title: Biased Molecular Simulations for Free-Energy Mapping:  A Comparison on the KcsA Channel as a Test Case.
abstract: The calculation of free-energy landscapes in proteins is a challenge for modern numerical simulations. As to the case of potassium ion channels is concerned, it is particularly interesting because of the nanometric dimensions of the selectivity filter, where the complex electrostatics is highly relevant. The present study aims at comparing three different techniques used to bias molecular dynamics simulations, namely Umbrella Sampling, Steered Molecular Dynamics, and Metadynamics, never applied all together in the past to the same channel protein. Our test case is represented by potassium ions permeating the selectivity filter of the KcsA channel.
authors.affiliation: CNR-INFM National Research Center on nanoStructures and bioSystems at Surfaces (S3), Via Campi 213/A, I-41100 Modena, Italy, Dipartimento di Ingegneria Elettronica, Informatica e Sistemistica DEIS, Alma Mater Studiorum Università di Bologna, Viale Risorgimento 2, I-40136 Bologna, Italy, Dipartimento di Fisica and Sardinian Laboratory for Computational Materials Science - SLACS, Università di Cagliari, Cittadella Monserrato, I-09042 Monserrato (CA), Italy, and Dipartimento di Fisica, Università di Modena e Reggio Emilia, Via Campi 213/A, I-41100 Modena, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Piccinini
authors.affiliation: CNR-INFM National Research Center on nanoStructures and bioSystems at Surfaces (S3), Via Campi 213/A, I-41100 Modena, Italy, Dipartimento di Ingegneria Elettronica, Informatica e Sistemistica DEIS, Alma Mater Studiorum Università di Bologna, Viale Risorgimento 2, I-40136 Bologna, Italy, Dipartimento di Fisica and Sardinian Laboratory for Computational Materials Science - SLACS, Università di Cagliari, Cittadella Monserrato, I-09042 Monserrato (CA), Italy, and Dipartimento di Fisica, Università di Modena e Reggio Emilia, Via Campi 213/A, I-41100 Modena, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Ceccarelli
authors.affiliation: CNR-INFM National Research Center on nanoStructures and bioSystems at Surfaces (S3), Via Campi 213/A, I-41100 Modena, Italy, Dipartimento di Ingegneria Elettronica, Informatica e Sistemistica DEIS, Alma Mater Studiorum Università di Bologna, Viale Risorgimento 2, I-40136 Bologna, Italy, Dipartimento di Fisica and Sardinian Laboratory for Computational Materials Science - SLACS, Università di Cagliari, Cittadella Monserrato, I-09042 Monserrato (CA), Italy, and Dipartimento di Fisica, Università di Modena e Reggio Emilia, Via Campi 213/A, I-41100 Modena, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Affinito
authors.affiliation: CNR-INFM National Research Center on nanoStructures and bioSystems at Surfaces (S3), Via Campi 213/A, I-41100 Modena, Italy, Dipartimento di Ingegneria Elettronica, Informatica e Sistemistica DEIS, Alma Mater Studiorum Università di Bologna, Viale Risorgimento 2, I-40136 Bologna, Italy, Dipartimento di Fisica and Sardinian Laboratory for Computational Materials Science - SLACS, Università di Cagliari, Cittadella Monserrato, I-09042 Monserrato (CA), Italy, and Dipartimento di Fisica, Università di Modena e Reggio Emilia, Via Campi 213/A, I-41100 Modena, Italy.
authors.forename: Rossella
authors.initials: R
authors.lastname: Brunetti
authors.affiliation: CNR-INFM National Research Center on nanoStructures and bioSystems at Surfaces (S3), Via Campi 213/A, I-41100 Modena, Italy, Dipartimento di Ingegneria Elettronica, Informatica e Sistemistica DEIS, Alma Mater Studiorum Università di Bologna, Viale Risorgimento 2, I-40136 Bologna, Italy, Dipartimento di Fisica and Sardinian Laboratory for Computational Materials Science - SLACS, Università di Cagliari, Cittadella Monserrato, I-09042 Monserrato (CA), Italy, and Dipartimento di Fisica, Università di Modena e Reggio Emilia, Via Campi 213/A, I-41100 Modena, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Jacoboni