Hello, A yearly allocation for the LCRC cluster has been requested with the following updated information: Submitter/PI: Maksym Kryvohuz Project Name: Quantum_catalysis Division: CSE Project title: Quantum effects in enzyme catalysis Associated funding: Director’s Fellowship Other Systems: None Science: The objective of this project is to perform modeling of hydrogen transfer step in several enzyme-catalyzed reactions, in which significant nuclear quantum effects were experimentally observed. The origin of high efficiency of enzymes as catalysts remains unclear, yet fundamental understanding of the mechanisms underlying the function of enzymes would assist in the design of bio-inspired synthetic catalysts. It has been suggested that nuclear quantum effects such as tunneling of hydrogen through the reaction barrier can contribute to the efficiency of enzyme catalysis, yet its role in catalysis is unclear. The results of this project will provide novel understanding of the role of quantum effects in enzyme catalysis and suggest ways to improve catalytic efficiency of bio-inspired synthetic catalysts. The proposed project supports Argonne’s M2D2 initiative of synthesis by design as well as on development of biomimetic catalysts for efficient conversion of biomass into fuels. Project description: In the previous fiscal year we have studied quantum effects of H-transfer step catalyzed by the MADH enzyme, and improved our own program code to make distributed computations more efficient. In the following year we plan to apply the developed code to model H-transfer step catalyzed by enzymes (a) Soybean Lipoxygenase-1 and (b) Aromatic Amine Dehydrogenase, in which large amount of hydrogen tunneling has been experimentally observed. Quantum effects of H-transfer step in enzyme catalyzed reactions will be studied via the instanton reaction rate theory [Kryvohuz, J. Chem. Phys. v.134, p.114103 (2011), v. 137, p. 234304 (2012), v. 138, p. 244114 (2013)] which allows one to rigorously incorporate nuclear quantum effects in multiple dimensions with on-the-fly computations of accurate electronic reactive potential energy surface (PES). About 50 atoms of the active site of enzymes will be treated quantum mechanically with electronic structure calculations of reactive PES performed in Gaussian09 package. The numerical algorithm is based on determination of tunneling trajectories under the multidimensional reaction barrier by optimization. The tunneling trajectory is divided in 16 points and its optimal shape is determined by variational principle together with on-the-fly calculations of PES at these 16 points. One round of optimization requires about 10 iterations, which results in the total number of 16*10=160 single-point electronic structure calculations (with frequency analysis, i.e., computation of matrix of second derivatives which is essential for the process of optimization) to find an optimized tunneling path at a single temperature. Tunneling trajectories at several temperatures (from 5 to 6 different values) need to be determined to obtain Arrhenius plot, which requires (160 configurations)*(5 temperatures)= 800 single point electronic structure calculations for a system of 50 atoms. Averaging over about 20 configurations of enzyme/solvent environment is necessary to get an average value of a canonical reaction rate constant. Thus (800 single point calculations)*(20 environment configurations) = 16000 single-point computations (with frequency analyses) constitute the typical number of computations required for one enzyme system, or 32000 single-point computations for studying two different enzymes. DFT mPW1K or B3LYP methods will be used for on-the-fly electronic struct ure calculations of PES. Numerical tests shown below indicate that an organic system of 45 atoms requires about 24 core-hours for a single job with frequency analysis. The estimated amount of allocation time for the project is therefore (24 core-hours)*(32000 computations) = 768,000 core-hours. Project URL: Current FY Hours Used: undetermined amount New FY Requested allocation: 768000 Q1: 192000 Q2: 192000 Q3: 192000 Q4: 192000 Justification: A test of performance of B3LYP and mPW1K methods with 6-31+G(d,p) basis for a frequency analysis of a fixed geometry 45-atom organic molecule (PAF-1 monomer), which contains 20 atoms of H and 25 atoms of C was performed with Gaussian 09 code using 8, 16, 24, and 32 cores. The performance results are summarized in the table below. Substantial speed-up is achieved with the increase in the number of cores. Nodes x Cores Wall Time (min) B3LYP mPW1K 1 x 8 159 172 2 x 8 82 91 3 x 8 58 62 4 x 8 45 49 Thank You, The LCRC Accounts System