TR&D3: Brownian Mover DBP4: Biosensors

Transcription

1 TR&D3: Brownian Mover DBP4: Biosensors Aleksei Aksimentiev Lead co-investigator of TR&D3-BD and DBP4 Associate Professor of Physics, UIUC

2 TR&D3 Brownian Mover Overview Brownian dynamics Dispensing with solvent degrees of freedom orders of magnitude computational efficiency improvement Larger systems (µ m) Longer time scales (ms s) Earlier Brownian dynamics studies Protein-protein docking 10 Å! A. Elcock, D. Sept, J. McCammon, J. Phys. Chem. B, 2001 Hydrodynamic effect on crowded cellular systems 40 Å! 1. Complements existing software with capabilities to perform ms simulations of million-particle micron-size systems. 2. Provides tools for obtaining potentials of mean force and diffusivity maps with accuracy of all-atom MD. 3. Uses the power of NAMD to achieve efficient parallelization. T. Ando, J. Skolnick, PNAS, Includes tools for parameterization of novel systems. Protein diffusion in the cytosol 200 Å! 5. Contributes a database of ready-to-use computational models of typical biomolecular systems. S. McGuffee, A. Elcock, PLOS Computational Biology, 2010

3 Unique features of the Brownian Mover 3 Similar programs that already exist: BrownDye J.A. McCammon UHBD, SDA, MacroDox, Brownmove V. Helms BD_BOX J. Trylska In comparison with the above programs Brownian Mover will: o Bring atomic accuracy into Brownian dynamics simulations. o Simulate µm-size systems of 10 7 particles on ms - s time scales. o Employ NAMD framework o Utilize a broad range of potentials. Poisson-Boltzmann, tabulated, 3D potentials of atomic resolution o Have the ability to: Perform open systems simulations (variable number of particles) Use multi-scale dynamic force and diffusion grids Account for hydrodynamic interactions (lattice Boltzmann, stochastic rotation dynamics) o Provide built-in tools for setup, analysis and visualization of trajectories o Offer a database of ready-to-use potentials

4 Overview of Brownian Mover modules 4 Current state of module development PROTOTYPE AVAILABLE UNDER DEVELOPMENT

5 Recent publication of methodology 5 Predicting the DNA Sequence Dependence of Nanopore Ion Current Using Atomic-Resolution Brownian Dynamics J. Comer and A. Aksimentiev, J. Phys. Chem. C, 2012, 116 (5), All-atom MD 3D potentials of mean force Brownian dynamics Position-dependent diffusivity Preserved atomistic details Referee response: This stunning manuscript by Comer and Aksimentiev focuses on a new method of calculating the ion transport through a nanopore. [ ] This manuscript certainly deserves immediate publication since it is among the top publications if not the top one which I readbtrc thisforyear. Macromolecular Modeling and Bioinformatics

6 Brownian Mover summary 7 Brownian Mover strengths Brownian Mover will use NAMD framework, which provides: ü Efficient dynamic load balancing ü Extensive library of simulation protocols ü Scripting interface ü Multi-resolution dynamic grid forces ü Simple input/output routines ü User-friendly documentation Brownian Mover scientific role ü Brownian Mover can perform simulations of µmsize biological systems on ms time scales at a tremendously lower computational price ü Developed methods and tools allow Brownian Mover to preserve atomistic details of all-atom MD Brownian Mover development goals 1. Make millisecond simulations of million particle systems accessible to mainstream researchers 2. Enable realistic simulations of cellular environment 3. Facilitate innovations in the field of biomedical nano- and microdevices 4. Aid discoveries by providing tools for parameterization of novel systems 5. Service modeling community with ready-to-use computational models of typical biomolecular systems