Frontiers in High-Performance, Large-Scale Molecular Dynamics. 35 Years of Molecular-Dynamics Simulations of Biological Systems

doi:10.6023/A12110930

Abstract

The main thrust of this contribution is to review applications of numerical simulations to biological systems over the past 35 years-specifically classical molecular-dynamics simulations and related preferential sampling approaches aimed at exploring selected degrees of freedom of the molecular assembly. Arguably enough, structural biology and biophysics represent one of the greatest challenges for molecular dynamics, owing to the size of the biological objects of interest and the time scales spanned by the molecular processes of the cell machinery in which these objects are prominent actors. The reader is assumed to be fully familiarized with the basic theoretical underpinnings of molecular-dynamics simulations, which will be discussed here from a biological standpoint, emphasizing how the enterprise of modeling increasingly larger molecular assemblies over physiologically relevant times has shaped the field. This review article will further show how the unbridled race to dilate both the spatial and the temporal scales, in an effort to bridge the gap between the latter, has greatly benefitted from groundbreaking advances on the hardware, computational front-notably through the development of massively parallel and dedicated architectures, as well as on the methodological, algorithmic front. The current trends in this research field, boosted by recent, cutting-edge achievements, wherein molecular dynamics has reached new frontiers, provide the basis for an introspective reflection and a prospective outlook into the future of biologically-oriented, high-performance numerical simulations. Furthermore, alternatives to brute-force molecular dynamics towards connecting time and size scales will be discussed, in particular a class of approaches relying upon the preferential sampling of judiciously chosen, important degrees of freedom of the biological object at hand. These methods, targeted primarily at providing a detailed thermodynamic picture of the molecular process at hand, can be viewed as computational tweezers designed to dissect the latter by means of a reduced set of collective variables.

Key words: molecular dynamics simulations, biological systems, theory and algorithms, high-performance and large-scale calculations, time and size scales

Cite this article

Cai Wensheng, Christophe Chipot. Frontiers in High-Performance, Large-Scale Molecular Dynamics. 35 Years of Molecular-Dynamics Simulations of Biological Systems[J]. Acta Chimica Sinica, 2013, 71(02): 159-168.

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References

[1] Lee, E. H.; Hsin, J.; Sotomayor, M.; Comellas, G.; Schulten, K. Structure 2009, 17, 1295.

[2] Dror, R. O.; Jensen, M. ?.; Borhani, D. W.; Shaw, D. E. J. Gen. Physiol. 2010, 135, 555.

[3] Alder, B. J.; Wainwright, T. E. J. Chem. Phys. 1957, 27, 1208.

[4] Chipot, C. In Nanoscience: Nanobiotechnology and Nanobiology, Eds: Boisseau, P.; Lahmani, M.; Houdy, P., Springer, Heidelberg, Dordrecht, London, New York, 2009.

[5] Verlet, L. Phys. Rev. 1967, 159, 98.

[6] Brooks, B. R.; Bruccoleri, R. E.; Olafson, B. D.; States, D. J.; Swaminathan, S.; Karplus, M. J. Comput. Chem. 1983, 4, 187.

[7] Weiner, S. J.; Kollman, P. A.; Case, D. A.; Singh, U. C.; Ghio, C.; Alagona, G.; Profeta Jr., S.; Weiner, P. J. Am. Chem. Soc. 1984, 106, 765.

[8] Izvekov, S.; Voth, G. A. J. Phys. Chem. B 2005, 109, 2469.

[9] Marrink, S. J.; Risselada, H. J.; Yefimov, S.; Tieleman, D. P.; de Vries, A. H. J. Phys. Chem. B 2007, 111, 7812.

[10] Klein, M. L.; Shinoda, W. Science 2008, 321, 798.

[11] Villa, E.; Sengupta, J.; Trabuco, L. G.; LeBarron, J.; Baxter,W. T.; Shaikh, T. R.; Grassucci, R. A.; Nissen, P.; Ehrenberg, M.; Schulten, K.; Frank, J. Proc. Natl. Acad. Sci. U. S. A. 2009, 106, 1063.

[12] Allen, M. P.; Tildesley, D. J. Computer Simulation of Liquids, Clarendon Press, Oxford, 1987.

[13] Frenkel, D.; Smit, B. Understanding Molecular Simulations: From Algorithms to Applications, Academic Press, San Diego, CA, 1996.

[14] Nosé, S. Mol. Phys. 1984, 52, 255.

[15] Hoover, W. G. Phys. Rev. 1985, A31, 1695.

[16] Andersen, H. C. J. Chem. Phys. 1980, 72, 2384.

[17] De Leeuw, S. W.; Perram, J. W.; Smith, E. R. Proc. R. Soc. London 1980, A373, 27.

[18] Darden, T. A.; York, D. M.; Pedersen, L. G. J. Chem. Phys. 1993, 98, 10089.

[19] Toukmaji, A. Y.; Board Jr., J. A. Comput. Phys. Commun. 1996, 95, 73.

[20] Tuckerman, M. E.; Berne, B. J.; Martyna, G. J. J. Phys. Chem. B 1992, 97, 1990.

[21] Izaguirre, J. A.; Reich, S.; Skeel, R. D. J. Chem. Phys. 1999, 110, 9853

[22] Ryckaert, J.; Ciccotti, G.; Berendsen, H. J. C. J. Comput. Phys. 1977, 23, 327.

[23] Andersen, H. C. J. Comput. Phys. 1983, 52, 24.

[24] Miyamoto, S.; Kollman, P. A. J. Comput. Chem. 1992, 13, 952.

[25] Brown, D.; Clarke, J. H. R.; Okuda, M.; Yamazaki, T. Comput. Phys. Commun. 1993, 74, 67.

[26] Chipot, C.; ángyán, J. G. New J. Chem. 2005, 29, 411.

[27] Sagui, C.; Pedersen, L. G.; Darden, T. A. J. Chem. Phys. 2004, 120, 73.

[28] Engle, R. D.; Skeel, R. D.; Drees, M. J. Comput. Phys. 2005, 206, 432.

[29] Grubmüller, H.; Heller, H.; Schulten, K. MC–Computermagazin 1988, 11, 48.

[30] Heller, H.; Grubmüller, H.; Schulten, K. Mol. Simul. 1990, 5, 133.

[31] Couturier, R.; Chipot, C. Comput. Phys. Commun. 2000, 124, 49.

[32] Bhandarkar, M.; Kalé, L. V.; de Sturler, E.; Hoeflinger, J. In Computational Science – ICCS 200, Proceedings part 2, Eds.: Alexandrov, V. N.; Dongarra, J. J.; Juliano, B. A.; Renner, R. S.; Tan, C. J. K., vol. 2074, 2001, pp. 108～117.

[33] Phillips, J. C.; Braun, R.; Wang, W.; Gumbart, J.; Tajkhorshid, E.; Villa, E.; Chipot, C.; Skeel, L.; Schulten, K. J. Comput. Chem. 2005, 26, 1781.

[34] Plimpton, S. J. Comput. Phys. 1995, 117, 1.

[35] Bowers, K. J.; Chow, E.; Xu, Huafeng; Dror, R. O.; Eastwood, M. P.; Gregersen, B. A.; Klepeis, J. L.; Kolossvary, I.; Moraes, M. A.; Sacerdoti, F. D.; Salmon, J. K.; Shan, Y. B.; Shaw, D. E. In Proceedings of the 2006 ACM/IEEE Conference on Supercomputing, 2006.

[36] Hess, B.; Kutzner, C.; van der Spoel, D.; Lindahl, E. J. Chem. Theor. Comput. 2008, 4, 435.

[37] Javadi, B.; Kondo, D.; Vincent, J. M.; Anderson, D. P. IEEE Transactions on Parallel and Distributed Systems 2011, 22, 1896.

[38] Richards, W. G. Nature Rev. Drug Discov. 2002, 1, 551.

[39] Shirts, M.; Pande, V. Science 2000, 290, 1903.

[40] Markoff, J. The New York Times 2003.

[41] Stone, J. E.; Phillips, J. C.; Freddolino, P. L.; Hardy, D. J.; Trabuco, L. G.; Schulten, K. J. Comput. Chem. 2007, 28, 2618.

[42] Anderson, J. A.; Lorenz, C. D.; Travesset, A. J. Comp. Phys. 2008, 227,5342.

[43] Shaw, D. E.; Deneroff, M. M.; Dror, R. O.; Kuskin, J. S.; Larson, R. H.; Salmon, J. K.; Young, C.; Batson, B.; Bowers, K. J.; Chao, J. C.; Eastwood, M. P.; Gagliardo, J.; Grossman, J. P.; Ho, C. R.; Ierardi, D. J.; Kolossváry, I.; Klepeis, J. L.; Layman, T.; McLeavey, C.; Moraes, M. A.; Mueller, R.; Priest, E. C.; Shan, Y.; Spengler, J.; Theobald, M.; Towles, B.; Wang, S. C. SIGARCH Comput. Archit. News 2007, 35, 1.

[44] Shaw, D. E.; Maragakis, P.; Lindorff-Larsen, K.; Piana, S.; Dror, R. O.; Eastwood, M. P.; Bank, J. A.; Jumper, J. M.; Salmon, J. K.; Shan, Y.; Wriggers, W. Science 2010, 330, 341.

[45] Dror, R. O.; Arlow, D. H.; Maragakis, P.; Mildorf, T. J.; Pan, A. C.; Xu, H.; Borhani, D. W.; Shaw, D. E. Proc. Natl. Acad. Sci. U. S. A. 2011, 108, 18684.

[46] Wriggers, W.; Stafford, K. A.; Shan, Y.B.; Piana, S.; Maragakis, P.; Lindorff-Larsen, K.; Miller, P. J.; Gullingsrud, J.; Rendleman, C. A.; Eastwood, M. P.; Dror, R. O.; Shaw, D. E. J. Chem. Theor. Comput. 2009, 5, 2595.

[47] Freddolino, P. L.; Harrison, C. B.; Liu, Y.; Schulten, K. Nature Phys. 2010, 6, 751.

[48] Gumbart, J.; Trabuco, L. G.; Schreiner, E.; Villa, E.; Schulten, K. Structure 2009, 17, 1453.

[49] Arkhipov, A.; Freddolino, P. L.; Schulten, K. Structure 2006, 14, 1767.

[50] 2012, The simulation of the AIDS virus capsid, representing about 12.5 million atoms, is one of the six projects selected for the launch of the petascale supercomputer Blue Waters, which harbors over 380,000 cores.

[51] Mei, C.; Sun, Y.; Zheng, G.; Bohm, E. J.; Kalé, L. V.; Phillips, J. C.; Harrison, C. In Proceedings of the 2011 ACM/IEEE Conference on Supercomputing, 2011, p. 12.

[52] Bowman, G. R.; Voelz, V. A.; Pande, V. S. J. Am. Chem. Soc. 2011, 133, 664.

[53] Liu, Y.; Strümpfer, J.; Freddolino, P. L.; Gruebele, M.; Schulten, K. J. Phys. Chem. Lett. 2012, 3, 1117.

[54] Lindorff-Larsen, K.; Piana, S.; Dror, R. O.; Shaw, D. E. Science 2011, 334, 517.

[55] Duan, Y.; Kollman, P. A. Science 1998, 282, 740.

[56] Freddolino, P. L.; Schulten, K. Biophys. J. 2009, 97, 2338.

[57] Rajan, A.; Freddolino, P. L.; Schulten, K. PLoS One 2010, 5, e9890.

[58] Bowman, G. R.; Pande, V. S. Proc. Natl. Acad. Sci. U. S. A. 2010, 107, 10890.

[59] Beauchamp, K. A.; Ensign, D. L.; Das, R.; Pande, V. S. Proc. Natl. Acad. Sci. U. S. A. 2011, 108, 12734.

[60] Freddolino, P. L.; Liu, F.; Gruebele, M.; Schulten, K. Biophys. J. 2008, 94, L75.

[61] Ensign, D. L.; Pande, V. S. Biophys. J. 2009, 96, L53.

[62] Lane, T. J.; Bowman, G. R.; Beauchamp, K.; Voelz, V. A.; Pande, V. S. J. Am. Chem. Soc. 2011, 133, 18413.

[63] Freddolino, P. L.; Park, S.; Roux, B.; Schulten, K. Biophys. J. 2009, 96, 3772.

[64] Lindorff-Larsen, K.; Piana, S.; Palmo, K.; Maragakis, P.; Klepeis, J. L.; Dror, R. O.; Shaw, D. E. Proteins: Struct. Funct. Bioinfo. 2010, 78, 1950.

[65] Kollman, P.; Dixon, R.; Cornell, W.; Fox, T.; Chipot, C.; Pohorille, A. In Computer Simulation of Biomolecular Systems: Theoretical and Experimental Applications, Eds.: Van Gunsteren, W. F.; Weiner, P. K., Escom, The Netherlands, 1997, p. 83.

[66] Le, L.; Lee, E. H.; Hardy, D. J.; Truong, T. N.; Schulten, K. PLoS Comput. Biol. 2010, 6.

[67] Wang, Y.; Tajkhorshid, E. Proc. Natl. Acad. Sci. U. S. A. 2008, 105, 9598.

[68] Dehez, F.; Pebay-Peyroula, E.; Chipot, C. J. Am. Chem. Soc. 2008, 130, 12725.

[69] Krammer, E. M.; Ravaud, S.; Dehez, F.; Frelet-Barrand, A.; Pebay-Peyroula, E.; Chipot, C. Biophys. J. 2009, 97, L25.

[70] Ravaud, S.; Bidon-Chanal, A.; Blesneac, I.; Machillot, P.; Juillan- Binard, C.; Dehez, F.; Chipot, C.; Pebay-Peyroula, E. ACS Chem. Biol. 2012, 7, 1164.

[71] Jensen, M. ?.; Jogini, V.; Borhani, D. W.; Leffler, A. E.; Dror, R. O.; Shaw, D. E. Science 2012, 336, 229.

[72] Nury, H.; Poitevin, F.; Van Renterghem, C.; Changeux, J. P.; Corringer, P. J.; Delarue, M.; Baaden, M. Proc. Natl. Acad. Sci. U. S. A. 2010, 107, 6275.

[73] Dror, R. O.; Pan, A. C.; Arlow, D. H.; Borhani, D. W.; Maragakis, P.; Shan, Y.; Xu, H.; Shaw, D. E. Proc. Natl. Acad. Sci. U. S. A. 2011, 108, 13118.

[74] Buch, I.; Giorgino, T.; Fabritiis, G. Proc. Natl. Acad. Sci. U. S. A. 2011, 108, 10184.

[75] Eds.: Chipot, C.; Pohorille, A., Free Energy Calculations. Theory and Applications in Chemistry and Biology, Springer Verlag, 2007.

[76] Hénin, J.; Forin, G.; Chipot, C.; Klein, M. L. J. Chem. Theor. Comput. 2010, 6, 35.

[77] Lelièvre, T.; Stoltz, G.; Rousset, M., Free Energy Computations: A Mathematical Perspective, Imperial College Press, London, 2010.

[78] Sugita, Y.; Okamoto, Y. Chem. Phys. Lett. 1999, 314, 141.

[79] Sugita, Y.; Kitao, A.; Okamoto, Y. J. Chem. Phys. 2000, 113, 6042.

[80] Fukunishi, H.; Watanabe, O.; Takada, S. J. Chem. Phys. 2002, 116, 9058.

[81] Dellago, C.; Bolhuis, P. G.; Csajka, F. S.; Chandler, D. J. Chem. Phys. 1998, 108, 1964.

[82] Weinan, E.; Ren, W. Q.; Vanden-Eijnden, E. Phys. Rev. B 2002, 66, 052301.

[83] Maragliano, L.; Vanden-Eijnden, E. Chem. Phys. Lett. 2006, 426, 168.

[84] Faradjian, A. K.; Elber, R. J. Chem. Phys. 2004, 120, 10880.

[85] Bolhuis, P. G.; Chandler, D.; Dellago, C.; Geissler, P. Ann. Rev. Phys. Chem. 2002, 59, 291.

[86] Torrie, G. M.; Valleau, J. P. J. Chem. Phys. 1977, 66, 1402.

[87] Roux, B. Comput. Phys. Commun. 1995, 91, 275.

[88] Huber, T.; Torda, A. E.; van Gunsteren, W. F. J. Comput. Aided Mol. Des. 1994, 8, 695.

[89] Grubmüller, H. Phys. Rev. E 1995, 52, 2893.

[90] Laio, A.; Parrinello, M. Proc. Natl. Acad. Sci. U. S. A. 2002, 99, 12562.

[91] Darve, E.; Pohorille, A. J. Chem. Phys. 2001, 115, 9169.

[92] Hénin, J.; Chipot, C. J. Chem. Phys. 2004, 121, 2904.

[93] Carter, E.; Ciccotti, G.; Hynes, J. T.; Kapral, R. Chem. Phys. Lett. 1989, 156, 472.

[94] Rosso, L.; Tuckerman, M. E. Mol. Simul. 2002, 28, 91.

[95] Chipot, C.; Lelièvre, T. SIAM J. Appl. Math. 2011, 71, 1673.

[96] Minoukadeh, K.; Chipot, C.; Lelièvre, T. J. Chem. Theor. Comput. 2010, 6, 1008.

[97] Brooks, B. R.; Brooks, C. L.; Mackerell, A. D.; Nilsson, L.; Petrella, R. J.; Roux, B.; Won, Y.; Archontis, G.; Bartels, C.; Boresch, S.; Caflisch, A.; Caves, L.; Cui, Q.; Dinner, A. R.; Feig, M.; Fischer, S.; Gao, J.; Hodoscek, M.; Im, W.; Kuczera, K.; Lazaridis, T.; Ma, J.; Ovchinnikov, V.; Paci, E.; Pastor, R. W.; Post, C. B.; Pu, J. Z.; Schaefer, M.; Tidor, B.; Venable, R. M.; Woodcock, H. L.; Wu, X.; Yang, W.; York, D. M.; Karplus, M. J. Comput. Chem. 2009, 30, 1545.

[98] Jarzynski, C. Phys. Rev. Lett. 1997, 78, 2690.

[99] Crooks, G. E. Phys. Rev. E 1999, 60, 2721.

[100] Jensen, M. ?.; Park, S.; Tajkhorshid, E.; Schulten, K. Proc. Natl. Acad. Sci. U. S. A. 2002, 99, 6731.

[101] Fu, D.; Libson, A.; Miercke, L. J.; Weitzman, C.; Nollert, P.; Krucinski, J.; Stroud, R. M. Science 2000, 290, 481.

[102] Hénin, J.; Tajkhorshid, E.; Schulten, K.; Chipot, C. Biophys. J. 2008, 94, 832.

[103] Bernèche, S.; Roux, B. Nature 2001, 414, 73.

[104] Doyle, D. A.; Cabral, J. M.; Pfuetzner, R. A.; Kuo, A. L.; Gulbis, J. M.; Cohen, S. L.; Chait, B. T.; MacKinnon, R. Science 1998, 280, 69.

[105] Gumbart, J. C.; Chipot, C.; Schulten, K. J. Am. Chem. Soc. 2011, 133, 7602.

[106] Gumbart, J. C.; Chipot, C.; Schulten, K. Proc. Natl. Acad. Sci. U. S. A. 2011, 108, 3596.

[107] Dorairaj, S.; Allen, T. W. Proc. Natl. Acad. Sci. U. S. A. 2007, 104, 4943.

[108] Hessa, T.; Kim, H.; Bihlmaier, K.; Lundin, C.; Boekel, J.; Andersson, H.; Nilsson, I.; White, S. H.; von Heijne, G. Nature 2005, 433, 377.

[109] Trabuco, L. G.; Villa, E.; Mitra, K.; Frank, J.; Schulten, K. Structure 2008, 16, 673.

[110] Trabuco, L. G.; Villa, E.; Schreiner, E.; Harrison, C. B.; Schulten, K. Methods 2009, 49, 174.

[111] McCammon, J. A.; Gelin, B. R.; Karplus, M. Nature 1977, 267, 585.

[112] Schulten, K.; Phillips, J. C.; Kalé, L. V.; Bhatele, A. In Petascale Computing: Algorithms and Applications, Ed.: Bader, D., Chapman and Hall/CRC Press, Taylor and Francis Group, New York, 2008, p. 165.

[113] van Gunsteren, W. F.; Bakowies, D.; Baron, R.; Chandrasekhar, I.; Christen, M.; Daura, X.; Gee, P.; Geerke, D. P.; Gl?ttli, A.; Hünenberger, P. H.; Kastenholz, M. A.; Oostenbrink, C.; Schenk, M.; Trzesniak, D.; van der Vegt, N. F. A.; Yu, H. B. Angew. Chem., Int. Ed. Engl. 2006, 45, 4064.

[114] Karplus, M. Annu. Rev. Biophys. Biomol. Struct. 2006, 35, 1.

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