Validation of the SPROUT de novo design program

Jacqueline M S Law, David Y K Fung, Zsolt Zsoldos, Aniko Simon, Zsolt Szabo, I. Csizmadia, A. Peter Johnson

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

The validation of SPROUT was carried out on four receptor-ligand complexes: thrombin-NAPAP, calmodulin (CAM)-AAA, Ras P-21-GDP and dihydrofolate reductase (DHFR)-methotrexate (MTX). These complexes were downloaded from the Brookhaven Protein Data Bank (PDB). For the thrombin-NAPAP complex, two structures very similar to NAPAP were generated. These two structures were similar in 3D structure to NAPAP but contained an extra hexane ring. For CAM-AAA and Ras P-21-GDP, the ligands generated were essentially identical to their original ligands. For DHFR, two ligands, one most similar in 2D structure and one most similar in 3D conformation were found. The successful regeneration of the ligands for each case proves the ability and applicability of SPROUT for designing strongly binding, successful drug candidates. When the program is executed with less restricted constraints, it generates a large number of novel structures that are structurally diverse, making it an ideal tool for de novo design.

Original languageEnglish
Pages (from-to)651-657
Number of pages7
JournalJournal of Molecular Structure: THEOCHEM
Volume666-667
DOIs
Publication statusPublished - Dec 29 2003

Fingerprint

Ligands
ligands
Calmodulin
calmodulin
thrombin
Tetrahydrofolate Dehydrogenase
Thrombin
Hexanes
Hexane
regeneration
Methotrexate
Conformations
Regeneration
drugs
Databases
proteins
Proteins
N(alpha)-(2-naphthylsulfonylglycyl)-4-amidinophenylalanine piperidide
rings
Pharmaceutical Preparations

Keywords

  • De novo design
  • Drug design
  • Fragment-based exhaustive search
  • Structure-based
  • Validation

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Computational Theory and Mathematics
  • Atomic and Molecular Physics, and Optics

Cite this

Law, J. M. S., Fung, D. Y. K., Zsoldos, Z., Simon, A., Szabo, Z., Csizmadia, I., & Johnson, A. P. (2003). Validation of the SPROUT de novo design program. Journal of Molecular Structure: THEOCHEM, 666-667, 651-657. https://doi.org/10.1016/j.theochem.2003.08.104

Validation of the SPROUT de novo design program. / Law, Jacqueline M S; Fung, David Y K; Zsoldos, Zsolt; Simon, Aniko; Szabo, Zsolt; Csizmadia, I.; Johnson, A. Peter.

In: Journal of Molecular Structure: THEOCHEM, Vol. 666-667, 29.12.2003, p. 651-657.

Research output: Contribution to journalArticle

Law, JMS, Fung, DYK, Zsoldos, Z, Simon, A, Szabo, Z, Csizmadia, I & Johnson, AP 2003, 'Validation of the SPROUT de novo design program', Journal of Molecular Structure: THEOCHEM, vol. 666-667, pp. 651-657. https://doi.org/10.1016/j.theochem.2003.08.104
Law, Jacqueline M S ; Fung, David Y K ; Zsoldos, Zsolt ; Simon, Aniko ; Szabo, Zsolt ; Csizmadia, I. ; Johnson, A. Peter. / Validation of the SPROUT de novo design program. In: Journal of Molecular Structure: THEOCHEM. 2003 ; Vol. 666-667. pp. 651-657.
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