INB Integrated platform for macromolecular flexibility

Biological function is largely based on molecular recognition. Biological macromolecules interact to each other following strict rules on the complementarity of 3D structures and interactions. The understanding of molecular recognition has been based traditionally on the analysis of static models of protein and nucleic acids 3D structures as found in the Protein Data Bank. However, molecular recognition requires precise adjustments of the structures to optimize the binding, what is possible due to the intrinsic flexibility of biological macromolecules, but very difficult to follow using static pictures of those structures. Although some information about flexibility and induced fit could be extracted from the set of conformations available in PDB, onty theoretical methods can draw a full picture of the phenomenon. A series of tools and databases related to flexibility have been developed to offer an integrated approach to study flexibility.

NAFlex (Nucleic Acid Flexibility). Web tool to study the flexibility of nucleic acids, either isolated or bound to other molecules. The server offers a variety of methods to explore nucleic acid flexibility, from coarse-grained low resolution mesoscopic models to atomistic molecular dynamics simulations. Trajectories obtained, or imported externally, can be visualized and analyzed using a large number of tools.

Reference:
Adam Hospital, Ignacio Faustino, Rosana Collepardo-Guevara, Carlos González, Josep Lluís Gelpí, Modesto Orozco.
NAFlex: A web server for the study of nucleic acid flexibility.
Nucleic Acids Research, 2013, Volume 41, Issue W1, 1 July 2013, Pages W47–W55.

BigNASim is a novel database system to store MD trajectories and analyses of nucleic acids. The initial data set available consists mainly on the benchmark of the new molecular dynamics force-field parmBSC1. The database is based on a combination of two NoSQL engines: Cassandra for storing trajectories and MongoDB to store analysis results and simulation metadata.

References:
Adam Hospital, Pau Andrio, Cesare Cugnasco, Laia Codo, Yolanda Becerra, Pablo D. Dans, Federica Battistini, Jordi Torres, Ramón Goñi, Modesto Orozco, Josep Lluís Gelpí.
BIGNASim: a NoSQL database structure and analysis portal for nucleic acids simulation data.
Nucleic Acids Research (2016) 44(D1), D272-D278.

Ivan Ivani, Pablo D. Dans, Agnès Noy, Alberto Pérez, Ignacio Faustino, Adam Hospital, Jürgen Walther, Pau Andrio, Ramon Goñi, Alexandra Balaceanu, Guillem Portella, Federica Battistini, Josep Lluís Gelpí, Carlos González, Michele Vendruscolo, Charles A. Laughton, Sarah A. Harris, David A. Case and Modesto Orozco.
ParmBSC1: A refined force field for DNA simulations.
Nature Methods (2016) 13(1), 55-58

MCDNA uses Monte Carlo sampling to obtain a set of representative DNA conformations at base pair step level accuracy.
MCDNAlite takes advantage of the extended next-to-nearest neighbor (enNN) model to provide the user a limited number of alternative equilibrium B-DNA conformations according to the tetrameric states of the underlying sequence.

Reference:
Jürgen Walther, Pablo D Dans, Alexandra Balaceanu, Adam Hospital, Genís Bayarri, Modesto Orozco
A multi-modal coarse grained model of DNA flexibility mappable to the atomistic level
Nucleic Acids Research (2020). gkaa015.

miniABC is a multi-laboratory effort to describe the structural and dynamical properties of duplex B-DNA under physiological conditions.

Reference:
Pablo D Dans, Alexandra Balaceanu, Marco Pasi, Alessandro S Patelli, Daiva Petkevičiūtė, Jürgen Walther, Adam Hospital, Genís Bayarri, Richard Lavery, John H Maddocks, Modesto Orozco
The static and dynamic structural heterogeneities of B-DNA: extending Calladine–Dickerson rules
Nucleic Acids Research (2019). Volume 47, Issue 21, 02 December 2019, Pages 11090–11102.

Nucleosome Dynamics plays a major role in transcriptional regulation and most DNA-related processes.

Reference:
Diana Buitrago, Laia Codó, Ricard Illa, Pau de Jorge, Federica Battistini, Oscar Flores, Genis Bayarri, Romina Royo, Marc Del Pino, Simon Heath, Adam Hospital, Josep Lluís Gelpí, Isabelle Brun Heath, Modesto Orozco
Nucleosome Dynamics: a new tool for the dynamic analysis of nucleosome positioning
Nucleic Acids Research (2019). Volume 47, Issue 18, 10 October 2019, Pages 9511–9523.

MoDEL (Molecular Dynamics Extended Library) is a database holding over 1,800 trajectories ranging from 10 ns to 1ms in length, from a representative set of protein structures.

Reference:
Tim Meyer, Marco D'Abramo, Adam Hospital, Manuel Rueda, Carles Ferrer-Costa, Alberto Pérez, Oliver Carrillo, Jordi Camps, Carles Fenollosa, Dmitry Repchevsky, Josep Lluís Gelpí, Modesto Orozco.
MoDEL (Molecular Dynamics Extended Library): a database of atomistic molecular dynamics trajectories.
Structure. (2010) 18(11), 1399-1409.

MDdMD. Web portal to analyze large scale conformational changes in proteins, through Discrete Dynamics simulations and Normal Mode analysis.

Reference:
Pedro Sfriso, Agusti Emperador, Laura Orellana, Adam Hospital, Josep Lluis Gelpi and Modesto Orozco.
Finding conformational pathways from discrete molecular dynamics simulations.
J. Chem. Theory Comput., 2012, 8(11): 4707-4718.

GOdMD is a new method for determining pathways for conformational transitions in macromolecules based on the use of discrete molecular dynamics and biasing techniques using a combination of essential dynamics and Maxwell-Demon sampling techniques.

Reference:
Pedro Sfriso, Adam Hospital, Agustí Emperador, Modesto Orozco.
Exploration of Conformational Transition Pathways from Coarse-Grained Simulations.
Bioinformatics. (2013) Advance Access.

TransAtlas is a comprehensive database of protein conformational transitions containing 64646 independent transitions obtained from the analysis of 750K conformational transitions (more than 7.5 M intermediate structures) covering the entire proteome. Atomistic models of intermediate structures over the transition path are reconstructed to be used as starting point in higher-level computations (MD).
FlexServ. Web portal for the analysis of flexibility including the generation of coarse-grained molecular dynamics trajectories, analysis of essential dynamics, BFactors, hinge points and flexibility correlations.

Reference:
Jordi Camps, Oliver Carrillo, Agustí Emperador, Laura Orellana, Adam Hospital, Manuel Rueda, Damjan Cicin-Sain, Marco D'Abramo, Josep Lluís Gelpí, Modesto Orozco.
FlexServ: An integrated tool for the analysis of protein flexibility.
Bioinformatics. (2009) 25(13), 1709-1710.

MoDEL-CNS is a platform designed to provide web-access to atomistic-MD trajectories for relevant signal transduction proteins.

Reference:
https://mmb.irbbarcelona.org/MoDEL-CNS/#/

BioExcel-CV19 is a platform designed to provide web-access to atomistic-MD trajectories for macromolecules involved in the COVID-19 disease. The project is part of the open access initiatives promoted by the world-wide scientific community to share information about COVID-19 research. BioExcel-CV19 web server interface presents the resulting trajectories, with a set of quality control analyses and system information. All data produced by the project is available to download from an associated programmatic access API.

Reference:
https://bioexcel-cv19.bsc.es/#/

Protein Data Bank. Mirror to the central repository for experimental 3D structures.
MDWeb & MDMoby. A comprehensive set of tools to allow automated setup and analysis of molecular dynamics trajectories. Access is available through a Web portal, but also through a series of web-services developed in the Biomoby framework

Reference:
Adam Hospital, Pau Andrio, Carles Fenollosa, Damjan Cicin-Sain, Modesto Orozco, Josep Lluís Gelpí
MDWeb and MDMoby: an integrated web-based platform for molecular dynamics simulations.
Bioinformatics, 2012, 28(9):1278-1279.

BioExcel Building Blocks is a software library for interoperable biomolecular simulation workflows.

Reference:
Pau Andrio, Adam Hospital, Javier Conejero, Luis Jordá, Marc Del Pino, Laia Codo, Stian Soiland-Reyes, Carole Goble, Daniele Lezzi, Rosa M. Badia, Modesto Orozco & Josep Ll. Gelpi
BioExcel Building Blocks, a software library for interoperable biomolecular simulation workflows.
Nature Scientific Data (2019), 6, Article number: 169.

The BioBB REST API provides programmatic access to the list of >150 available tools integrated in the BioBB library without the need for any local installation. The website contains extensive information about the endpoints, including documentation and tutorials.

Reference:
Genís Bayarri, Pau Andrio, Adam Hospital, Modesto Orozco & Josep Lluís Gelpí.
BioExcel Building Blocks REST API (BioBB REST API), programmatic access to interoperable biomolecular simulation tools.
Bioinformatics Application Note (minor revisions), 2022.

The BioBB Workflows web server is a web-based graphical user interface (GUI) offering access to a collection of transversal pre-configured biomolecular simulation workflows assembled with the BioExcel Building Blocks library. Available workflows include Molecular Dynamics setup, protein-ligand docking, trajectory analyses and small molecule parameterization. Workflows can be launched in the platform or downloaded to be run in the users’ own premises. Remote launching of long executions to user’s available High-Performance computers is possible, only requiring configuration of the appropriate access credentials. The web-based graphical user interface offers a high level of interactivity, with integration with the NGL viewer to visualize and check 3D structures, MDsrv to visualize trajectories, and Plotly to explore 2D plots.

Reference:
Genís Bayarri, Pau Andrio, Adam Hospital, Modesto Orozco & Josep Lluís Gelpí
BioExcel Building Blocks Workflows (BioBB-Wfs), an integrated web-based platform for biomolecular simulations.
Nucleic Acids Research, Web Server Issue (just accepted), 2022.

3D Representation Sharing (3dRS) is a web-based tool designed to share biomolecular structure representations, including 4D ensembles derived from Molecular Dynamics (MD) trajectories. The server offers a team working in different locations a single URL to share and discuss structural data in an interactive fashion, with the possibility to use it as a live figure for scientific papers.

Reference:
Genís Bayarri, Adam Hospital and Modesto Orozco.
3dRS, a Web-Based Tool to Share Interactive Representations of 3D Biomolecular Structures and Molecular Dynamics Trajectories.
Front. Mol. Biosci., 13 August 2021, doi: 10.3389/fmolb.2021.726232.

Molywood is a robust and intuitive tool that builds on the capabilities of Visual Molecular Dynamics (VMD) to automate all stages of macromolecular structure and trajectories movie rendering. Based on Python scripts, it implements the basic concepts of actions, layers, grids and concurrency and requires no programming experience to run. Extensive documentation, including examples and tutorials, can be found in the website.

Reference:
Miłosz Wieczór, Adam Hospital, Genís Bayarri, Jacek Czub and Modesto Orozco.
Molywood: streamlining the design and rendering of molecular movies.
Bioinformatics, Volume 36, Issue 17, 1 September 2020, Pages 4660–4661, https://doi.org/10.1093/bioinformatics/btaa584

References:

Agustí Emperador, Tim Meyer, Modesto Orozco.
Protein flexibility from discrete molecular dynamics simulations using quasi-physical potentials.
Proteins. 2010 78(1):83-94.

Modesto Orozco, Laura Orellana, Adam Hospital, Athi Naganathan, Agustí Emperador, Oliver Carrillo, Josep Lluís Gelpí
Coarse-grained representation of protein flexibility. Foundations, successes, and shortcomings.
Adv. Protein Chem. Struct. Biol. 2011;85:183-215.

Laia Codó, Genís Bayarri, Javier Alvarez Cid-Fuentes, Javier Conejero, Adam Hospital, Romina Royo, Dmitry Repchevsky, Marco Pasi, Athina Meletiou, Mark D. McDowall, Fatima Reham, José A. Alcantara, Brian Jimenez-Garcia, Jürgen Walther, Ricard Illa, François Serra, Michael Goodstadt, David Castillo, Satish Sati, Diana Buitrago, Isabelle Brun-Heath, Juan Fernandez-Recio, Giacomo Cavalli, Marc Marti-Renom, Andrew Yates, Charles A. Laughton, Rosa M. Badia, Modesto Orozco, Josep Ll. Gelpí
MuGVRE. A virtual research environment for 3D/4D genomics
bioRxiv (2019)