Hello, A yearly allocation for the LCRC cluster has been requested with the following updated information: Submitter/PI: Benoit Roux Project Name: Drude Division: BIO Project title: Development and validation of new polarizable force field for molecular dynamics Associated funding: LDRD on force field with Subramanian Sankaranarayanan (number not out yet) NIH grant from NIGMS R01-GM072558: Polarizable Force Field For Proteins and Lipids Other Systems: BG/P, XSEDE, Anton, kbt, Beagle, Blue Waters Science: The functional form and parameters of a new force field accounting for induced polarization in molecular dynamics simulations must be developed, optimized, and validated for various biomolecular systems. We are mainly interested in ions binding to proteins at this point. Project description: Ions play indispensable roles in the structures and functions of biologically important molecules, many biological processes are also found to be ion-specific. Thorough interpretations of such ion-specificity require models that accurately treat electrostatic interactions between ions and their biological environments, which often involve polarization effects at different magnitudes. In the past several years, a significant number of studies have been published in scientific journals investigating the ion-protein interactions. A large portion of these molecular dynamics (MD) simulations are based on force fields using simple-point representations for one atoms or even for the entire chemically/physically importation groups, for example, the CHARMM, OPLS, GROMOS, and the AMBER force fields. Limitations are often seen in MD simulations employing these force fields and cannot be improved by further parameterization. Due to their underlying assumption of the fixed interaction-potential function, these models are not capable of reflecting the polarizable nature of atoms and thus failed in the cases when the polarization effects are prominent. Towards the goal of providing a comprehensive and accurate description for the behaviors of ions interacting with macromolecule, in the next allocation cycle, we will focus on improving polarizable ion force fields based on the classical Drude oscillator models. The Drude polarizable force field has been implemented in the program NAMD. It runs efficiently, at a computational cost comparable to that of non-polarizable force fields (slower only by a factor of about 1.4). This study will provide a systematic protocol by employing a wide range of target data. Besides the conventionally employed benchmarks in parameterization such as the gas-phase ion-small molecular cluster interactions and the experimental measured condensed-phase properties, the proposed study will also incorporate QM binding energy calculations for a wide spectrum of proteins. Specifically, we will improve models for biologically important ions interacting with proteins, including the alkali cation Na+, K+, a lkaline earth metal cations Ca2+, Mg2+, and transition metals Zn2+ and Ba2+. In addition, we hope that the approach employed will help initiating and facilitating a systematical approach for evaluating force field performances, thus allowing scientists resolving the functions and behaviors of ions in biological systems more efficiently and with higher confidence. In the propose study, we will perform MD simulations and QM interaction energy calculations for a large number of ion-binding proteins (10 different proteins for each ion type) and utilize these data as the benchmarks in the parameter optimization process. Allocation on fusion at LCRC of the Argonne National Lab is therefore requested to accomplish this project. Industry partnership: Project URL: http://thallium.bsd.uchicago.edu/RouxLab/ Current FY Hours Used: undetermined amount New FY Requested allocation: 1000000 Q1: 250000 Q2: 250000 Q3: 250000 Q4: 250000 Justification: We are mainly using Gaussian to compute binding energies of ion to proteins sites from a set of configurations previously generated with classical molecular dynamics. On average these configurations have 50-100 atoms, so the QM calculations are substantial. While the computations are extensive, Gaussian runs well on fusion and it well optimized. Storage requirements: 100 GB Thank You, The LCRC Accounts System