Distance-based configurational entropy of proteins from molecular dynamics simulations

Federico Fogolari, Alessandra Corazza, Sara Fortuna, Miguel Angel Soler, Bryan Van Schouwen, Giorgia Brancolini, Stefano Corni, Giuseppe Melacini, Gennaro Esposito

Research output: Contribution to journalArticle

Abstract

Estimation of configurational entropy from molecular dynamics trajectories is a difficult task which is often performed using quasi-harmonic or histogram analysis. An entirely different approach, proposed recently, estimates local density distribution around each conformational sample by measuring the distance from its nearest neighbors. In this work we show this theoretically well grounded the method can be easily applied to estimate the entropy from conformational sampling. We consider a set of systems that are representative of important biomolecular processes. In particular: i. reference entropies for amino acids in unfolded proteins are obtained from a database of residues not participating in secondary structure elements; ii. the conformational entropy of folding of β2-microglobulin is computed from molecular dynamics simulations using reference entropies for the unfolded state; iii. backbone conformational entropy is computed from molecular dynamics simulations of four different states of the EPAC protein and compared with order parameters (often used as a measure of entropy); iv. the conformational and rototranslational entropy of binding is computed from simulations of 20 tripeptides bound to the peptide binding protein OppA and of β2-microglobulin bound to a citrate coated gold surface. This work shows the potential of the method in the most representative biological processes involving proteins, and provides a valuable alternative, principally in the shown cases, where other approaches are problematic.

Original languageEnglish (US)
Article numbere0132356
JournalPloS one
Volume10
Issue number7
DOIs
StatePublished - Jul 15 2015

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Fogolari, F., Corazza, A., Fortuna, S., Soler, M. A., Van Schouwen, B., Brancolini, G., Corni, S., Melacini, G., & Esposito, G. (2015). Distance-based configurational entropy of proteins from molecular dynamics simulations. PloS one, 10(7), [e0132356]. https://doi.org/10.1371/journal.pone.0132356