Structure Prediction of Helical Transmembrane Proteins at Two Length Scales

As the first step toward a multi-scale, hierarchical computational approach for membrane protein structure prediction, the packing of transmembrane helices was modeled at the residue and atom levels, respectively. For predictions at the residue level, the helix-helix and helix-membrane interactions were described by a set of knowledge-based energy functions. For predictions at the atom level, CHARMM19 force field was used. To facilitate the system to overcome energy barriers, the Wang-Landau method was employed, where a random walk is performed in the energy space with a uniform probability. Native-like structures were predicted at both levels for two model systems, each of which consists of two transmembrane helices. Interestingly, consistent results were obtained from simulations at the residue and atom levels for the same system, strongly suggesting the feasibility of a hierarchical approach for membrane protein structure predictions.

[1]  Yaoqi Zhou,et al.  Web-based toolkits for topology prediction of transmembrane helical proteins, fold recognition, structure and binding scoring, folding-kinetics analysis and comparative analysis of domain combinations , 2005, Nucleic Acids Res..

[2]  K G Fleming,et al.  Riding the wave: structural and energetic principles of helical membrane proteins. , 2000, Current opinion in biotechnology.

[3]  Y. Okamoto,et al.  Prediction of membrane protein structures by replica-exchange Monte Carlo simulations: case of two helices. , 2004, The Journal of chemical physics.

[4]  M. Karplus,et al.  Collective motions in proteins: A covariance analysis of atomic fluctuations in molecular dynamics and normal mode simulations , 1991, Proteins.

[5]  Jaume Torres,et al.  Contribution of energy values to the analysis of global searching molecular dynamics simulations of transmembrane helical bundles. , 2002, Biophysical journal.

[6]  A. Krogh,et al.  A combined transmembrane topology and signal peptide prediction method. , 2004, Journal of molecular biology.

[7]  A. Kernytsky,et al.  Transmembrane helix predictions revisited , 2002, Protein science : a publication of the Protein Society.

[8]  D. Engelman,et al.  Specificity and promiscuity in membrane helix interactions , 1994, Quarterly Reviews of Biophysics.

[9]  D. T. Jones,et al.  Folding in lipid membranes (FILM): A novel method for the prediction of small membrane protein 3D structures , 2003, Proteins.

[10]  D. Landau,et al.  Determining the density of states for classical statistical models: a random walk algorithm to produce a flat histogram. , 2001, Physical review. E, Statistical, nonlinear, and soft matter physics.

[11]  D C Rees,et al.  Forces involved in the assembly and stabilization of membrane proteins 1 , 1992, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[12]  D. Engelman,et al.  Membrane protein folding and oligomerization: the two-stage model. , 1990, Biochemistry.

[13]  D. Engelman,et al.  Computation and mutagenesis suggest a right‐handed structure for the synaptobrevin transmembrane dimer , 2001, Proteins.

[14]  Hongyi Zhou,et al.  Distance‐scaled, finite ideal‐gas reference state improves structure‐derived potentials of mean force for structure selection and stability prediction , 2002, Protein science : a publication of the Protein Society.

[15]  M. Karplus,et al.  Simulation of activation free energies in molecular systems , 1996 .

[16]  J M Sturtevant,et al.  Thermodynamic measurements of the contributions of helix-connecting loops and of retinal to the stability of bacteriorhodopsin. , 1992, Biochemistry.

[17]  J R Banavar,et al.  Deciphering the folding kinetics of transmembrane helical proteins. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[18]  T. N. Bhat,et al.  The Protein Data Bank , 2000, Nucleic Acids Res..

[19]  Garland R. Marshall,et al.  A potential smoothing algorithm accurately predicts transmembrane helix packing , 1999, Nature Structural Biology.

[20]  C Menzel,et al.  Protein, lipid and water organization in bacteriorhodopsin crystals: a molecular view of the purple membrane at 1.9 A resolution. , 1999, Structure.

[21]  D. Engelman,et al.  Improved prediction for the structure of the dimeric transmembrane domain of glycophorin A obtained through global searching , 1996, Proteins.

[22]  Y. Okamoto,et al.  Self-assembly of transmembrane helices of bacteriorhodopsin by a replica-exchange Monte Carlo simulation , 2004 .

[23]  James H. Prestegard,et al.  A Transmembrane Helix Dimer: Structure and Implications , 1997, Science.

[24]  G. Heijne,et al.  Membrane proteins: from sequence to structure. , 1994, Annual review of biophysics and biomolecular structure.

[25]  C-C Chen,et al.  Computer simulations of membrane protein folding: structure and dynamics. , 2003, Biophysical journal.

[26]  H. Scheraga,et al.  On the multiple-minima problem in the conformational analysis of molecules: deformation of the potential energy hypersurface by the diffusion equation method , 1989 .

[27]  Peter L. Freddolino,et al.  Prediction of structure and function of G protein-coupled receptors , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[28]  D. Landau,et al.  Efficient, multiple-range random walk algorithm to calculate the density of states. , 2000, Physical review letters.

[29]  J U Bowie,et al.  Helix packing in membrane proteins. , 1997, Journal of molecular biology.

[30]  G R Marshall,et al.  Novel approach to computer modeling of seven-helical transmembrane proteins: current progress in the test case of bacteriorhodopsin. , 2001, Acta biochimica Polonica.

[31]  James U Bowie,et al.  A simple method for modeling transmembrane helix oligomers. , 2003, Journal of molecular biology.

[32]  Hongyi Zhou,et al.  An accurate, residue‐level, pair potential of mean force for folding and binding based on the distance‐scaled, ideal‐gas reference state , 2004, Protein science : a publication of the Protein Society.

[33]  J. Pablo,et al.  Density of states simulations of proteins , 2003 .

[34]  G. Heijne,et al.  Genome‐wide analysis of integral membrane proteins from eubacterial, archaean, and eukaryotic organisms , 1998, Protein science : a publication of the Protein Society.

[35]  D. Engelman,et al.  Intramembrane helix-helix association in oligomerization and transmembrane signaling. , 1992, Annual review of biophysics and biomolecular structure.

[36]  Ying Xu,et al.  Energetics and stability of transmembrane helix packing: A replica‐exchange simulation with a knowledge‐based membrane potential , 2006, Proteins.

[37]  G. Heijne.  The distribution of positively charged residues in bacterial inner membrane proteins correlates with the trans‐membrane topology , 1986, The EMBO journal.

[38]  S. White,et al.  Membrane protein folding and stability: physical principles. , 1999, Annual review of biophysics and biomolecular structure.

[39]  Yaoqi Zhou,et al.  Predicting the topology of transmembrane helical proteins using mean burial propensity and a hidden-Markov-model-based method , 2003 .