Updates: Combining Docking and Free Energy-Based Methods to Improve Virtual Screening of Drug Candidates Against HIV Integrase

Research done by Dr. Nanjie Deng, myself, and our team this summer has made steady progress. As described in my previous blog post, our research revolves around the use of docking, molecular dynamics simulation, and free energy calculation to improve computational screening of potential HIV-AIDS drug candidates. So far, Dr. Deng has placed emphasis on preliminary research and the usage of Desmond, a software package from D.E. Shaw Research designed to perform molecular dynamics for biological molecules such as those of interest within our research.

In order to accurately predict interactions between drug candidate compounds and HIV integrase (a key protein in the HIV-AIDS virus) within the human body, we first must simulate how a protein exists in solution. Chemical reactions within the human body exist in solution, thus we used Desmond to simulate a “box” of water molecules around the protein we wanted to observe. Doing so using Command Line Interface (CLI) on a computer with Linux, we observed the strengths of hydrogen bonds and other interactions between various atoms (oxygen, nitrogen, carbon, hydrogen, etc.). As research advances, we will be using other 3D shapes of water to surround the protein; this will minimize the number of water molecules required within calculations and, consequently, increase efficiency. According to Dr. Deng, we will be reporting official data soon as our research continues throughout the academic school year and even into next summer. Our data reports shall be sent to a close colleague of Dr. Deng for further testing in a lab setting.

There have been many challenges during our research. Desmond proved to have some issues within its software, seeing that certain simulations failed to proceed, or “died,” and no mistakes on our part were found. This may be due to the fact that Desmond is a free software, and this is why Dr. Deng had already planned to only use Desmond for these beginning stages. Hence, more demanding and specific research shall be executed with more advanced, professional, and reliable molecular dynamics software. However, similar issues can exist in any software, so we must learn to use problem-solving skills to fix any future problems we may encounter. Another challenge I, personally, have encountered is that of learning CLI within Linux. I am a biochemistry major who has had very limited experience in coding. I will need to spend a significant amount of time learning this, but I am grateful; this is a very valuable skill that is utilized in many fields of study. Despite these challenges, I am happy to say that our team has made good progress under the tutelage of Dr. Deng.

Research so far has greatly broadened my horizons and reinforced my dreams of studying medicine and serving the community as a physician. I have always had success and been interested in biochemistry and medicine, but now I have been given the opportunity to learn about the application of coding and computing within the medical field. Not only will learning coding be an enriching experience and a vital addition to my education, but it will also prepare me for medical school and my future career. Working together as a team to achieve new goals has given me insight on how future work in the medical field will be. This work is incredibly important as it serves to help modern medicine find a cure for one of the world’s most merciless diseases, and I am motivated to contribute my knowledge and efforts towards making a change. I did not expect to have such a great opportunity this early in my life to get involved in medicine and the pursuit of new treatments/cures, and I am incredibly appreciative. I shall put in whatever time and work it takes to help the world become at least one step closer to curing HIV-AIDS.

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