Conformational space comparison of GnRH and lGnRH-III using molecular dynamics, cluster analysis and Monte Carlo thermodynamic integration

Charles R. Watts, Mihaly Mezei, Richard F. Murphy, Sándor Lovas

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

The conformational space available to GnRH and lGnRH-III was compared using 5.2 ns constant temperature and pressure molecular dynamics simulations with explicit TIP3P solvation and the AMBER v. 5.0 force field. Cluster analysis of both trajectories resulted in two groups of conformations. Results of free energy calculations, in agreement with previous experimental data, indicate that a conformation with a turn from residues 5 through 8 is preferred for GnRH in an aqueous environment. By contrast, a conformation with a helix from residues 2 through 7 with a bend from residues 6 through 10 is preferred for lGnRH-III in an aqueous environment. The side chains of His2 and Trp3 in lGnRH-III occupy different regions of phase space and participate in weakly polar interactions different from those in GnRH. The unique conformational properties of lGnRH-III may account for its specific anti cancer activity.

Original languageEnglish (US)
Pages (from-to)733-748
Number of pages16
JournalJournal of Biomolecular Structure and Dynamics
Volume18
Issue number5
DOIs
StatePublished - Jan 1 2001

All Science Journal Classification (ASJC) codes

  • Structural Biology
  • Molecular Biology

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