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Modeling Side Chains in Peptides and Proteins with the Locally Enhanced Sampling/Simulated Annealing Method

  • Adrian Roitberg
  • Ron Elber

Abstract

In this chapter, we present the formal basis of a new optimization method that we call LES (locally enhanced sampling) together with applications to side-chain modeling in peptides and proteins. We examine the relationship between an energy function that is derived from data on small model systems and the correct structure of the protein. The question is: Given a functional form for the potential energy of a macromolecule, are the side-chain coordinates at the global energy minimum similar to the x-ray coordinates? This comparison enables us to detect inaccuracies in the force fields that we used (Brooks et al., 1983; Jorgensen and Tirado-Rives, 1988) and possibly to improve them.

Keywords

Force Field Potential Energy Surface Freezing Temperature Residue Type Minimum Energy Path 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Amara P, Hsu D, Straub JE (1993): Global energy minimum searches using an approximate solution of the imaginary time Schrödinger equation. J Phys Chem 97:6715CrossRefGoogle Scholar
  2. Blow D (1983): Molecular structure. Computer cues to combat hypertension. Nature 304:213–214PubMedCrossRefGoogle Scholar
  3. Blundell TL, Sibanda BL, Sternberg MJE, Thornton JM (1987): Knowledge based prediction of protein structures and the design of novel molecules. Nature 326:347–352PubMedCrossRefGoogle Scholar
  4. Brooks SR, Bruccoleri RE, Olafson SD, States DJ, Swaminathan S, Karplus M (1983): CHARMM: A program for macromolecular energy, minimizalion and dynamic calculations. J Comput Chem 4:187–217CrossRefGoogle Scholar
  5. Bruccoleri RE, Karplus MK (1987): Predicting the folding of short Polypeptide segments by uniform conformational sampling. Biopolymers 26:137–168PubMedCrossRefGoogle Scholar
  6. Burley SK, Pelsko GA (1986): Dimerization energetics of benzene and aromatic amino acid side-chains. J Am Chem Soc 108:7995–8001CrossRefGoogle Scholar
  7. Czerminski R, Elber R (1990): Self-avoiding walk between two fixed-points as a tool to calculate reaction paths in large molecular-systems. Int J Quant Chem 24:167–186CrossRefGoogle Scholar
  8. Czerminski R, Elber R (1991): Computational studies of ligand diffusion in globins: 1. Leghemoglobin. Proteins: Structure, Function and Genetics 10:70–80CrossRefGoogle Scholar
  9. Desmet J, De Maeyer M, Hazes B, Lasters I (1992): The dead-end elimination theorem and its use in protein side-chain positioning. Nature 356:539–542PubMedCrossRefGoogle Scholar
  10. Elber R, Karplus M (1990): Enhanced sampling in molecular dynamics: use of the time dependent Hartree approximation for a simulation of carbon monoxide through myoglobin. J Am Chem Soc 112:9161–9175CrossRefGoogle Scholar
  11. Elber R, Roitberg A, Simmering C, Goldstein R, Verkhiver G, Li H, Ulitsky A (1993): MOIL: A molecular dynamics program with emphasis in conformational searches and reaction path calculations. To be published in the proceedings of the NATO conference: Statistical Mechanics, Protein Structure and Protein-Substrate Interactions, Doniac S, ed., New York: Plenum Press. This program is available via anonymous ftp from 128.248.186.70Google Scholar
  12. Gelin BR, Karplus MK (1975): Side-chain torsional potentials and motion of amino acids in proteins: Bovine pancreatic trypsin inhibitor. Proc Natl Acad Sci 72:2002–2006PubMedCrossRefGoogle Scholar
  13. Gelin BR, Karplus MK (1979): Side-chain torsional potentials: effect of dipeptide, protein and solvent environment. Biochemistry 18:1257–1268CrossRefGoogle Scholar
  14. Gerber RB, Buch V, Ratner MA (1982): Time dependent self-consistent field approach for intramolecular energy transfer. I. Formulation and application to dissociation of van der Waals molecules. J Chem Phys 77:3302–3030CrossRefGoogle Scholar
  15. Gibson QH, Regan R, Elber R, Olson JS, Carver TE (1992): Distal pocket residues affect picosecond ligand recombination in myoglobin: An experiment and molecular dynamics study of position 29 mutants. J Biol Chem 267:22022–22034PubMedGoogle Scholar
  16. Greer J (1981): Comparative model building of mammalian serine proteases. J Mol Biol 153:1027–1042PubMedCrossRefGoogle Scholar
  17. Holm L, Sander C (1992): Fast and simple Monte Carlo algorithm for side-chain optimization in proteins: Application to model building by homology. Proteins: Structure, Function and Genetics 14:213–223CrossRefGoogle Scholar
  18. Janin J, Wodak S, Levitt M, Maigret B (1978): Conformation of amino acid sidechains in proteins. J Mol Biol 125:357–386PubMedCrossRefGoogle Scholar
  19. James MNG, Sielecki AR (1983): Structure refinement of penicillopepsin at 1.8 Å resolution. J Mol Biol 163:299–361PubMedCrossRefGoogle Scholar
  20. Jorgensen WL, Tirado-Rives J (1988): The OPLS potential functions for proteins, energy minimizations for crystals of cyclic peptides and crambin. J Am Chem Soc 110:1657–1666CrossRefGoogle Scholar
  21. Kuriyan J, Wilz S, Karplus M, Petsko GA (1986): X-ray structure and refinement of carbon-monoxy (Fe II)-myoglobin at 1.5 Å resolution. J Mol Biol 192:133–154PubMedCrossRefGoogle Scholar
  22. Lee B, Richards FM (1971): The interpretation of protein structures: estimation of static accessibility. J Mol Biol 55:379–400PubMedCrossRefGoogle Scholar
  23. Lee C, Levitt M (1991): Accurate prediction of the stability effects of site-directed mutagenesis on a protein core. Nature 352:448–451PubMedCrossRefGoogle Scholar
  24. Lee C, Subbiah S (1991): Prediction of side-chain conformation by packing optimization. J Mol Biol 217:373–388PubMedCrossRefGoogle Scholar
  25. Lesk AM, Chothia C (1986): The response of protein structures to amino-acid sequence changes. Phil Trans Roy Soc A 317:345–356CrossRefGoogle Scholar
  26. Narayana SV, Argos P (1984): Residue contacts in protein structures and implications for protein folding. Int J Pept Prot Res 24:25–39CrossRefGoogle Scholar
  27. Petterson I, Liljefors T (1987): Benzene-Benzene (Phenyl-Phenyl) interactions in MM2/MMP2 molecular mechanics calculations. J Comp Chem 8:1139–1145CrossRefGoogle Scholar
  28. Piela L, Kostrowicki J, Scheraga HA (1989): The multiple-minima problem in the conformational analysis of molecules. Determination of the potential energy surface by the diffusion equation. J Phys Chem 93:3339–3346CrossRefGoogle Scholar
  29. Ponder JW, Richards FM (1987): Tertiary template for proteins. Use of packing criteria in the enumeration of allowed sequences for different structural classes. J Mol Biol 193:775–791PubMedCrossRefGoogle Scholar
  30. Reid L, Thornton JM (1989): Rebuilding flavodoxin from C a coordinates: A test study. Proteins: Structure, Function and Genetics 5:170–182CrossRefGoogle Scholar
  31. Richards FM (1977): Volumes, packing and protein structure. Annu Rev Biophys Bioeng 6:151–176PubMedCrossRefGoogle Scholar
  32. Roitberg A (1992): Ph.D. thesis, University of Illinois at ChicagoGoogle Scholar
  33. Roitberg A, Elber R (1991): Modeling side-chains in peptides and proteins: applicaton of the locally enhanced sampling and the simulated annealing methods to find minimum energy conformations. J Chem Phys 95:9277–9287CrossRefGoogle Scholar
  34. Ryckaert JP, Ciccotti C, Berendsen HJC (1977): Numerical integration of the Cartesian equations of motion of a system with constraints: Molecular dynamics of n-alkanes. J Comput Phys 23:327–341CrossRefGoogle Scholar
  35. Shakhnovich EI, Finkelstein AV (1989): Theory of cooperative transitions in protein molecules. I. Why denaturation of globular proteins is a first-order phase transition. Biopolymers 28:1667PubMedCrossRefGoogle Scholar
  36. Simmerling C, Elber R (1994): Hydrophobic “collapse” in a cyclic hexapeptide: Computer simulations of CHDLFC and CAAAAC in water. JACS 116:253–254CrossRefGoogle Scholar
  37. Singh J, Thornton JM (1990): SIRIUS: An automated method for the analysis of the preferred packing arrangements between protein groups. J Mol Biol 211:595–615PubMedCrossRefGoogle Scholar
  38. Smith J, Hendrickson WA, Honzatko R, Sheriff S (1986): Structural heterogeneity in protein crystals. Biochemistry 25:5018–5027PubMedCrossRefGoogle Scholar
  39. Straub J, Karplus M (1991): Energy equipartition in the classical time-dependent Hartree approximation. J Chem Phys 94:6737–6739CrossRefGoogle Scholar
  40. Shalloway D (1992): In Recent Advances in Global Optimization, Floudas A, Pardalos PM, eds. Princeton, NJ: Princeton University Press, pp. 433–477Google Scholar
  41. Summers NL, Carlson WD, Karplus MK (1987): Analysis of side-chain orientations in homologous proteins. J Mol Biol 196:175–198PubMedCrossRefGoogle Scholar
  42. Summers NL, Karplus MK (1989): Construction of side-chains in homology modeling. Application to the C-terminal lobe of rhizopuspepsin. J Mol Biol 210:785–811PubMedCrossRefGoogle Scholar
  43. Tuffery P, Etchebest C, Hazout S, Lavery R (1991): A new approach to the rapid determination of protein side-chain conformations. J Biomo/Struc Dynamics 8:1267–1289Google Scholar
  44. Ulitsky A, Elber R (1993): The thermal equilibrium properties of the time dependent Hartree and the locally enhanced sampling approximations. Formal properties, a correction and computational examples of rare gas clusters. J Chem Phys 98:3380–3388CrossRefGoogle Scholar
  45. Verkhivker G, Elber R, Nowak W (1992): Locally enhanced sampling in free energy calculations: Application of mean field approximation to accurate calculation of free energy differences. J Chem Phys 97:7838–7841CrossRefGoogle Scholar
  46. Warme PK, Morgan RS (1978): A survey of side-chain interactions in 21 proteins. J Mol Biol 118:289–304PubMedCrossRefGoogle Scholar
  47. Weiner SJ, Kollman PA, Case DA, Chandra Singh U, Ghio C, Alagona G, Profeta S, Weiner P (1984): A new force field for molecular mechanical simulation of nucleic acids and proteins. J Am Chem Soc 106:765–784CrossRefGoogle Scholar
  48. Zimmerman SS, Pottle MS, Nemethy G, Scheraga HA (1977): Conformational analysis of the 20 naturally occurring amino acid residues using ECEPP. Macromolecules 10:1–9PubMedCrossRefGoogle Scholar

Copyright information

© Birkhäuser Boston 1994

Authors and Affiliations

  • Adrian Roitberg
  • Ron Elber

There are no affiliations available

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