title: Distance-Based Configurational Entropy of Proteins from Molecular Dynamics Simulations.
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: reference entropies for amino acids in unfolded proteins are obtained from a database of residues not participating in secondary structure elements;the conformational entropy of folding of β2-microglobulin is computed from molecular dynamics simulations using reference entropies for the unfolded state;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);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.
authors.affiliation: Dipartimento di Scienze Mediche e Biologiche, Universita' di Udine, Piazzale Kolbe 4, 33100 Udine, Italy; Istituto Nazionale Biostrutture e Biosistemi, Viale medaglie d'Oro 305, 00136 Roma, Italy.
authors.forename: Federico
authors.initials: F
authors.lastname: Fogolari
authors.affiliation: Dipartimento di Scienze Mediche e Biologiche, Universita' di Udine, Piazzale Kolbe 4, 33100 Udine, Italy; Istituto Nazionale Biostrutture e Biosistemi, Viale medaglie d'Oro 305, 00136 Roma, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Corazza
authors.affiliation: Dipartimento di Scienze Mediche e Biologiche, Universita' di Udine, Piazzale Kolbe 4, 33100 Udine, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Fortuna
authors.affiliation: Dipartimento di Scienze Mediche e Biologiche, Universita' di Udine, Piazzale Kolbe 4, 33100 Udine, Italy.
authors.forename: Miguel Angel
authors.initials: MA
authors.lastname: Soler
authors.affiliation: Department of Chemistry and Chemical Biology, McMaster University, 1280 Main St. W. Hamilton, ON L8S 4M1, Canada.
authors.forename: Bryan
authors.initials: B
authors.lastname: VanSchouwen
authors.affiliation: Center S3, CNR Institute Nanoscience, Via Campi 213/A, 41125 Modena, Italy.
authors.forename: Giorgia
authors.initials: G
authors.lastname: Brancolini
authors.affiliation: Center S3, CNR Institute Nanoscience, Via Campi 213/A, 41125 Modena, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Corni
authors.affiliation: Department of Chemistry and Chemical Biology, McMaster University, 1280 Main St. W. Hamilton, ON L8S 4M1, Canada.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Melacini
authors.affiliation: Dipartimento di Scienze Mediche e Biologiche, Universita' di Udine, Piazzale Kolbe 4, 33100 Udine, Italy; Istituto Nazionale Biostrutture e Biosistemi, Viale medaglie d'Oro 305, 00136 Roma, Italy.
authors.forename: Gennaro
authors.initials: G
authors.lastname: Esposito
mesh_terms: D000465:Algorithms; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism; D019277:Entropy; D020662:Guanine Nucleotide Exchange Factors / Q000737:chemistry / Q000378:metabolism; D008074:Lipoproteins / Q000737:chemistry / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D011487:Protein Conformation; D017510:Protein Folding; D058767:Protein Unfolding; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism; D001613:beta 2-Microglobulin / Q000737:chemistry / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D002352:Carrier Proteins; D020662:Guanine Nucleotide Exchange Factors; D008074:Lipoproteins; D011506:Proteins; D001613:beta 2-Microglobulin; C046506:oligopeptide-binding protein, bacteria