Michael Levitt's Annotated Publications (June 2001)
Thirty-three of his papers have been cited over 100 times (marked *) and twenty-two of these have been cited over 200 times (marked **); he is first author on nineteen of these papers. A paper he considers to be one of his twenty best is marked [a] and one of his ten best is marked [a+].
Protein Folding: Analysis and Methods
Analysis of Protein Structures
Six papers pioneered the description and explanation of structural patterns in proteins as deduced from the twenty or so structures known by 1975. These principles have endured and form the basis of our current understanding of protein architecture. The latest paper is an attempt to be objective, leading to the discovery that is it impossible!
(12**) Levitt, M. and C. Chothia. Structural Patterns in Globular Proteins. Nature 261, 552-558 (1976). [a+]
First definition of protein fold classes.
(14**) Levitt, M. and J. Greer. Automatic Identification of Secondary Structure in Globular Proteins. J. Mol. Biol. 114, 181-239 (1977). [a]
First automatic identification of protein secondary structure from the atomic coordinates.
(15**) Chothia, C., M. Levitt and D. Richardson. Structure of Proteins: Packing of a-Helices and Pleated Sheets. Proc. Nat. Acad. Sci. USA 74, 4130-4134 (1977).
First explanation of secondary structure packing motifs.
(21**) Levitt, M. Conformational Preferences of Amino Acids in Globular Proteins. Biochemistry 17, 4277-4285 (1978).
Amino acid preferences for secondary structure shown to make stereochemical sense.
(22**) Janin, J., S. Wodak, M. Levitt and B. Maigret. The Conformation of Amino Acid Side Chains in Proteins. J. Mol. Biol. 125, 357-386 (1978).
First analysis of side-chain conformations show preferred states.
(27**) Chothia, C., M. Levitt and D. Richardson. Helix to Helix Packing in Proteins. J. Mol. Biol. 145, 215-250 (1981).
(90) Levitt, M. Competitive Assessment of Protein Fold Recognition and Alignment Accuracy. Proteins, Struct., Funct. and Gen. Suppl, 1, 92-104 (1997).
Assessment of the CASP2 threading results was surprisingly difficult: we are always subjective to a greater or lesser degree.
Potential Energy Functions
Five papers have described all-atom potential energy functions designed for reliable yet efficient simulation of biomolecules in solution. By focusing on simple functional forms with few parameters determined by calibration, he has been able to elucidate physical principles and write efficient programs.
(3) Warshel, A., M. Levitt and S. Lifson. Consistent Force Field for Calculation of Vibrational Spectra and Conformations of Some Amides and Lactam Rings. J. Mol. Spect. 33, 84-98 (1970)
(24) Lifson, S. and M. Levitt. On Obtaining Energy Parameters from Crystal Structure Data. Computers and Chemistry 3, 49-51 (1979).
(44**) Levitt, M. and M. F. Perutz. Aromatic Rings Act as Hydrogen Bond Acceptors. J. Mol. Biol. 201, 751-754 (1988). [a]
Simple electrostatics explains aromatic hydrogen bonds.
(72) Levitt, M., M. Hirshberg, R. Sharon and V. Daggett. Potential Energy Function and Parameters for Simulations of the Molecular Dynamics of Proteins and Nucleic Acids in Solution. Computer Physics Communications, 91, 215-231 (1995).
Description of the ENCAD potential with emphasis on smooth truncation.
(83) Levitt, M., Hirshberg, M., Sharon, R., Laidig, K.E., and Daggett, V. Calibration and Testing of a Water Model for Simulation of the Molecular Dynamics of Proteins and Nucleic Acids in Solution. J. Phys. Chem., B25, 5051-5061 (1997).
A simple flexible three-point water model works well for pure water, simple solutions and macromolecules in water.
(111). Xia. Y. and M. Levitt. Extracting Knowledge-Based Energy Functions from Protein Structures by Error Rate Minimization: Comparison of Methods Using Lattice Model. J. Chem. Phys. 113, 9318-9330 (2000).
A novel method for deducing energy parameters from protein structures is expected to have wide-ranging applications.
Three papers show how minimization of a macromolecular energy function can be used to refine protein coordinates. By using an all-atom potential energy function and Cartesian coordinates, this formed the basis for subsequent molecular dynamics simulations. In collaboration with Jack, this also led to the popular Jack-Levitt or EREF method for refining directly against x-ray intensities. This method, in turn, formed the basis for Brünger's program X-Plor, used for all present-day refinement of X-ray and NMR structures.
(1**) Levitt, M. and S. Lifson. Refinement of Protein Conformations Using a Macromolecular Energy Minimization Procedure. J. Mol. Biol. 46, 269-279 (1969). [a]
First energy minimization of an entire protein molecule.
(6**) Levitt, M. Energy Refinement of Hen Egg-White Lysozyme. J. Mol. Biol. 82, 393-420 (1974).
First use of minimization to refine X-ray coordinates in conjunction with Diamond's Real-Space refinement.
(19**) Jack, A. and M. Levitt. Refinement of Large Structures by Simultaneous Minimization of Energy and R Factor. Acta Crystallogr. A34, 931-935 (1978). [a]
First use of R-factor as a pseudo-energy term in a refinement method popular for a decade.
Molecular Dynamics Simulations
Fifteen papers have improved methods for generating and analyzing molecular dynamics trajectories. Emphasizing the need to remain close to the native structure, new protocols have been devised for realistic simulation of macromolecular dynamics in solution. Normal mode dynamics was applied to four proteins and showed the importance of low-frequency collective motion.
(28) Levitt, M. The Molecular Dynamics of Hydrogen Bonds in Bovine Pancreatic Trypsin Inhibitor Protein. Nature 294, 379-380 (1981).
(29) Levitt, M. Hydrogen Bond and Internal Solvent Dynamics of BPTI Protein. Ann. NY Acad. Sci. 367, 162-181 (1981).
(31*) Levitt, M. Protein Conformation, Dynamics and Folding by Computer Simulation. Ann. Rev. Biophys. Bioeng. 11, 251-271 (1982).
(33**) Levitt, M. Molecular Dynamics of Native Protein: I. Computer Simulation of Trajectories. J. Mol. Biol. 168, 595-620 (1983). [a+]
Show how molecular dynamics can keep the structure close to the starting X-ray structure.
(34*) Levitt, M. Molecular Dynamics of Native Protein: II. Analysis and Nature of Motion. J. Mol. Biol. 168, 595-620 (1983).
Use new analysis methods to describe how proteins move.
(38*) Levitt, M., C. Sander and P. S Stern. Protein Normal-Mode Dynamics: Trypsin Inhibitor, Crambin, Ribonuclease and Lysozyme. J. Mol. Biol. 181, 423-447 (1985). [a]
Use normal modes in torsional space for protein dynamics.
(45**) Levitt, M. and R. Sharon. Accurate Simulation of Protein Dynamics in Solution. Proc. Natl. Acad. Sci. USA. 85, 7557-7561 (1988). [a+]
First realistic simulation of protein dynamics in water.
(47) Levitt, M. Molecular Dynamics of Macromolecules in Water. Chemica Scripta, 29A, 197-203 (1989).
(55) Levitt, M. Real-Time Interactive Frequency Filtering of Molecular Dynamics Trajectories. J. Mol. Biol. 220, 1-4 (1991).
(57) Daggett, V. and M. Levitt. A Molecular Dynamics Simulation of the C-Terminal Fragment of the L7/L12 Ribosomal Protein in Solution. Chemical Phys. 158, 501-512 (1991).
(67) Levitt, M. and B. Park. Water: Now You See It, Now You Don't. Structure. 1 223-226 (1993).
(74) Gerstein, M., J. Tsai and M. Levitt. The Volume of Atoms on the Protein Surface: Calculated from Simulation using Voronoi Polyhedra. J. Mol. Biol., 249, 955-966 (1995).
Water has a lower density near nonpolar surfaces.
(77) Tsai, J., M. Gerstein and M. Levitt. Keeping the Shape but Changing the Charge: A Simulation Study of Urea and Its Iso-Steric Analogues. J. Chem. Phys., 104, 9417-9430 (1996).
Urea is shown to have little effect on the structure of water.
(78) Huang, E.S., J. Tsai, S. Subbiah and M. Levitt. Using a Hydrophobic Contact Potential to Evaluate Native and Near-Native Folds Generated by Molecular Dynamics Simulations. J. Mol. Biol., 257, 716-725(1996).
(88) Tsai, J., M. Gerstein, and M. Levitt. Simulating the Minimum Core for Hydrophobic Collapse in Globular Proteins. Protein Science, 6, 1-11 (1997).
Simulations of simple solutions reveal that the hydrophobic effect is cooperative and that proteins need to be large enough to have a stable core.
(92) Gerstein, M. and M. Levitt. Simulating Water and the Molecules of Life. Scientific American, Nov 101-105 (1998).
(114). Raschke, T.M., Tsai, J. and M. Levitt. Quantification of the Hydrophobic Interaction by Simulations of the Aggregation of Small Hydrophobic Solutes in Water. Proc. Natl. Acad. Sci., 98, 5965-5660 (2001).
We are able to simulate hydrophobic clustering using simple all-atom potentials with explicit water.
Simplified Representations for Folding
Four papers have introduced several new representations for polypeptide chains that can be used for rapid exploration of conformational space. The notion that the energy of a protein could be estimated from a simple string of beads continues to have many applications.
(11**) Levitt, M. A Simplified Representation of Protein Conformations for Rapid Simulation of Protein Folding. J. Mol. Biol. 104, 59-107 (1976). [a+]
Energy calculations can be done on simplified models.
(17) Levitt, M. Protein Folding as a Random Walk. Proceedings of the 7-th Taniguichi Symposium, 1977.
Random coils can be very compact and native-like.
(60*) Hinds, D. A. and M. Levitt. A Lattice Model for Protein Structure Prediction at Low Resolution. Proc. Natl. Acad. Sci. USA. 89, 2536-2540 (1992).
A very simple model for use in the first exhaustive search of folded conformations.
(73) Park, B. and M. Levitt. The Complexity and Accuracy of Discrete State Models of Protein Structure. J. Mol. Biol., 249, 493-507 (1995).
Best-fit RMS deviation depends on number of conformations per amino acid (complexity).
(112). Fain, B. and M. Levitt. A Novel Method for Sampling Alpha-helical Protein Backbones, J. Mol. Biol., 305, 191-201 (2001).
A novel method of helix assembly.
Simulating Protein Folding
Twelve papers have used simplified representations of polypeptide chains to fold proteins by energy minimization and exhaustive enumeration. The latest work shows conclusively that the native amino acid sequence distinguishes the native structure from millions of alternatives.
(9**) Levitt, M. and A. Warshel. Computer Simulation of Protein Folding. Nature 253, 694-698 (1975). [a+]
First folding of a simplified chain, using time-averaged forces to give a compact, partially ordered globule.
(13) Warshel, A. and M. Levitt. Folding and Stability of Helical Proteins: Carp Myogen. J. Mol. Biol. 106, 421-437 (1976).
(26) Levitt, M. Effect of Proline Residues on Protein Folding. J. Mol. Biol. 145, 251-263 (1981).
First classification of prolines into classes: Gly-Pro is specially permissive, Pro-Pro is specially restrictive.
(35*) Levitt, M. Protein Folding by Restrained Energy Minimization and Molecular Dynamics. J. Mol. Biol. 170, 723-764 (1983). [a+]
First use of energy minimization and annealing dynamics shows that even with restraints, non-native folds do occur. Formed basis for NMR structure determination methods.
(53) Levitt, M. Protein Folding. Curr. Opinions Struct. Biol. 1, 224-229 (1991).
(70) Hinds, D. A. and M. Levitt. Exploring Conformational Space with a Simple Lattice Model for Protein Structure. J. Mol. Biol. 243, 668-682 (1994). [a]
At low resolution native structure is distinguished from many alternatives by the native amino acid sequence.
(71) Hinds, D. A. and M. Levitt. Simulation of Protein-Folding Pathways: Lost in (Conformational) Space? Trends in Biotechnology. 13, 23-27 (1995).
(75) Huang, E.S., S. Subbiah and M. Levitt. Recognizing Native Folds by the Arrangement of Hydrophobic and Polar Residues. J. Mol. Biol., 252, 709-720 (1995).
A simple hydrophobic energy function is able to distinguish the native structure from threading decoys.
(79) Hinds, D.A. and M. Levitt. From Structure to Sequence and Back Again. J. Mol. Biol., 258, 201-209 (1996).
Sequence optimization is used on simple lattice folds to show that the native sequence is not optimally selective for the native structure.
(80) Park, B. and M. Levitt. Energy Functions that Discriminate X-ray and Near-Native Folds from Well-Constructed Decoys. J. Mol. Biol., 258, 367-392 (1996). [a+]
Predicting structure by discriminating finding folds that are native-like is shown to be a very powerful, general paradigm.
(82) Park, B., Huang, E. S. and M. Levitt. Factors Affecting The Ability of Energy Functions to Discriminate Correct from Incorrect Folds. J. Mol. Biol., 266, 831-846 (1997).
Widely used energy functions that seem sensible are not always able to discriminate the native-like fold in a large set of decoys
(85) Levitt, M., M. Gerstein, E.S. Huang, S. Subbiah and J. Tsai. Protein Folding: The End-Game. Ann. Rev. Biochemistry, 66, 549-579 (1997).
Contrary to popular belief, the hard step in protein folding is near the end of the procedure when the chain already looks native-like.
(98). Samudrala, R., Y. Xia, E.S. Huang, and M. Levitt. Bona Fide Ab Initio Protein Structure Prediction Using a Combined Hierarchical Approach. Proteins, Struct., Funct. and Gen. Suppl. 3S, 194-198 (1999).
The hierarchical approach pioneered in the group is shown to do well at ab initio prediction at CASP3.
(108). Xia, Y., Huang, E.S., Levitt, M. and Samudrala, R. Ab initio construction of protein tertiary structures using a hierarchical approach. J. Mol. Biol., 300, 171-185 (2000).
Simulating Protein Unfolding
Five papers have used molecular dynamics to simulate protein and peptide unfolding. He has concentrated on the qualitative aspects, emphasizing the nature of the intermediate conformations and transitions between them. This approach has now been adopted by others previously more interested in calculating free energies rather than describing structural details.
(59*) Daggett, V. and M. Levitt. Molecular Dynamics Simulation of Helix Denaturation. J. Mol. Biol. 223, 1121-1138 (1992).
Showing temperature dependence of a-helix melting.
(62) Daggett, V. and M. Levitt. Molecular Dynamics Simulation of the Molten Globule State. Proc. Natl. Acad. Sci. USA. 89, 5142-5146 (1992).
First simulation of protein unfolding. Intermediate is compact, has secondary structure, yet not well-ordered.
(65) Daggett, V. and M. Levitt. Realistic Simulation of Native Protein Dynamics in Solution and Beyond. Ann. Rev. Biophys & Biomol. Struct. 22, 353-380 (1993).
(66) Daggett, V. and M. Levitt. Protein Unfolding Pathways Explored Through Molecular Dynamics Simulations. J. Mol. Biol. 232, 600-618 (1993). [a+]
(68) Daggett, V. and M. Levitt. Protein Folding <-> Unfolding Dynamics. Current Opinions in Structural Biology 4, 291-295 (1994).
(99). Tsai, J., M. Levitt and D. Baker. Hierarchy of Structure Loss in MD Simulations of SRC SH3 Domain Unfolding. J. Mol. Biol. 291, 215-225 (1999).
Modelling Proteins: General
Five papers have concentrated on new methods for modeling protein structure and include collaborations with experimental groups that verified predictions (new SS bridges in T4 lysozyme and stabilizing ion binding sites in subtilisin).
(46) Levitt, M. A Calculated Conformation for the Folding Transition State of Bovine Pancreatic Trypsin Inhibitor. In Protein Structure and Protein Engineering, ed. Winnacker E. L. and Huber, R. Springer-Verlag, Berlin, Heidelberg pp. 45-50 (1988).
(49*) Matsumura, M., W. J. Becktel, M. Levitt and B. W. Matthews. Stabilization of Phage T4 Lysozyme by Engineered Disulfide Bonds. Proc. Natl. Acad. Sci. USA. 86, 6562-6566 (1989).
Prediction and experimental verification of SS-bridge mutants.
(54) Lee, C. and M. Levitt. Accurate Prediction of the Stability and Activity Effects of Site-directed Mutagenesis of a Protein Core. Nature, 352, 448-451 (1991).
Mutant structure and energetics correlate well with experiment. Controversial due to emphasis on sampling rather than potential energy function.
(58) Narhi, L. O., Y. Stabinsky, M. Levitt, L. Miller, R. Sachdev, S. Finley, S. Park, C. Kolvenbach, T. Arakawa and M. Zukowski. Enhanced stability of subtilisin by three point mutations. Biotechnology and Applied Biochemistry 1, 12-24 (1991).
Prediction and verification of mutants that stabilize a protein by introducing ion binding sites.
(61*) Levitt, M. Accurate Modelling of Protein Conformation by Automatic Segment Matching. J. Mol. Biol. 226, 507-533 (1992). [a]
Accurate and fully automatic method to build missing side and main-chain atoms with clear applications to homology modeling.
(94) Huang E.S., P. Koehl, M. Levitt, R.V. Pappu and J.W. Ponder. Accuracy of side-chain prediction upon near-native protein backbones generated by Ab initio folding methods. Proteins, 33, 204-217 (1998).
(107). Samudrala, R. Huang, E.S., Koehl, P. and M. Levitt. Constructing side chains on near-native main chains for ab initio protein structure prediction. Protein Eng. 3, 453-457 (2000).
Modelling Proteins: Antibodies
Nine papers, all in collaboration with experimentalists, showed that antibody variable loops could be modeled well by his fully automatic method and that these models were useful to experimentalists, particular those doing NMR.
(40*) Chothia, C., A. M. Lesk, M. Levitt, A. G. Amit, R. A. Mariuzza, S. E. V. Phillips and R. J. Poljak. The Predicted Structure of Immunoglobulin D1.3 and Its Comparison with the Crystal Structure. Science, 233, 755-758 (1986).
First modeling of antibody variable domains and comparison to x-ray structure.
(43) Anglister, J., M. Bond, T. Frey, D. Leahy, M. Levitt, H. M. McConnell and M. Whittaker. Contribution of Tryptophan Residues to the Combining Site of a Monoclonal Anti-Dinitrophenyl Spin-Label Antibody. Biochemistry, 26, 6058-6064 (1987).
(48) Levy, R., O. Assulin, T. Scherf, M. Levitt and J. Anglister. Probing Antibody Diversity by 2D NMR: Comparison of Amino Acid Sequences, Predicted Structures and Observed Antibody-Antigen Interactions in Complexes of Two Antipeptide Antibodies. Biochemistry, 28, 7168-7175 (1989).
(50**) Chothia, C., A. M. Lesk, M. Levitt, A. Tramontano, S. J. Smith-Gill, G. Air, S. Sheriff, E. A. Padlan, D. Davies, W. R. Tulip and P. M. Colman. The Conformations of Immunoglobulin Hypervariable Regions. Nature, 342, 877-883 (1989).
(51**) Queen, C., W. P. Schneider, H. E. Selick, P. W. Payne, N. F. Landolfi, J. F. Duncan, N. M. Avdalovic, M. Levitt, R. P. Junghans and T. A. Waldmann. A Humanized Antibody that Binds to the IL-2 Receptor. Proc. Natl. Acad. Sci. USA. 86, 10029-10033 (1989).
(52) Zilber, B., T. Scherf, M. Levitt and J. Anglister. NMR Derived Model for a Peptide-Antibody Complex. Biochemistry, 29, 10032-10041 (1990).
(56) Theriault, T. P, G. S. Rule, D. J. Leahy, M. Levitt and H. M. McConnell. Structural and Kinetic Studies of the Fab Fragment of a Monoclonal Anti-Spin Label Antibody by NMR. J. Mol. Biol. 221, 257-270 (1991).
(63) Scherf, T., R. Hiller, F. Naider, M. Levitt and Y. Anglister. Induced Peptide Conformations in Different Antibody Complexes: Molecular Modelling of the Three-Dimensional Structure of Peptide-Antibody Complexes Using NMR Distance Restraints. Biochemistry 31, 6884-6897 (1992).
(76) Shoham, S., T. Scherf, J. Anglister, M. Levitt, E. A. Merritt and W. G. J. Hol. Structural Diversity in a Conserved Cholera Toxin Epitope Involved in Ganglioside Binding. Protein Science, 4, 841-848 (1995).
Miscellaneous Methods and Applications
New methods were developed for rapid energy calculations for interactive molecular graphics and rapid solution of the Poisson-Boltzmann equation.
(39) Pattabiraman, N., M. Levitt, T. E. Ferrin and Langridge, R. Computer Graphics in Real Time Docking with Energy Calculations and Minimization, J. Comput. Chem. 6, 432-436 (1985).
(81) Zhou, Z., Payne, P., Vasquez, M., Kuhn, N. and M. Levitt. Finite-Difference Solution of the Poisson-Boltzmann Equation: Complete Elimination of Self-Energy. J. Comp. Chem.., 11, 1344-1351 (1996).
Reactions and Binding
Three papers on enzyme reactions and substrate binding all made pioneering observations. This study of mechanisms was not continued due to his desire to focus on structure and dynamics.
(7) Levitt, M. On the Nature of the Binding of Hexa-N-Acetyl Glucosamine Substrate to Lysozyme. In Peptides, Polypeptides and Proteins, Wiley, New York, pp. 99-113 (1974).
Importance of electrostatic rather than steric strain.
(10**) Warshel, A. and M. Levitt. Theoretical Studies of Enzymic Reactions: Dielectric, Electrostatic and Steric Stabilization of the Carbonium Ion in the Reaction of Lysozyme. J. Mol. Biol. 103, 227-249 (1976). [a+]
First combined quantum mechanics and molecular mechanics calculation of a reaction.
(37) Henry, E. R., M. Levitt and W. A. Eaton. Molecular Dynamics Simulation of Photodissociation of Carbon Monoxide from Hemoglobin. Proc. Natl. Acad. Sci. USA, 82, 2034-2038 (1985).
First use of molecular dynamics to simulate sub-picosecond processes observed experimentally.
Nucleic Acid Folding
Eight papers on RNA and DNA reflect long-term interests that have been given lower priority due to work on proteins. A number of these papers made seminal discoveries and had significant impact.
(2*) Levitt, M. Detailed Molecular Model for Transfer Ribonucleic Acid. Nature 224, 759-763 (1969). [a]
Model of tRNA was closest to x-ray structure.
(4) Levitt, M. Folding of Nucleic Acids. In Polymerization in Biological Systems, Ciba Foundation Symposium 7, Elsevier, Amsterdam, pp. 146-171 (1972).
(5) Levitt, M. Orientation of Double-Helical Segments in Crystals of Yeast Phenylalanine Transfer RNA. J. Mol. Biol. 80, 255-263 (1973).
(16**) Finch, J. T., L. C. Lutter, D. Rhodes, R. S. Brown, B. Rushton, M. Levitt and A. Klug. Structure of the Nucleosome Core Particles of Chromatin. Nature 269, 29-35 (1977).
(18**) Levitt, M. and A. Warshel. Extreme Conformational Flexibility of the Furanose Ring in DNA and RNA. J. Am. Chem. Soc. 100, 2607-2613 (1978).
Sugar ring shown to enhance DNA flexibility.
(20**) Levitt, M. How Many Base-Pairs per Turn Does DNA have in Solution and in Chromatin? Some Theoretical Calculations. Proc. Nat. Acad. Sci. USA 75, 640-644 (1978). [a]
DNA shown to be easily deformed and to have propeller twisted bases.
(23*) Prunell, A., R. D. Kornberg, L. Lutter, A. Klug, M. Levitt and F. H. C. Crick. Periodicity of Deoxyribonuclease I Digestion of Chromatin. Science 204, 855-858 (1979).
(32*) Levitt, M. Computer Simulation of DNA Double Helix Dynamics. Cold Spring Harbor Symp. Quant. Biol. 47, 251-261 (1983).
First simulations of DNA dynamics in vacuo revealed problems due to lack of solvent.
(84) Hirshberg, M. and M. Levitt. Simulating the Dynamics of the DNA Double Helix in Solution. In Dynamics and the Problem of Recognition in Biological Macromolecules, ed. Jardetzky, O. and Lefevre, J. Plenum Press, New York, pp. 173-191 (1997).
Simulations of DNA in water, first described in 1990 in Miriam Hirshberg's Ph.D. thesis, show that 12 base-pair fragments of the double helix are stable in water at room temperature for 100's of picoseconds. There are fluctuations at the ends of the stack as well as the narrowing of the minor grove in A-tracts, both of which observations agree with NMR experiments.
Thirteen papers on matching structures and sequence are continue a new emphasis involving large-scale comparison of genomic data aimed at understanding function from sequence.
(8*) Schulz, G. E., C. D. Barry, J. Friedman, P. Y. Chou, G. D. Fasman, A. V. Finkelstein, V. I. Lim, O. B. Ptitsyn, E. A. Kabat, T. T. Wu, M. Levitt, B. Robson and K. Nagano. Comparison of Predicted and Experimentally Determined Secondary Structure of Adenylate Kinase. Nature 250, 140-142 (1974).
(41) Lesk, A. M., M. Levitt and C. Chothia. Alignment of the Amino Acid Sequences of Distantly Related Proteins Using Variable Gap Penalties. Protein Engineering, 1, 77-78 (1986).
First use of structural information in sequence alignment.
(64) Subbiah, S., D. V. Laurents and M. Levitt. Structural Similarity of DNA-binding Domains of Bacteriophage Repressors and the Globin Core. Current Biol. 3, 141-148 (1993).
Simple method for simultaneous alignment and three-dimensional superposition of protein structures.
(69) Laurents, D. V., S. Subbiah and M. Levitt. Different Protein Sequences Can Give Rise to Highly Similar Folds Through Different Stabilizing Interactions. Protein Science 3, 1938-1944 (1994).
(87) Gerstein, M. and M. Levitt. A Structural Census of the Current World of Protein Sequences. Proc. Natl. Acad. Sci., 99, 11911-11916 (1997).
Different protein folds are used different by different organisms.
(89) Gerstein, M. and M. Levitt. Comprehensive Assessment of Automatic Structural Alignment against a Manual Standard, the SCOP Classification of Proteins. Protein Science, 7, 445-456 (1998).
Automatic structural alignment with Structal is able to recognize similarity objectively.
(91) Levitt, M and M. Gerstein. A Unified Statistical Framework for Sequence Comparison and Structure Comparison. Proc. Natl. Acad. Sci., 95, 5913-5920 (1998). [a]
This paper present a closed form equation giving the chance that a particular sequence or structure alignment score will occur at random.
(104). Brenner, S. E. and M. Levitt. Expectations from Structural Genomics. Protein Science, 9, 197-200 (2000).
We show that half the new proteins that are unique on the basis of their sequence actually have a previously known fold.
(96) Brenner S.E., D. Barken, and M. Levitt M. The PRESAGE Database for Structural Genomics. Nucleic Acids Res. 27, 251-3 (1999).
Structural genomics requires close collaboration of experimentalists and theoreticians and Presage is way to keep track of shared data.
(103). Brenner S.E, Koehl, P. and M. Levitt. The Astral Compendium for Protein Structure and Sequence Analysis Nucleic Acids Res., 28, 254-256 (2000).
Astral helps one select the best sets of protein coordinates for knowledge-based studies.
(106). Yona, G. and M. Levitt. A Unified Sequence-Structure Classification of Protein Sequences: Combining Sequence and Structure in a Map of the Protein Space. RECOMB 2000, pp. 308-317, ACM (2000).
BioSpace combines sequence and structure comparison to give a comprehensive classification of all protein sequences.
(109). Samudrala R, Levitt M. Decoys 'R' Us: A database of incorrect protein conformations for evaluating scoring functions. Protein Science, 9: 1399-1401 (2000).
Decoy folds have been very useful for the development and testing of energy functions for predicting protein structure.
(110). Yona, G. and M. Levitt. Towards A Complete Map of the Protein Space Based on a Unified Sequence And Structure Analysis of All Known Proteins. Proceedings of ISMB. In Press (2000).
The mapping of protein space in BioSpace is analyzed further.
Three papers on sequence design mark the start of a new area that is principally the work of Patrice Koehl.
(100). Koehl P. and M. Levitt. De Novo Protein Design. I. In Search of Stability and Specificity. J. Mol. Biol. 293, 1161-1181 (1999).
A new method for designing sequences use a detailed all-atom model with a physical potential..
(101). Koehl P. and M. Levitt. De Novo Protein Design. II. Plasticity in Sequence Space. J. Mol. Biol. 293, 1183-1193 (1999).
Many sequences are shown to be compatible with a given three-dimensional structure.
(102). Koehl P. and M. Levitt. Structure-Based Conformational Preferences of Amino Acids. Proc. Natl. Acad. Sci. USA, 96, 12524-12529 (1999)
Sequence design shows that the preferences of amino acids for secondary structure is driven by stability and specificity requirements.
Two papers comment on progress in science.
(97). Koehl P. and M. Levitt. A Brighter Future for Protein Structure Prediction. Nat Struct Biol. 6, 108-111 (1999).
A survey of the 1998 CASP3 meeting shows that progress is starting to be made on ab initio perdition..
(113). Levitt, M. The Birth of Computational Structural Biology, Nature Struct. Biol., 8, 392-393 (2001).
The early years of the field as seen by someone who was there.