Hello, A change in allocation has been requested: Requester: roux (Benoit Roux) Project: Drude Title: Development and validation of new polarizable force field for molecular dynamics Description: At the present time, MD simulations are not only limited by the computational resources but also by the physical correctness and accuracy of the underlying atomic models. Without a systematic approach to generate, test and validate the accuracy of the force fields, the value of MD simulations will always remain in question. The development of potential functions for computer simulations has a long history and is still a very active field. Essentially all of the MD simulations of complex molecular systems (biological or not) are currently carried out using fixed-charge non-polarizable force fields, even though there is a broad consensus that electronic polarization effect ought to be included. The important role of polarization is particularly obvious for self-assembling amphiphilic molecules, containing polar or charged groups as well as nonpolar moieties (see below). A number of research groups are working at developing new algorithm to treat polarization, eit her with inducible point dipoles, fluctuating charges, or classical Drude oscillators. The latter approach, which we have adopted, is the most advantageous due to its simplicity and computational efficiency. In this project, we will establish a protocol to automatically optimize the parameters of the molecules of interest using simulations. We will develop a global derivative-free optimization optimization search method to drive the parameter search relying on information from the large scale simulations. This procedure will involve a parallelized Hamiltonian-Replica exchange algorithm. The goal is to develop, optimize, and validate the functional form and parameters of a new force field accounting for induced polarization in molecular dynamics simulations must be for a range of biomolecular systems (lipid membranes, protein in solution, liquid phases, etc...). # computational methods The computational method involves ab initio quantum mechanics, as well as classical molecular dynamics simulations and free energy perturbation. The induced polarization is represented by introducing a small auxiliary charged particle attached to the nucleus by a spring. The pair forms a Drude oscillator. It can be shown that this construction accounts properly for the physics of induced polarization in molecular interactions. # scalability issues The new force field is developed to be implementable in a wide range of existing molecular dynamics codes. Currently, the model is supported by CHARMM, which has modest scalability. Our initial implementation of the methods in NAMD has allowed to run some benchmark systems with 75,000 water molecules with the polarizable force field. These NAMD simulatinos scale up to 1,000 cores without problems. # experiments planned We must simulate fully hydrated bilayer and monolayer membranes of DPPC, DPPE, DOPC and POPC and PS to optimized the force field for phospholipid molecules. To increase the sampling, we will probably run those simulations in parallel-parallel mode with replica-exchange MD simulations. The planned tests on the large solvated systems are absolutely necessary. We are also developing ion solvation models in liquid N-methylacetamide. # software requirements We use Gaussian, Qchem, CHARMM, NAMD. # sizes of calculations run on and/or planned for Jazz or other systems On single MD runs, we expect to use up to 64 cores in parallel. On replica-exchange MD runs, we could easily use up to 512 cores or more. Each of the simulations are expected to require about several weeks non-stop. # expected number of project members The number of members is expected to be 5-6, including Benoit Roux, Yun Luo and Albert Lau and Janamejaya Chowdhary Chris Rowley, from University of Chicago. Current: undetermined amount Justification: MD simulation of lipid membrane bilayers with the polarizable force field . The rate is 1.5 days/ns with 256 cores, for a total of 4,608 SUs for each system. We have to examine different sets of parameters to optimize the lipid force field. Each must be simulated for about 5-10 ns, which amounts to a total of 300,000 SUs. MD simulation of ion solvation with the polarizable force field in N-methylacetamide (NMA) and water for 3 alkali ion, 4 alkali earth, and 6 transition metals. The rate is 3 days/ns with 64 cores, for a total of 4,608 SUs for each system. There are 13 systems total, yielding 60,000 SUs. Ab initio calculations on NMA-Ion clusters using the program Gaussian. Here we mainly carry out geometry optimization with different level of theories: DFT hybrid, DFT pure, DFT+D, and the most computationally expensive, RI-MP2. We have to optimize about 80 clusters (different ions with different numbers of NMA and configuration around the ion) with each level. This amounts to a total of 60,000 SUs. Requested: 300000 A specific reason has been given: This is a very active project with 5 people currently involved. This is a key year for the development of the force field because we are almost done. This needs to be approved and the final allocation amount decided upon. Thank You, The LCRC Accounts System