Skip to main content
Log in

Abstract

Point mutation of amino acids is a means used by biotechnologists to improve the performance of proteins. To study a point-mutated polypeptide, one requires its global minimum energy conformation. This conformation can be determined by molecular dynamics via Langevin's equations of motion. Molecular dynamics simulations belong to the most difficult problems to parallelize in a scalable manner. We provide a method for defining a special purpose 3D array processor architecture for the molecular dynamics simulation of point-mutated polypeptides. The architecture is derived from a spatial decomposition of a known conformation of the point-mutated polypeptide or the native conformation of the given protein. By using an approximation scheme for the deterministic forces, the interprocessor communication can be kept local. The architecture affords a simple distributed load balancer and is scalable. The computational workload of the array processor architecture to perform molecular dynamics simulations under realistic conditions is addressed. An example architecture is given by point-mutated penicillin amidase.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. T.E. Creighton, Proteins: Structures and Molecular Principles, New York: Freemann, 1983.

    Google Scholar 

  2. M.P. Allen and D.J. Tildesley, Computer Simulation of Liquids, Oxford: Clarendon Press, 1987.

    Google Scholar 

  3. A.R. Leach, Molecular Modelling: Principles and Application, Addison Wesley, 1996.

  4. B. Brooks, R. Bruccoleri, B. Olafson, D. States, S.Swaminathan, and M. Karplus, "CHARMM: A Program for Macromolecular Energy Minimization and Dynamics Calculations," Dept. of Chemistry, Harvard Univ., 1982.

  5. A. Lyubartsev and A. Laaksonen, "MDYNAMIX-A Scalable Portable Parallel MD Simulation Package for Arbitrary Molecular Mixtures," Comp. Phys. Comm., vol. 128, 2000, pp. 565-589.

    Article  MATH  Google Scholar 

  6. S.J. Weiner, P.A. Kollman, D.A. Case, U.C. Singh, C. Ghio, G. Alagona, S. Profeta, and P. Weiner, "A New Force Field for Molecular Mechanical Simulation of Nuclear Acids and Proteins," J. Am. Chem. Soc., vol. 106, 1984, pp. 765-784.

    Article  Google Scholar 

  7. R.K. Brunner, J.C. Phillips, and L.V. Kale, "Scalable Molecular Dynamics for Large Biomolecular Systems," Preprint Dept. Computer Science, Urbana Univ, Il, 2000.

  8. M. Nelson, W. Humphrey, A. Gursoy, A. Dalke, L. Kale, R.D. Skeel, and K. Schulten, "NAMD-A Parallel Object-Oriented Molecular Dynamics Program," Int. J. Supercomput. Applic. High Performance Computing, vol. 10, 1996, pp. 251-268.

    Article  Google Scholar 

  9. S. Plimpton and B. Hendrickson, "A New Parallel Method for Molecular Dynamics Simulation of Macromolecular Systems," J. Comput. Chem., vol. 17, 1996, pp. 326-337.

    Article  Google Scholar 

  10. M. Eichinger, H. Grubm¨uller, and H. Haller, "User Manual for EGO VIII (Release 2.0)," Leibniz Rechenzentrum, Munich, 2000.

  11. C.B. Anfinsen, E. Haber, M. Sela, and F.H. White Jr., Proc. Natl. Acad. Sci., vol. 47, 1961, pp. 1309-1314.

    Article  Google Scholar 

  12. G. Nemethy, M.S. Pottle, and H.S. Scheraga, "Energy Parameters in Polypeptides. Updating the Geometric Parameters, Nonbonded Interactions and Hydrogen Bond Interactions for the Naturally Occurring Amino Acids," J. Phys. Chem., vol. 87, 1983, pp. 1883-1887.

    Article  Google Scholar 

  13. A. Liwo, "AUnited-Residue Force Field for Off-Lattice Protein-Structure Simulations. I. Functional Forms and Parameters of Long-Range Side-Chain Interaction Potentials from Protein Crystal Data," J. Comp. Chem., vol. 18, p.6.

  14. J.L. Klepeis and C.A. Floudas, "Deterministic Global Optimization and Torsion Angle Dynamics for Molecular Structure Prediction," Techn. Report, Dept. Chem. Eng., Princeton Univ., Princeton, NJ.

  15. A. Neumaier, "Molecular Modelling of Proteins and Mathematical Prediction of Protein Structure," SIAM Rev., vol. 39, 1997, pp. 407-460.

    Article  MathSciNet  MATH  Google Scholar 

  16. H.A. Scheraga, "Recent Developments in the Theory of Protein Folding: Searching for the Global Energy Minimum," Biophys. Chem., vol. 59, 1996, pp. 329-339.

    Article  Google Scholar 

  17. W.F. van Gusteren and H.J.C. Berendsen, "Computer Simulation of Molecular Dynamics: Methodology, Applications, and Perspectives in Chemistry," Angew. Chemie Int. Ed. in English, vol. 29, 1990, pp. 992-1023.

    Article  Google Scholar 

  18. L. Hewitt, V. Kasche, K. Lummer, R.J. Lewist, G.N. Marshudov, C.S.Verma, G.G. Dodson, and K.S.Wilson, "Structure of a Slow Processing Precursor Penicillin Acylase from Escherichia coli Reveals the Linker Peptide Blocking the Active Site Cleft," J. Mol. Biology, vol. 302, 2000, pp. 887-898.

    Article  Google Scholar 

  19. V. Kasche, K. Lummer, A. Nurk, E. Piotraschke, A. Rieks, S. Stoeva, and W. Voelter, "Intramolecular Proteolysis Initiates the Maturation of Penicillin Amidase from E. coli. Biochem. Biophys. Acta, vol. 1433, 1999, pp. 76-86.

    Google Scholar 

  20. L. Hewitt, V. Kasche, K. Lummer, R.J. Lewist, G.N. Marshudov, C.S.Verma, G.G. Dodson, and K.S.Wilson, "ASlowProcessing Precursor Penicillin Acylase from Escherichia coli," PDB ID: 1E3A, PDB, 2000.

  21. K. Lummer, "Inter-und intramolekulare enzymatische Katalysierte Reaktionen am Beispiel der Penicillinamidase,"Dissertation, TU Hamburg-Harburg, 2000.

  22. K.-H. Zimmermann, T. Lai, Z. Ignatova, B. Galunsky, and V. Kasche, "Prediction of Point-Mutated Penicillin Amidase Precursor from Escherichia coli via Simulated Annealing," Preprint, 2002.

  23. K. Lehmann, "Molecular Dynamics of Proteins," Diploma Thesis, TU Hamburg-Harburg, 2002.

  24. S. Kirkpatrick, C.D. Gelatt, and M.P. Vecchi, "Optimization by Simulated Annealing," Science, vol. 220, 1983, pp. 671-680.

    Article  MathSciNet  Google Scholar 

  25. S.Y. Kung, VLSI Array Processors, Prentice Hall, 1987.

  26. K.-H. Zimmermann, "Linear Mappings of nDRecurrence Equations onto kD Array Processors," J. VLSI Signal Processing, vol. 12, 1996, pp. 187-202.

    Article  Google Scholar 

  27. K. Jainandunsing, "Optimal Partitioning Scheme for Wavefront/ Systolic Array Processors," Proc. IEEE Symp. on Circuits and Systems, 1986, pp. 940-943.

  28. K.-H. Zimmermann, "A Unifying Lattice-Based Approach for the Partitioning of Systolic Arrays via LPGS and LSGP," J. VLSI Signal Processing, vol. 17, 1997, pp. 21-42.

    Article  MATH  Google Scholar 

  29. M. Markiewicz, "Dipole Moments of Protein Structures," Project Work, TU Hamburg-Harburg, 2002.

  30. N.A. Lynch, Distributed Algorithms, San Francisco: Morgan Kaufmann, 1996.

    MATH  Google Scholar 

  31. H.M. Berman, J. Westbrook, Z. Feng, G. Gilliland, T.N. Bhat, H.Weissig, I.N. Shindyalov, and P.E. Bourne, "The Protein Data Bank," Nucleic Acids Res., vol. 28, 2000, pp. 235-242.

    Article  Google Scholar 

  32. Intel Itanium 2: www.intel.com

  33. H. El-Rewini and T.G. Lewis, Distributed and Parallel Computing, Manning, Greenwich, CT, 1997.

  34. T.T. Lai, "Implementing a Simulated Annealing Algorithm for the Prediction of Point-Mutated Penicillin G Acylase," Master Thesis, TU Hamburg-Harburg, 2001. A Special Purpose Array Processor Architecture 309

  35. N. Metropolis, A.W. Rosenbluth, A.H. Teller, and E. Teller, "Equation of State Calculation by Fast Computing Machines," J. Chem. Physics, vol.21, 1953, pp. 1087-1091.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zimmermann, KH. A Special Purpose Array Processor Architecture for the Molecular Dynamics Simulation of Point-Mutated Proteins. The Journal of VLSI Signal Processing-Systems for Signal, Image, and Video Technology 35, 297–309 (2003). https://doi.org/10.1023/B:VLSI.0000003027.47559.1e

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1023/B:VLSI.0000003027.47559.1e

Navigation