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

C. R. Watts, M. Mezei, R. F. Murphy, Sándor Lovas

Research output: Contribution to journalArticle

14 Citations (Scopus)

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
Pages (from-to)733-748
Number of pages16
JournalJournal of Biomolecular Structure and Dynamics
Volume18
Issue number5
StatePublished - 2001

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Molecular Dynamics Simulation
Thermodynamics
Cluster Analysis
Gonadotropin-Releasing Hormone
gonadotropin-releasing hormone-III
Pressure
Temperature
Neoplasms

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Structural Biology

Cite this

Conformational space comparison of GnRH and lGnRH-III using molecular dynamics, cluster analysis and Monte Carlo thermodynamic integration. / Watts, C. R.; Mezei, M.; Murphy, R. F.; Lovas, Sándor.

In: Journal of Biomolecular Structure and Dynamics, Vol. 18, No. 5, 2001, p. 733-748.

Research output: Contribution to journalArticle

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