exposure to the research process, I have learned valuable lessons pertaining to the research project itself and life outside of academia. Research is far more tedious than I imagined—it encompasses meticulousness, patience, frustration, and critical thinking. When a step in the process is halted or slowed, one must be creative to find another way to get the end result. This is where the patience and frustration simultaneously arise. It is frustrating to wait for a job to complete, especially if it is has been done multiple times. Patience is required during this task because it is easy to anticipate the following steps. However, one must follow each step meticulously to ensure successful completion. From learning this, I have become better at multi-tasking and preparing for the next step when possible. Outside of research, I have learned a great deal about the people with whom I have worked; I have learned their strengths and weaknesses, and I know who the right resource is for an appropriate question I may have. Thus, I am a part of the teamwork established within the group.

 

 

Now What? – Discuss how the things you experienced and learned during your STEP experience will affect your academic, personal, and life goals moving forward.

My career goal is to become a physician, and as a current applicant for medical school, I feel my STEP experience in research will give me an advantage over other applicants. First of all, because I am doing computational organic chemistry, I have become proficient in a language that not many people can understand. What is important, though, is that I am still able to convey the seemingly cryptic information into layman’s terms. This will help me in my career because as a physician, medical jargon has to be translated for a patient who probably does not know medical terminology. Beyond the factual evidence, my research has prepared me for my personal goals, too. As stated in the aforementioned paragraph, I have learned about the people I have worked with. As a prospective healthcare professional, communicating with people on a personal basis is a significant matter. Communication has the potential to build trust, to establish strong connections with patients, and to offer compassion and understanding. Thanks to STEP, I am participating in something I never imagined myself doing. When I first started college, I did not even think of participating in research, presenting at forums, or writing a thesis. Now, it seems only natural that I am doing so, and the skills I have learned are skill I will carry with me for my academic and professional career and for life beyond medicine.

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