Hello, A new project on the LCRC cluster has been requested. Please forward the information on to the LCRC Allocation sub-committee. Applicant's name: David Tiede Applicant's institution: ANL Applicant's division: CSE Project Name: protein_e-wire2 Project title: Solar energy conversion in biomimetic molecular architectures Associated funding: This project is supported by three funding programs within the DOE-BES Division of Chemical Sciences, Geosciences, and Biosciences: i) Solar Photochemistry; ii) Photosynthetic Systems; iii) Energy Frontier Research Center: Argonne Northwestern Solar Energy Research (ANSER) Center Other Systems: N/A Science: This computational project will supplement our experimental work on construction and characterization of water-splitting catalysts and biomimetic molecular architectures for solar energy conversion. The first aim is to explore replica-exchange all-atom Molecular Dynamics (MD) simulations as a tool to achieve a better sampling and to predict impact of protein mutations and chemical modifications on conformational dynamics and structural stability with various photosensitizers and photosensitizer-catalyst dyads covalently linked to PpcA, a multi-heme c-type cytochrome from Geobacter sulfurreducens. These results will facilitate interpretation of kinetic electron transfer rates as well as Small- and Wide-Angle X-ray Scattering (SAXS, WAXS) as well as NMR data to provide an insight into strategies for optimization of electron transfer rates within biomimetic hybrids. The second aim is to use replica-exchange MD to simulate equilibrium positions and dyna mics of mutations needed in order to tune redox potentials of PpcA hemes. Our third goal is to use several types of ligand docking simulations to screen and optimize ligand binding sites on PpcA protein surface. Project description: We are developing biomimetic molecular architectures for efficient solar energy conversion using artificial and natural photosensitizers combined with natural and genetically engineered host systems capable to support long-lived charge-separated states and conduct charges away from the photosensitizers. We recently significantly expanded a series of cysteine mutants of PpcA, a multiheme redox protein from Geobacter sulfurreducens, and synthesized a number of photosensitizers which can be selectively attached to the engineered residues. These bio-hybrids demonstrate an unexpectedly wide range (2x107-5x1011 s-1) of light-induced electron transfer (ET) rates. However, the precise targeted control of charge transfer rates and quantum yields remain elusive. Furthermore, there is no agreement in scientific community on whether the donor-acceptor distance, driving and re-organization energies are the only factors responsible for control of ET rates (Moser e t al. Nature, 355:796; Page et al. Nature, 402:47) or frameworks of internal bonds and protein dynamics can also have a significant impact on the ET in protein systems (Balabin and Onuchic, Science, 290:114; Lin et al. Science, 310, 1311). In the past we have developed CHARMM force field parameters for several photosensitizers and obtained promising preliminary results for some of PpcA mutants in their oxidized form linked to Ru(bpy)3 which closely matched X-ray scattering data. However, in some instances the complete equilibration of photosensitizer-cytochrome complexes required 50-75 ns trajectories and a lingering question remained whether 200-300ns simulations were sufficient. In FY2016 our main focus will be on obtaining a better sampling of possible conformers with replica-exchange molecular dynamics. We expect that MD simulations will provide a sufficient sampling of protein conformational space and help us to better rationalize the collected kinetic data on charge transfer rates and SAXS/WAXS scattering profiles as well as the observed perturbations in NMR data. To achieve this goal we plan to run a series of 100-500 ns MD simulations on selected PpcA mutants. At the initial stages of the project we wil l focus on the systems with all three PpcA hemes either oxidized or reduced. The latter is particularly interesting as it results in a significant change of the total protein change from +4 to +1. All MD simulations will be performed with NAMD 2.8 and CHARMM force field. We will use standard for protein MD conditions: nPT, PME electrostatics, explicit TIP3 water boxes sufficiently large to keep interaction energy negligible between protein mirror images. The analysis of MD trajectories, computational docking and calculation of X-ray scattering profiles will be carried out on our lab computers. The second goal is to use several rigid and flexible ligand docking approaches in order to predict and optimize binding sites for a new generation of photosensitizers and photosensitizer-catalyst dyads. We will continue to use an MPI version of DOCK6. We previously successful used this code on Blue and it already resulted in one peer-reviewed publication. NAMD is a highly scalable molecular dynamics simulations code. Our past benchmarks on Blues with PpcA in a water box (~13,000 atoms) showed more than 99% speed-up efficiency with ~1,600 atoms/CPU core and ~80% efficiency with ~400 atoms/core and yielded 5.1 and 15.7 ns/day on 8 and 32 cores, respectively. DOCK 6 typically had more than 95% scaling efficiency on 32-128 cores used in our previous work and we expect to get similar scaling figures with new simulations Industry partnership: Project URL: Requested allocation: 950000 Q1: 250000 Q2: 250000 Q3: 250000 Q4: 200000 Justification: NAMD is a highly scalable molecular dynamics simulations code. Our past benchmarks on Blues with PpcA in a water box (~13,000 atoms) showed more than 99% speed-up efficiency with ~1,600 atoms/CPU core and ~80% efficiency with ~400 atoms/core and yielded 5.1 and 15.7 ns/day on 8 and 32 cores, respectively. DOCK 6 typically had more than 95% scaling efficiency on 32-128 cores used in our previous work and we expect to get similar scaling figures with new simulations. Storage requirements: The requester has used undetermined amount hours of their initial startup project. In addition to approving an initial amount, please specify a Category and Subcategory for this project. For a list of the current selection of approved categories, please see: https://wiki.lcrc.anl.gov/wiki/Processes/Categories Once the Allocation committee has approved the project, please go to the Project Management page to create it: https://accounts.lcrc.anl.gov/projects.php Thank You, The LCRC Accounts System