BLOG 4: Final Blog Post

Unfortunately with COVID-19 taking over and closing school, most of the research work we had done could not be completed. This semester I got the chance to work with Professor Deng on finding drug candidates to screen against the HIV virus. We started the year using molecular dynamics and programs such as “Amber Tutorials” to assist us. Throughout the semester, research did not go as planned and I ended up reading articles and research papers on my topic to better understand how previous researchers analyzed data and targeted the virus. 

Drug discovery is very important in today’s society as new healthcare issues arise new drugs are needed. Structure based drug design is one of the very few techniques that uses 3D structures to target receptor proteins. Structure based drug design was introduced in the late 1970s, scientists did not have many resources or computational methods at that time and had to stick to combining chemical synthetic methods and factorial screening. Nowadays, computer based drug design is used along with comparative models and being able to derive complex protein structures with the help of prior knowledge. Knowing the structure of the protein model lets scientist make changes to build a more effective drug. Protein binding can be reversed whether it involves hydrogen bonds, ionic bonds, or van der Waals forces. For example, a specific protein can have water molecules bounded and if the drug was redesigned to have electrostatic interactions we can change the way it binds in that specific area.There are four stages to drug discovery which include; discovery phase where the target gene is cloned,  developmental phase where you synthesize, optimize, and test for affinity as well as determine the 3D structure, and clinical trials which need to be passed before the structure can move onto the registry phase. MD stimulation play a huge role in designing drugs because they can track system behaviors with accuracy, provide flexibility, visuals of molecular processes as well as estimating binding energies.

blog 3: Difficulties with Charmm-GUI

Due to Professor Deng’s busy schedule, research has been setback for us while we work on molecular docking stimulations. We plan on continuing with Charmm-GUI this month. It is very important to understand that it is okay to have setbacks and to be patient while we try to work during this time. I know that we will be able to complete this project before the semester ends despite all the problems we have encountered.

Blog 2

These past few weeks, I have been working on familiarizing myself with molecular dynamics and understanding how big of a role they play with our research. Molecular dynamics is a computer based stimulation which helps analyze atoms and molecules that are moving and in which ways they interact with one another. This technique helps us work with protein models and experiment different methods of combining them. Protein modeling is a very effective way that helps obtain structural information before researchers start experimenting in labs. With the help of “Amber Tutorials” we can see the motion of protein models and be able to design different sets of proteins that are arranged in various ways with computer coding. MD stimulations aids in finding a more accurate model of the target protein and predict any changes in the function of the protein.

Dr.Deng has been very busy this semester so I have been working on reading up on how to use Amber and master all of its tutorials. I have ran into problems several times where the program either stops working or does not allow me to insert a certain set of codes therefore I ask Professor Deng for assistance and he is usually able to help me. Amber is not a very effective program but it is great for beginners to use and familiarize themselves with the coding language. Later on, we will start using better programs that aid us in protein stimulations.






Blog 1: Combining Docking and Molecular Dynamics- based free energy methods to improve computational screening of drug candidates against HIV integrase

Dr. Deng and I have been performing research to find better methods to improve screening of drug candidates against the HIV virus. We are using molecular dynamics and programs such as “Amber Tutorials” to help further guide us. Molecular dynamics is a computer based method to help us figure out how proteins fold and can bind to their targeted sites which is a crucial part of helping researchers figure out binding values for condensed directed locations. HIV is a human immunodeficiency virus that can destroy white blood cells and put one at risk for serious diseases/cancers. HIV integrase is a vital protein that will help us understand HIV’s role in the human body and how to target it specifically. We have been working on finding potential binding molecules of HIV integrase that will help predict ligand bound conformations and target proteins.

The past few weeks, we have been reading numerous articles/research papers and studying molecular dynamics to better understand how such viruses can be targeted. By practicing molecular dynamics simulations and analyzing data, we are getting one step closer to determining which drugs can bind easily. This research requires a lot of time and dedication because before using programs such as “Amber Tutorials”, one has to fully learn how it works and become comfortable with simple calculations and coding exercises. I have been able to apply previous knowledge to conduct docking simulations and analyze the protein models over the semester. I am excited to learn more throughout this school year and make it easier for other researchers to find drugs that can further prevent HIV related diseases.