Articolo in rivista, 2022, ENG, 10.3389/fmolb.2022.933924

Chanalyzer: A Computational Geometry Approach for the Analysis of Protein Channel Shape and Dynamics

A.Raffo, L. Gagliardi, U. Fugacci,L. Sagresti, S. Grandinetti, G. Brancato, S. Biasotti, W. Rocchia

Istituto di Matematica Applicata e Tecnologie Informatiche "E. Magenes, Consiglio Nazionale delle Ricerche, Genova, Italy; CONCEPT Lab, Istituto Italiano di Tecnologia, Genova, Italy; Scuola Normale Superiore, Pisa, Italy; Istituto Nazionale di Fisica Nucleare, Pisa, Italy; Consorzio Interuniversitario per lo sviluppo dei Sistemi a Grande Interfase (CSGI), Sesto Fiorentino, Italy; Dipartimento di Ingegneria Civile ed Industriale, Università di Pisa, Pisa, Italy

Morphological analysis of protein channels is a key step for a thorough understanding of their biological function and mechanism. In this respect, molecular dynamics (MD) is a very powerful tool, enabling the description of relevant biological events at the atomic level, which might elude experimental observations, and pointing to the molecular determinants thereof. In this work, we present a computational geometry-based approach for the characterization of the shape and dynamics of biological ion channels or pores to be used in combination with MD trajectories. This technique relies on the earliest works of Edelsbrunner and on the NanoShaper software, which makes use of the alpha shape theory to build the solvent-excluded surface of a molecular system in an aqueous solution. In this framework, a channel can be simply defined as a cavity with two entrances on the opposite sides of a molecule. Morphological characterization, which includes identification of the main axis, the corresponding local radius, and the detailed description of the global shape of the cavity, is integrated with a physico-chemical description of the surface facing the pore lumen. Remarkably, the possible existence or temporary appearance of fenestrations from the channel interior towards the outer lipid matrix is also accounted for. As a test case, we applied the present approach to the analysis of an engineered protein channel, the mechanosensitive channel of large conductance.

Frontiers in Molecular Biosciences 9

Keywords

channel and pore characterization, computational geometry, molecular surface, molecular dynamics, skeletonization, alpha shapes theory, ion channels

CNR authors

Rocchia Walter, Raffo Andrea, Biasotti Silvia Maria, Fugacci Ulderico

CNR institutes

IMATI – Istituto di matematica applicata e tecnologie informatiche "Enrico Magenes"

ID: 470685

Year: 2022

Type: Articolo in rivista

Creation: 2022-09-12 11:38:32.000

Last update: 2022-09-12 14:04:18.000

External links

OAI-PMH: Dublin Core

OAI-PMH: Mods

OAI-PMH: RDF

DOI: 10.3389/fmolb.2022.933924

External IDs

CNR OAI-PMH: oai:it.cnr:prodotti:470685

DOI: 10.3389/fmolb.2022.933924

Scopus: 2-s2.0-85136809981

ISI Web of Science (WOS): 000838061700001