The CECAM CALL for workshops and schools that will run from April 2019 to March 2020 is now open! The text for the call and information on how to submit a proposal can be found at https://www.cecam.org/submitting.html. Deadline for submissions is 16 July 2018.
Good luck!
Contacts can be an important tool for defining (meta)stable states in processes involving biomolecules. For example, an analysis of contacts can be particularly useful when defining bound states during a binding processes between proteins, DNA, and small molecules (such as potential drugs).
The contacts analyzed by the contact_map package can be either intermolecular or intramolecular, and can be analyzed on a residue-residue basis or an atom-atom basis.
This package makes it very easy to answer questions like:
It also facilitates visualization of the contact matrix, with colors representing the fraction of trajectory time that the contact was present. Full documentation available at http://contact-map.readthedocs.io/.
Information about software installation, testing and a link to the source code, can be found in our E-CAM software Library here.
The practical application of this software module is the pilot project in collaboration with BiKi Technologies on “Binding Kinetics“, sustained by an E-CAM postdoctoral researcher at University of Amsterdam. The project aims at investigating the binding/unbinding of a selective reversible inhibitor for protein GSK3β.
Contacts between a ligand and a protein are an excellent way to characterize “hotspots” – states where the ligand stays for a significant amount of time, but not nearly as long as in the final binding pocket. These hotspots are metastable states in path sampling, and should be treated with a multiple state approach. Therefore, attempting to identify those states would be a necessarily preliminary step to prepare the path sampling simulation.
Other more general applications to this module include protein-protein aggregation or DNA-protein binding, as well as large scale conformational changes in biomolecules, such as protein folding.
The scientific reports* from the following workshops conducted in year 2 of the project E-CAM (2017):
are now available for download on our website at this location. Furthermore, they will also integrate the CECAM Report of Activities 2017, published every year on the website www.cecam.org.
Each report includes:
*© CECAM 2017, all rights reserved.
Please address any comments or questions to info@e-cam2020.eu.
As technologies reach atomic length and energy scales, the simulation of quantum effects acquires practical interest beyond basic science in areas ranging from sustainable energy, to medicine, to quantum computing. Brute force simulation of quantum dynamical properties, however, is currently out of reach due to the exponential scaling of its cost with the system size, and the development of approximate methods is an active field that must be coupled with the development of highly effective software to reach the computational capacity necessary to target significant applications. The goal of E-CAM’s Work-package 3 “Quantum Dynamics” (WP3) is to develop software to contribute to this effort by implementing relevant algorithms and fostering the transition from in-house codes to reliable, modular, scalable and well documented community packages.
In this report, we first review current algorithms for the simulation of quantum dynamics, focusing in particular on approximate schemes that achieve satisfactory accuracy with manageable numerical cost and have good potential for massively parallel implementations. We then discuss software packages that make these methods available, focusing in particular on codes that enable to interface quantum dynamical algorithms with ab initio evaluation of the interactions in the system. Finally, we give an overview of the software modules to be developed within WP3 of E-CAM.
The database of the force fields developed by the SNS SMART group (SNS, Pisa, Italy), including the metal-ions force fields optimized within E-CAM using novel Machine Learning procedure (reported in a recent publication[1] and in a case study reported by E-CAM here), are now available for download at http://smart.sns.it/vmd_molecules/.
[1] Francesco Fracchia, Gianluca Del Frate, Giordano Mancini, Walter Rocchia, and Vincenzo Barone, Force Field Parametrization of Metal Ions from Statistical Learning Techniques, J. Chem. Theory Comput. 2018, 14, 255−273 DOI: 10.1021/acs.jctc.7b00779
One quarter to one third of all proteins require metals to function but the description of metal ions in standard force fields is still quite primitive. In this case study and interview an E-CAM project to develop a suitable parameterisation using machine learning is described. The training scheme combines classical simulation with electronic structure calculations to produce a force field comprising standard classical force fields with additional terms for the metal ion-water and metal ion-protein interactions. The approach allows simulations to run as fast as standard molecular dynamics codes, and is suitable for efficient massive parallelism scale-up.
The power of advanced simulation combined with statistical theory , experimental know-how and high performance computing is used to design a protein based molecular switch sensor with remarkable sensitivity and significant industry potential. The sensor technology has applications across commercial markets including diagnostics, immuno-chemistry, and therapeutics.
The publication “Probing spatial locality in ionic liquids with the grand canonical adaptive resolution molecular dynamics technique (GC-AdResS)“ by the Theoretical and Mathematical Physics in Molecular Simulation group of the Freie Universität Berlin, lead by Prof.Luigi Delle Site, E-CAM partner, describes the use of the GC-AdResS molecular dynamics technique to test the spatial locality of the ionic liquid 1-ethyl 3-methyl imidazolium chloride liquid. The main aspect of GC-AdResS is the possibility to couple two simulation boxes together and combine the advantages of classical atomistic simulations with those from coarse gained simulations.
The publication post-print version is open access and can be downloaded directly from the Zenodo repository here. The publisher AIP version can be found at http://aip.scitation.org/doi/10.1063/1.5009066.
E-CAM currently runs a pilot project on the development of the GC-AdResS scheme and one of its goals is to develop a library or recipe with which GC-AdResS can be implemented in any MD Code. The current focus is to adjust the implemented version of GC-AdResS in GROMACS. The long-term goal of this project is to promote and stimulate the community to use it as a tool for multiscale simulations and analysis. More information about this pilot project can be found here.
Title: Probing spatial locality in ionic liquids with the grand canonical adaptive resolution molecular dynamics technique
Authors: B. Shadrack Jabes, C. Krekeler, R. Klein and L. Delle Site
Abstract: We employ the Grand Canonical Adaptive Resolution Simulation (GC-AdResS) molecular dynamics technique to test the spatial locality of the 1-ethyl 3-methyl imidazolium chloride liquid. In GC-AdResS, atomistic details are kept only in an open sub-region of the system while the environment is treated at coarse-grained level; thus, if spatial quantities calculated in such a sub-region agree with the equivalent quantities calculated in a full atomistic simulation, then the atomistic degrees of freedom outside the sub-region play a negligible role. The size of the sub-region fixes the degree of spatial locality of a certain quantity. We show that even for sub-regions whose radius corresponds to the size of a few molecules, spatial properties are reasonably reproduced thus suggesting a higher degree of spatial locality, a hypothesis put forward also by other researchers and that seems to play an important role for the characterization of fundamental properties of a large class of ionic liquids.
