(gc3569)Multiscale Modeling of Biochip Systems
EMSL Project ID
3569
Abstract
Biochips, of the microarray type, are fast becoming the default tool for combinatorial chemical and biological analysis in environmental and medical studies. The goal of this project is to use multiscale computational techniques to understand the basic physics and chemistry of these types of systems.Multiscale simulation techniques use simulations on a shorter length and time-scale to generate the input parameters for simulations on longer time-scales and this technique is ideally suited to the biochip problem. In this procedure, data from a molecular dynamics simulation of a reduced representation of a biochip, for example a single duplex DNA tethered to a surface, can be used to generate parameters for an elastic-body and/or Langevin calculation which includes more than one DNA duplex. The Langevin calculation in turn can be used to parameterize a Navier-Stokes simulation. The number of atoms and the time required to run a molecular dynamics simulation to obtain the same information is prohibitive.
In this project the molecular dynamics simulation techniques will be improved by including a fine grain overlapped Fourier optimized fast multipole algorithm for determining the inter-atomic potential and forces. In any molecular dynamics simulation the evaluation of the forces mandates the biggest computational effort. Any improvements in the CPU effort of these calculations also improve the size and the length of the dynamics simulations.
To change to a different time scale for the modeling calculations another technique that imitates flow phenomena is also under development. This project involves the design and creation of a computer program to simulate the sedimentation and hydrodynamic flow of a body in an incompressible viscous fluid. Currently, a simulation of a two-dimensional system composed of three spheres in an incompressible viscous fluid has been successfully completed on a single processor machine. Transfer to a parallel architecture will allow expansion of these calculations in time scale, number of particles, and number of degrees of freedom.
Finally, once these calculations are completed they are usually left on some sort of storage device accessible to one or a few limited research groups. Because these calculations are time consuming it is neither feasible nor easy for them to be rerun. The scientific community would greatly benefit from data locked in these simulations; not just those of this research collaboration but also other simulation data from other research groups. A simulation database that catalogs and makes accessible these simulations is the final aspect of this project. Data can be checked into the system by the research group that performs the calculations but are available, via a GUI front-end, to the entire community. Tools are included in the system for displaying of PDB files, performing analyses of the data, etc. The design is purposely modular ? other programs can be added as the need arises. An example of the use of a system like this would be computer-aided drug design. Average structures from a molecular simulation can be retrieved from the simulation database and used for a subsequent molecular docking experiment in the drug-design process.
Project Details
Project type
Capability Research
Start Date
2003-10-01
End Date
2006-10-08
Status
Closed
Released Data Link
Team
Principal Investigator
Team Members
Related Publications
B. Montgomery Pettitt, Arnold Vainrub, and Ka-Yiu Wong. DNA Saline Solutions Near Surfaces: Design Parameters of DNA Arrays, pages 381-393. Kluwer Academic Press, 2005
Chen C, BW Beck, K Krause, TE Weksberg, and BM Pettitt. 2006. "Effects of Dimerization of Serratia marcescens Endonuclease on Water Dynamics." Biopolymers 85(3):241-252.
Choudhury N, and BM Pettitt. 2005. "On the Mechanism of Hydrophobic Association of Nanoscopic Solutes." Journal of the American Chemical Society 127(10):3556-3567.
C. Y. Chen, B. W. Beck, K. Krause, and B. M. Pettitt. Solvent participation in Serratia marcescens endonuclease complexes. Proteins-structure Function Bioinformatics, 62:982-995, 2006
Graham L. Randall, B. Montgomery Pettitt, Gregory R. Buck, and E. Lynn Zechiedrich. Electrostatics of dna-dna juxtapositions: consequences for type ii topoisomerase function. Journal of Physics: Condensed Matter, 18:173-185, 2006
Hu CY, GC Lynch, H Kokubo, and BM Pettitt. 2010. "Trimethylamine ?-oxide Influence on the Backbone of Proteins: An Oligoglycine Model." Proteins. Structure, Function, and Bioinformatics 78(3):695-704. doi:10.1002/prot.22598
Hu CY, H Kokubo, GC Lynch, DW Bolen, and BM Pettitt. 2010. "Backbone Additivity in the Transfer Model of Protein Salvation." Protein Science 19(5):1011-1022. doi:10.1002/pro.378
J. Kurzak and B. M. Pettitt. Fast multipole methods for particle dynamics. Molecular Simulation, 32:775-790, 2006
J. Kurzak and B. M. Pettitt. Massively parallel implementation of a fast multipole method for distributed memory machines. J. Parallel Distributed Computing, 65:870-881, 2005
Kokubo H, and B Pettitt. 2007. "Preferential Solvation in Urea Solutions at Different Concentrations: Properties from Simulation Studies." Journal of the American Chemical Society 111(19):5233-5242. doi:10.1021/jp067659x
Kurzak J, and B Pettitt. 2005. "Communications Overlapping in Fast Multipole Particle Dynamics Methods." Journal of Computational Physics 203(2):731-743. doi:10.1016/j.jcp.2004.09.012
N. Choudhury and B. M. Pettitt. Dynamics of water trapped between hydrophobic solutes. J. Phys. Chem. B, 109:6422-6429, 2005
N. Choudhury and B. M. Pettitt. Local density profiles are coupled to solute size and attractive potential for nanoscopic hydrophobic solutes. Mol. Simulation, 31:457-463, 2005
Niharendu Choudhury and B. Montgomery Pettitt. Enthalpy-entropy contributions to the potential of mean force of nanoscopic hydrophobic solutes. Journal of Physical Chemistry B, 110:8459-8463, 2006
Niharendu Choudhury and B. Montgomery Pettitt. The dewetting transition and the hydrophobic effect. J Am Chem Soc, 129:4847-4852, 2007
Weksberg TE, GC Lynch, K Krause, and B Pettitt. 2007. "Molecular Dynamics Simulations of Trichomonas vaginalis Ferredoxin Show a Loop-Cap Transition." Biophysical Journal 92:3337-3345. doi:10.1529/biophysj.106.088096
Wong K, and B Pettitt. 2004. "Orientation of DNA on a Surface from Simulation." Biopolymers 73:570-578.