Molecular Dynamics in Drug Design: New Generations of Compstatin Analogs

Chemical Biology and Drug Design

Volumn 79, Issue 5, 2012, Pages 703-718

  Tamamis, Phanourios ^a,b,c,d,e   López de Victoria, Aliana ^a   Gorham, Ronald D ^a   Bellows Peterson, Meghan L ^c   Pierou, Panayiota ^b   Floudas, Christodoulos A ^c   Morikis, Dimitrios ^a   Archontis, Georgios ^b  

^a University of California Riverside   (United States)

^b UNIVERSITY OF CYPRUS   (Cyprus)

^c Princeton University   (United States)

^d UNIVERSITY OF CALIFORNIA   (United States)

^e PRINCETON UNIVERSITY   (United States)

Author keywords

Complement system, C3; Compstatin; Mechanism based drug design; Molecular modeling; Structure based drug design

Indexed keywords

COMPSTATIN; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; UNCLASSIFIED DRUG;

AMINO ACID SEQUENCE; AMINO TERMINAL SEQUENCE; ARTICLE; BINDING AFFINITY; CRYSTAL STRUCTURE; DRUG DESIGN; HUMAN; HYDROGEN BOND; HYDROPHOBICITY; MOLECULAR DOCKING; MOLECULAR DYNAMICS; MOUSE; MUTATION; NONHUMAN; PHYSICAL CHEMISTRY; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN PROTEIN INTERACTION; PROTEIN SECONDARY STRUCTURE; PROTEIN STABILITY; RAT; RETINA MACULA DEGENERATION; SOLUBILITY; X RAY CRYSTALLOGRAPHY;

AMINO ACID SEQUENCE; ANIMALS; COMPLEMENT C3; DRUG DESIGN; HUMANS; MICE; MOLECULAR DYNAMICS SIMULATION; MOLECULAR SEQUENCE DATA; PEPTIDES, CYCLIC; RATS;

ANIMALIA; RATTUS;

EID: 84859425740     PISSN: 17470277     EISSN: 17470285     Source Type: Journal    
DOI: 10.1111/j.1747-0285.2012.01324.x     Document Type: Article

References (65)

1. Muller-Eberhard H.J. (2002) Complement-chemistry and pathways. In: Gallin J.I., Goldstein I.M., Synderman R., editors. Inflammation: Basic Principles and Clinical Correlates. New York, USA: Raven Press; p. 21-54.
2. Anderson D.H., Radeke M.J., Gallo N.B., Chapin E.A., Johnson P.T., Curletti C.R., Hancox L.S., Hu J., Ebright J.N., Malek G., Hauser M.A., Rickman C.B., Bok D., Hageman G.S., Johnson L.V. (2010) The pivotal role of the complement system in aging and age-related macular degeneration: hypothesis re-visited. Prog Retin Eye Res;29:95-112.
3. Sahu A., Lambris J.D. (2000) Complement inhibitors: a resurgent concept in anti-inflammatory therapeutics. Immunopharmacology;49:133-148.
4. Janssen B.J.C., Halff E.F., Lambris J.D., Gros P. (2007) Structure of compstatin in complex with complement component C3c reveals a new mechanism of complement inhibition. J Biol Chem;282:29241-29247.
5. Ricklin D., Lambris J.D. (2008) Compstatin: a complement inhibitor on its way to clinical application. Adv Exp Med Biol;632:273-292.
6. Walport M.J. (2001) Complement. Second of two parts. N Engl J Med;344:1140-1144.
7. Nishida N., Walz T., Springer T.A. (2006) Structural transitions of complement component C3 and its activation products. PNAS;103:19737-19742.
8. Gros P., Milder F.J., Janssen B.J.C. (2008) Complement driven by conformational changes. Nat Rev Immunol;8:48-58.
9. Sahu A., Ray B.K., Lambris J.D. (1996) Inhibition of human complement by a C3- binding peptide isolated from a phage-displayed random peptide library. J Immunol;157:884-891.
10. Morikis D., Lambris J.D. (2005) Structure, dynamics, activity and function of compstatin and design of more potent analogs. In: Morikis D., Lambris J.D., editors. Structural Biology of the Complement System. Boca Raton, FL, USA: CRC Press/Taylor & Francis Group; p. 317-340.
11. Soulika A.M., Holl M.C.H., Sfyroera G., Sahu A., Lambris J.D. (2006) Compstatin inhibits complement activation by binding to the β-chain of complement factor 3. Mol Immunol;43:2023-2029.
12. Sahu A., Morikis D., Lambris J.D. (2003) Compstatin, a peptide inhibitor of complement, exhibits species-specific binding to complement component C3. Mol Immunol;39:557-566.
13. Bellows M.L., Fung H.K., Taylor M.S., Floudas C.A., López De Victoria A., Morikis D. (2010) New compstatin variants through two de novo protein design frameworks. Biophys J;98:2337-2346.
14. López de Victoria A., Gorham R.D. Jr, Bellows M.L., Ling J., Lo D.D., Floudas C.A., Morikis D. (2011) A new generation of potent complement inhibitors of the compstatin family. Chem Biol Drug Des;77:31-440.
15. Tamamis P., Morikis D., Floudas C.A., Archontis G. (2010) Species specificity of the complement inhibitor compstatin investigated by all-atom molecular dynamics simulations. Proteins;78:2655-2667.
16. Tamamis P., Pierou P., Mytidou C., Morikis D., Floudas C.A., Archontis G. (2011) Design of a modified mouse protein with ligand binding properties of its human analog by molecular dynamics simulations: the case of C3 inhibition by compstatin. Proteins;79:3166-3179.
17. Morikis D., Assa-Munt N., Sahu A., Lambris J.D. (1998) Solution structure of compstatin, a potent complement inhibitor. Protein Sci;7:619-627.
18. Klepeis J.L., Floudas C.A., Morikis D., Lambris J.D. (1999) Predicting peptide structures using NMR data and deterministic global optimization. J Comput Chem;20:1354-1370.
19. Sahu A., Soulika A., Morikis D., Spruce L., Moore W.T., Lambris J.D. (2000) Binding kinetics, structure-activity relationship, and biotransformation of the complement inhibitor compstatin. J Immunol;165:2491-2499.
20. Morikis D., Roy M., Sahu A., Troganis A., Jennings P.A., Tsokos G.C., Lambris J.D. (2002) The structural basis of compstatin activity examined by structure-function-based design of peptide analogs and NMR. J Biol Chem;277:14942-14953.
21. Morikis D., Lambris J.D. (2002) Structural aspects and design of low-molecular-mass complement inhibitors. Biochem Soc Trans;30:1026-1036.
22. Mallik B., Lambris J.D., Morikis D. (2003) Conformational interconversion in compstatin probed with molecular dynamics simulations. Proteins;52:130-141.
23. Tamamis P., Skourtis S., Morikis D., Lambris J.D., Archontis G. (2007) Conformational analysis of compstatin analogues with molecular dynamics simulations in explicit water. J Mol Graph Model;26:571-580.
24. Klepeis J., Floudas C.A., Morikis D., Tsokos C.G., Argyropoulos E., Spruce L., Lambris J.D. (2003) Integrated computational and experimental approach for lead optimization and design of compstatin variants with improved activity. J Am Chem Soc;125:8422-8423.
25. Soulika A.M., Morikis D., Sarrias M.R., Roy M., Spruce L.A., Sahu A., Lambris J.D. (2003) Studies of structure-activity relations of complement inhibitor compstatin. J Immunol;170:1881-1890.
26. Morikis D., Soulika A.M., Mallik B., Klepeis J.L., Floudas C.A., Lambris J.D. (2004) Improvement of the anti-C3 activity of compstatin using rational and combinatorial approaches. Biochem Soc Trans;32:28-32.
27. Mallik B., Katragadda M., Spruce L.A., Carafides C., Tsokos C.G., Morikis D., Lambris J.D. (2005) Design and NMR characterization of active analogues of compstatin containing non-natural amino acids. J Med Chem;48:274-286.
28. Furlong S.T., Dutta A.S., Coath M.M., Gormley J.J., Hubbs S.J., Lloyd D., Mauger R.C., Strimpler A.M., Sylvester M.A., Scott C.W., Edwards P.D. (2000) C3 activation is inhibited by analogs of compstatin but not by serine protease inhibitors or peptidyl alpha-ketoheterocycles. Immunopharmacology;48:199-212.
29. Mallik B., Morikis D. (2005) Development of a quasi-dynamic pharmacophore model for anti-complement peptide analogues. J Am Chem Soc;127:10967-10976.
30. Chiu T.L., Mulakala C., Lambris J.D., Kaznessis Y.N. (2008) Development of a new pharmacophore model that discriminates active compstatin analogs. Chem Biol Drug Des;72:249-256.
31. Klepeis J.L., Floudas C.A., Morikis D., Tsokos C.G., Lambris J.D. (2004) Design of peptide analogs with improved activity using a de novo protein design approach. Ind Eng Chem Res;43:3817-3826.
32. Holland M.C.H., Morikis D., Lambris J.D. (2004) Synthetic small molecule complement inhibitors. Curr Opin Invest Dr;5:1164-1173.
33. Morikis D., Floudas C.A., Lambris J.D. (2005) Structure-based integrative computational and experimental approach for the optimization of drug design. In: Sunderam V.S., van Albada G.D., Sloot P.M.A., Dongarra J.J., editors. ICCS Lecture Notes in Computer Science: Computational Science. Berlin-Heidelberg, Atlanta, GA, USA: Springer-Verlag; p. 680-688.
34. Morikis D., Mallik B., Zhang L. (2006) Biophysical and bioengineering methods for the study of the complement system at atomic resolution. WSEAS Trans Biol Biomed;6:408-413.
35. Qu H., Magotti P., Ricklin D., Wu E.L., Kourtzelis I., Wu Y.-Q., Kaznessis Y.N., Lambris J.D. (2011) Novel analogues of the therapeutic complement inhibitor compstatin with significantly improved affinity and potency. Mol Immunol;48:481-489.
36. Tamamis P., Archontis G. (2011) Solution conformational properties of the potential therapeutic complement inhibitor compstatin and selected analogs, investigated by MD simulations in implicit- and explicit-water. Biomed Eng Res;1: 14-21.
37. Rajgaria R., McAllister S.R., Floudas C.A. (2006) A novel high resolution Cα-Cα distance dependent force field based on a high quality decoy set. Proteins;65:726-741.
38. Rajgaria R., McAllister S.R., Floudas C.A. (2008) Distance dependent centroid to centroid force fields using high resolution decoys. Proteins;70:950-970.
39. Fung H.K., Taylor M.S., Floudas C.A. (2007) Novel formulations for the sequence selection problem in de novo protein design with flexible templates. Optim Methods Softw;22:51-71.
40. Fung H.K., Floudas C.A., Taylor M.S., Zhang L., Morikis D. (2008) Toward full sequence de novo protein design with flexible templates for human beta-defensin-2. Biophys J;94:584-599.
41. Bellows M.L., Taylor M.S., Cole P.A., Shen L., Siliciano R.F., Fung H.K., Floudas C.A. (2010) Discovery of entry inhibitors for HIV-1 via a new de novo protein design framework. Biophys J;99:3445-3453.
42. Lee M.R., Baker D., Kollman P.A. (2001) 2.1 and 1.8°A Cα RMSD structure predictions on two small proteins, HP-36 and S15. J Am Chem Soc;123:1040-1046.
43. Rohl C.A., Baker D. (2002) De novo determination of protein backbone structure from residual dipolar couplings using Rosetta. J Am Chem Soc;124:2723-2729.
44. Rohl C.A., Strauss C.E.M., Misura K.M.S., Baker D. (2004) Protein structure prediction using Rosetta. Methods Enzymol;383:66-93.
45. DiMaggio P.A., McAllister S.R., Floudas C.A., Feng X.J., Rabinowitz J.D., Rabitz H.A. (2008) Biclustering via optimal re-ordering of data matrices in systems biology: rigorous methods and comparative studies. BMC Bioinformatics;9:458-474.
46. DiMaggio P.A., McAllister S.R., Floudas C.A., Feng X.J., Rabinowitz J.D., Rabitz H.A. (2010) A network flow model for biclustering via optimal re-ordering of data matrices. J Glob Optim;47:343-354.
47. Daily M.D., Masica D., Sivasubramanian A., Somarouthu S., Gray J.J. (2005) CAPRI rounds 3-5 reveal promising successes and future challenges for Rosetta- Dock. Proteins;60:181-186.
48. Gray J.J., Moughon S., Wang C., Schueler-Furman O., Kuhlman B., Rohl C.A., Baker D. (2003) Protein-protein docking with simultaneous optimization of rigid-body displacement and side-chain conformations. J Mol Biol;331:281-299.
49. Gray J.J., Moughon S.E., Kortemme T., Schueler-Furman O., Misura K.M.S., Morozov A.V., Baker D. (2003) Protein-protein docking predictions for the CAPRI experiment. Proteins;52:118-122.
50. Mackerell A.D. Jr., Bashford D., Bellot R.L., Dunbrack R.L. Jr., Evanseck J.D., Field M.J., Fischer H. et al. (1998) An all-atom empirical potential for molecular modeling and dynamics study of proteins. J Phys Chem B;102:3586-3616.
51. Mackerell A.D. Jr, Feig M., Brooks C.L. III (2003) Extending the treatment of backbone energetics in protein force fields: limitations of gas-phase quantum mechanics in reproducing protein conformational distributions in molecular dynamics simulations. J Comput Chem;25:1400-1415.
52. Macias A.T., Mackerell A.D. Jr (2005) CH/pi interactions involving aromatic amino acids: refinement of the CHARMM tryptophan force field. J Comput Chem;26:1452-1463.
53. Brooks B.R. et al. (2009) CHARMM: the biomolecular simulation program. J Comput Chem;30:1545-1614.
54. Eswar N., Marti-Renom M.A., Webb B., Madhusudhan M.S., Eramian D., Shen M., Pieper U., Sali A. (2006) Comparative Protein Structure Modeling With MODELLER. Current Protocols in Bioinformatics, John Wiley & Sons, Inc., Supplement;15, 5.6.1-5.6.30, 2006.
55. Krivov G.G., Shapovalov M.V., Dunbrack R.L. Jr (2009) Improved prediction of protein side-chain conformations with SCWRL4. Proteins;77:8-795.
56. Seeber M., Cecchini M., Rao F., Settanni G., Caflisch A. (2007) Wordom: a program for efficient analysis of molecular dynamics simulations. Bioinformatics;23:2625-2627.
57. Massova I., Kollman P.A. (2000) Combined molecular mechanical and continuum solvent approach (MM-PBSA/GBSA) to predict ligand binding. Persp Drug Discov Des;18:113-135.
58. Im W., Lee M.S., Brooks C.L. III (2003) Generalized born model with a simple smoothing function. J Comput Chem;24:1691-1702.
59. Chen J., Im W., Brooks C.L. III (2006) Balancing solvation and intramolecular interactions: toward a consistent generalized born force field. J Am Chem Soc;128:3728-3736.
60. Gohlke H., Case D. (2004) Converging free energy estimates: MM-PB(GB)SA studies on the protein-protein complex Ras-Raf. J Comput Chem;25:238-250.
61. Page C.S., Bates P.A. (2006) Can MM-PBSA calculations predict the specificities of protein kinase inhibitors? J Comput Chem;27:1990-2007.
62. Gilson M.K., Zhou H.X. (2007) Calculation of protein-ligand binding affinities. Annu Rev Biophys Biomol Struct;36:21-42.
63. Zoete V., Irving M.B., Michielin O. (2010) MM-GBSA binding free energy decomposition and T cell receptor engineering. J Mol Recognit;23:142-152.
64. Singh N., Warshel A. (2010) Absolute binding free energy calculations: on the accuracy of computational scoring of protein-ligand interactions. Proteins;78:1705-1723.
65. Lazaridis T., Massunov A., Gandolfo F. (2002) Contributions to the binding free energy of ligands to avidin and streptavidin. Proteins;47:194-198.