Computational screening of potential non-immunoglobulin scaffolds using overlapped conserved residues (OCR)-based fingerprints

Ganapathiraman Munussami; Sriram Sokalingam; Selvakumar Edwardraja; Jung Rae Kim; Sungwook Chung; Sun-Gu Lee

Korean Journal of Chemical Engineering, Vol.35, No.3, 717-724, March, 2018

DOI10.1007/s11814-017-0350-4 Export Citation

Computational screening of potential non-immunoglobulin scaffolds using overlapped conserved residues (OCR)-based fingerprints

Ganapathiraman Munussami, Sriram Sokalingam^†, Selvakumar Edwardraja, Jung Rae Kim, Sungwook Chung, and Sun-Gu Lee^†

Department of Chemical and Biomolecular Engineering, Pusan National University, Busan 46241, Korea

E-mail:,

Cystatins and lipocalins have attracted considerable interest for their potential applications in non-immunoglobulin protein scaffold engineering. In the present study, their potential homologs were screened computationally from non-redundant protein sequence database based on the overlapped conserved residues (OCR)-fingerprints, which can detect the protein family with low sequence identity, such as cystatins and lipocalins. Two types of OCR-fingerprints for each family were designed and showed very high detection efficiency (>90%). The protein sequence database was scanned by the fingerprints, which yielded the hypothetical sequences for cystatins and lipocalins. The hypothetical sequences were validated further based on their sequence motifs and structural models, which allowed an identification of the potential homologs of cystatins and lipocalins.

Keywords:Protein Scaffold;Cystatins;Lipocalins;OCR-fingerprints

[References]

Binz HK, Amstutz P, Pluckthun A, Nat. Biotechnol., 23, 1257 (2005)
Finn RD, Attwood TK, Babbitt PC, Bateman A, Bork P, Bridge AJ, Chang HY, Dosztanyi Z, El-Gebali S, Fraser M, Gough J, et al., Nucleic. Acids Res., 45, D190 (2017)
Flower DR, Biochem. J., 318, 1 (1996)
Gattiker A, Gasteiger E, Bairoch AM, Appl. Bioinformatics, 1, 107 (2002)
Goyal A, Kim BG, Hwang KS, Lee SG, Biotechnol. Bioproc. E, 20, 431 (2015)
Goyal A, Sokalingam S, Hwang KS, Lee SG, Sci. Rep-Uk, 4, 5643 (2014)
Holm L, Rosenstrom P, Nucleic. Acids Res., 38, W545 (2010)
Kelley LA, Mezulis S, Yates CM, Wass MN, Sternberg MJE, Nat. Protoc., 10, 845 (2015)
Kister AE, Gelfand I, P. Natl. Acad Sci. USA, 106, 18996 (2009)
Laskowski RA, Watson JD, Thornton JM, Nucleic. Acids Res., 33, W89 (2005)
Nygren PA, Skerra A, J. Immunol. Methods, 290, 3 (2004)
Sievers F, Wilm A, Dineen D, Gibson TJ, Karplus K, Li WZ, Lopez R, McWilliam H, Remmert M, Soding J, Thompson JD, Higgins DG, Mol. Syst. Biol., 7, 539 (2011)
Skerra A, Schmidt SR, Pharm. Bioprocess, 3, 383 (2015)
Skrlec K, Strukelj B, Berlec A, Trends Biotechnol., 33, 408 (2015)
Tiede C, Tang AA, Deacon SE, Mandal U, Nettleship JE, Owen RL, George SE, Harrison DJ, Owens RJ, Tomlinson DC, McPherson MJ, Protein Eng. Des. Sel., 27, 145 (2014)
Zhang CX, Freddolino PL, Zhang Y, Nucleic. Acids Res., 45, W291 (2017)

[1] Binz HK, Amstutz P, Pluckthun A, Nat. Biotechnol., 23, 1257 (2005)

[2] Finn RD, Attwood TK, Babbitt PC, Bateman A, Bork P, Bridge AJ, Chang HY, Dosztanyi Z, El-Gebali S, Fraser M, Gough J, et al., Nucleic. Acids Res., 45, D190 (2017)

[3] Flower DR, Biochem. J., 318, 1 (1996)

[4] Gattiker A, Gasteiger E, Bairoch AM, Appl. Bioinformatics, 1, 107 (2002)

[5] Goyal A, Kim BG, Hwang KS, Lee SG, Biotechnol. Bioproc. E, 20, 431 (2015)

[6] Goyal A, Sokalingam S, Hwang KS, Lee SG, Sci. Rep-Uk, 4, 5643 (2014)

[7] Holm L, Rosenstrom P, Nucleic. Acids Res., 38, W545 (2010)

[8] Kelley LA, Mezulis S, Yates CM, Wass MN, Sternberg MJE, Nat. Protoc., 10, 845 (2015)

[9] Kister AE, Gelfand I, P. Natl. Acad Sci. USA, 106, 18996 (2009)

[10] Laskowski RA, Watson JD, Thornton JM, Nucleic. Acids Res., 33, W89 (2005)

[11] Nygren PA, Skerra A, J. Immunol. Methods, 290, 3 (2004)

[12] Sievers F, Wilm A, Dineen D, Gibson TJ, Karplus K, Li WZ, Lopez R, McWilliam H, Remmert M, Soding J, Thompson JD, Higgins DG, Mol. Syst. Biol., 7, 539 (2011)

[13] Skerra A, Schmidt SR, Pharm. Bioprocess, 3, 383 (2015)

[14] Skrlec K, Strukelj B, Berlec A, Trends Biotechnol., 33, 408 (2015)

[15] Tiede C, Tang AA, Deacon SE, Mandal U, Nettleship JE, Owen RL, George SE, Harrison DJ, Owens RJ, Tomlinson DC, McPherson MJ, Protein Eng. Des. Sel., 27, 145 (2014)

[16] Zhang CX, Freddolino PL, Zhang Y, Nucleic. Acids Res., 45, W291 (2017)