Simulations of Protein Folding

J. Kostrowicki and H.A. Scheraga, Application of the diffusion equation method for global optimization to oligopeptides, J. Phys. Chem. 96 (1992), 7442-7449. M. Levitt, A simplified representation of protein confomations for rapid simulation of protein folding, J. Mol. Biol. 104 (1976), 59-107. 

M. Levitt and A. Warshel, Computer simulation of protein folding. Nature 253 (1975), 694-698. 

Levitt M 1976. A Simplified Representation of Protein Conformations for Rapid Simulation of Protein Folding. Journal of Molecular Biology 104 59-107. 

M Levitt. A simplified representation of protein conformations for rapid simulation of protein folding. J Mol Biol 104 59-107, 1976. 

This distribution resembies the data cioseiy for rotamer (3, 3, 3) but also forms a very reasonable distribution when there are only seven data points (3, 3, 1). A good posterior predictive distribution for any protein structural feature can be used in simulations of protein folding or strucmre prediction. 

A Kolinski, J Skolmck. Monte Carlo simulations of protein folding. I. Lattice model and interaction scheme. Pi-otem 18 338-352, 1994. 

Gsponer J, Caflisch A. Molecular dynamics simulations of protein folding from the transition state. Proc Natl Acad Sci USA 2002 99 6719-24. 

Beck DAC, Daggett V. Methods for molecular dynamics simulations of protein folding/unfolding in solution. Methods 2004 34 112-20. 

Nymeyer H, Gnanakaran S, Garcfa AE (2004) Atomic simulations of protein folding using the replica exchange algorithm. Methods Enzymol 383 119-149. 

Daidone, I., Amadei, A., Roccatano, D., Nola, A. D., Molecular dynamics simulation of protein folding by essential dynamics sampling folding landscape of horse heart cytochrome c, Biophys. J. 2003, 85, 2865-2871... 

How well has Dill s prediction held up In 2000, the first ever microsecond-long molecular dynamics simulation of protein folding was reported. It required 750,000 node hours (equal to the product of the number of hours times the number of processors) of computer time on a Cray T3 supercomputer. According to Dill s prediction, this length of simulation was not to be expected until around 2010. However, as noted above, Dill s analysis does not take into account large-scale parallelization—which, unless the computation is communications-limited, will effectively increase the speed of a computation in proportion to the number of processors available. 

Liwo A, Khalili M, Scheraga HA (2005) Ab initio simulations of protein-folding pathways by molecular dynamics with the united-residue model of polypeptide chains. Proc. Natl. Acad. Sci. 

Standard molecular mechanics (MM) force fields have been developed that provide a good description of protein structure and dynamics,21 but they cannot be used to model chemical reactions. Molecular dynamics simulations are very important in simulations of protein folding and unfolding,22 an area in which they complement experiments and aid in interpretation of experimental data.23 Molecular dynamics simulations are also important in drug design applications,24 and particularly in studies of protein conformational changes,25,26 simulations of the structure and function of ion channels and other membrane proteins,27-29 and in studies of biological macromolecular assemblies such as F-l-ATPase.30... 

P. Eastman, N. Gronbech-Jensen, S. Doniach (2001) Simulation of protein folding by reaction path annealing. J. Chem. Phys. 114, pp. 3823-3841... 

Joan-Emma Shea, Miriam Friedel and Andrij Baumketner, Simulations of Protein Folding. 

Kolinski, A. and Skolnick, J., Monte Carlo simulations of protein folding. 11. Application to protein A, ROP, and crambin. Proteins, 18, 353, 1994. 

This technique holds promise for addressing the holy grail of molecular dynamics calculations - the simulation of protein folding over long time scales - by using wavelets to perform the dynamical calculation itself without having necessarily to focus on fine-scale details. 

Gsponer, J., Caflisch, A. Molecular dynamics simulations of protein folding from the transition state. In Fersth, A. (ed.) Proceedings of the National Academy of Sciences (PNAS), vol. 99, pp. 6719-6724. Washington (2002)... 

---