NCSI: Alchemical Perturbation Simulations to Study the Lipid Specificity in PLAFP

Status	Completed
Mentor Name	Josh Vermaas
Mentor's XSEDE Affiliation	Research Allocation
Mentor Has Been in XSEDE Community	4-5 years
Project Title	Alchemical Perturbation Simulations to Study the Lipid Specificity in PLAFP
Summary	Ongoing experimental work has shown that the plant signaling protein PLAFP specifically binds to phosphatidic acid (PA) headgroups to transport these signaling lipids through the plant phloem. Prior simulation work has shown how phosphatidic acid binds to PLAFP. Our research goal here is to carry out alchemical free energy calculations to determine the free energy of binding for phosphatidic acid relative to other phospholipids.
Job Description	Using VMD and under postdoctoral supervision, the student will start from PA bound structures, and use alchemical methods to compute the free energy difference when PA is transformed to other phospholipid head groups. The student will spend 8-10 hours per week: -Setting up simulations -Transferring files to supercomputing centers -Performing simulations -Analyzing the results using ParseFEP -Participating in group activities to learn about other molecular dynamics methods (eg. group meetings)
Computational Resources	We anticipate the first round of simulations will be tested locally, on the MSU HPCC resources the lab has bought into. Extension for these simulations will be carried out using the group’s XSEDE allocation, principally on the NCSA Delta resource where more GPUs are available.
Contribution to Community	Where I see the greatest value for this project within the larger computational biology ecosystem is to provide opportunity for diverse researchers to gain experience and training when they otherwise might be excluded. Many computationally-oriented domestic graduate students that XSEDE typically reaches look like me (white and male). Expanding the talent pool beyond this subpopulation is going to be advantageous for the community, and improve research quality going forward.
Position Type	Intern
Training Plan	The named student and the postdoc leading the PLAFP project have a good working relationship from the current semester working on the XSEDE-supported nanowire project going on in the group. While the previous semester detailed the inner workings of umbrella sampling methods for calculating free energy, the proposal furthers the students education through introducing them to alchemical methods. What has worked for the student to date are two 1-2 hour meetings per week (one group meeting + 1 one-on-one meeting) to discuss project progress. We also communicate via slack to alleviate any immediate questions that would otherwise impede progress.
Student Prerequisites/Conditions/Qualifications	Prior experience with VMD, NAMD, and the unix command line are essential to be able to carry out alchemical simulation preparation and analysis.
Duration	Semester
Start Date	01/03/2022
End Date	04/30/2022