NCSI: Testing Supervised Molecular Dynamics for Curved Access Channels in p450

Status	Completed
Mentor Name	Edward Ackad
Mentor's XSEDE Affiliation	Startup Allocation
Mentor Has Been in XSEDE Community	4-5 years
Project Title	Testing Supervised Molecular Dynamics for Curved Access Channels in p450
Summary	There are only a few hypotheses of how the drugs actually enter the enzyme in order to be metabolized. This question has implications for drug-drug interactions (effects when you need to take multiple medications) as well as drug design and discovery. This project will develop scripts to run Supervised Molecular Dynamics (SuMD) for the ingress of atorvastatin lactone (ARVL), and take preliminary data.
Job Description	The student will develop collective variables to try and "guide" ligand through various tunnels in p450 using NAMD. These will be evaluated for success by the student and adjust to work, and be optimized for each channel. The student will also run the simulations on the Bridges.
Computational Resources	Bridges regular memory 10000 SU and the Physics Department GPU cluster.
Contribution to Community	Our work will continue to show the value in computational biophysics and how it can ask and answer scientific questions not yet possible experimentally. This will allow the community to continue showing that its roll in the Biology Century is pivotal and that clever techniques (such as SuMD) can leverage current hardware to obtain results at timescales not possible for another 5-10 years with standard techniques (conventional MD).
Position Type	Intern
Training Plan	The student will spend the first two weeks learning the basics of steered MD (through the NAMD tutorial) and test runs on XSEDE. Then the student will learn drag the drug to be within the membrane. The student will then start from that snapshot and attempt to use Supervised MD to see the start of the drug's ingress. The student will use progesterone since it is a mostly linear drug and attempt to have it guided to the channels which open in the membrane.
Student Prerequisites/Conditions/Qualifications	Intermediate experience with any programming language and Linux.
Duration	Semester
Start Date	08/15/2021
End Date	12/15/2021