Interactive simulation and visualisation to characterize Macromolecular structures and interactions UNITYMOL DOCKING,OPEP NORMAUX,HiRE-RNA LIBRE,PTOOLS,ABF GROS-GRAIN,ICMD,MAXDo VMOD,BioSpring, ECHANTILLONNAGE,ProPHet,ExaViz Entropie,DeltaG,Pep-Fold2,FlexBase, Marc Baaden, CNRS UPR 9080 / IBPC
0111010100010010100101101110010101000010101111101010111010101001011110101000100111110000101110001101100011100100001111010010101 0111010100010010100101101110010101010111010101001011110101000100111110000101110001101100011100100001111010010101101000010101111 Laboratory of Theoretical Biochemistry 0101001011110101000100111110000011101010001001010010110111001010100001010111110101011101101110001101100011100100001111010010101 0111010100010010100101101110010101000010101111101010111010101001011110101000100111110000101110001101100011100100001111010010101 0111010100010010100101101110010101000010101111100100111110000101110001101101011101010100101111010100100011100100001111010010101 CNRS UPR 9080 Research directions
Looking inside the cell: a variety of topics The nucleic-acid lovers homologeous recombination: RecA/DNA DNA flexibility/assembly Chantal Alexey
Looking inside the cell: a variety of topics Those who care about protein stability Fabio Guillaume mechanical stability how local mechanics relates to protein properties and reactivity thermophilicity Sophie
Looking inside the cell: a variety of topics They study protein love stories conformational changes upon protein-protein interactions Charles peptide - α , β tubulin interaction Chantal Sophie
Pushing the limits: towards mesoscopic simulations They simulate the cell cytoplasm effect of hydrodynamic interactions Fabio Philippe They look at mitochondrial membrane fusion Antoine Jérôme Marc
The neuron: degenerative diseases, synapses Amyloid aggregation Phuong Philippe Fabio Pentameric ligand-gated channels in synapses Jérôme Marc Antoine
Toward more efficient simulation approaches development of sophisticated “coarse-grain” representations OPEP proteins Phuong Fabio Philippe Sophie HiRE DNA/RNA MUPHY : toward simulating the cytoplasm guiding simulations, making them faster: enhanced sampling Jérôme Fabio Charles Guillaume
Toward more efficient simulation approaches How to generate a trajectory? (we try not to generate random numbers) development of sophisticated “coarse-grain” representations OPEP proteins Phuong Fabio Philippe Sophie HiRE DNA/RNA MUPHY : toward simulating the cytoplasm guiding simulations, making them faster: enhanced sampling Jérôme Fabio Charles Guillaume
Sampling and analyzing high dimensional configurational spaces Courtesy J. Cortés Charles Robert and Frédéric Cazals (Inria) ● Global optimization method: hybridize two strategies 1) T-RRT: Voronoï bias (taboo-ish) + Rapidly-expanding Random Tree with Temperature control Jaillet, Corcho, Pérez & Cortés (2011) J Comp Chem + 2) Monte Carlo with minimization (Basin Hopping) Li & Scheraga (1987) PNAS Synergy: exploration Number of new low-energy and minima found exploitation Mo More basin- Hybrid algorithm: T-RRT + BH threads Mo More T-R -RRT-l -like ke hopping-like ● Targets: frustrated, multifunnel macromolecular systems (here BLN69 beta-barrel model system) – Cazals et al (2015) J Comp Chem ● Energy Landscape analysis and comparison methods Roth et al (2016) J Comp Chem 9
Toward more efficient simulation approaches What to do with all these numbers? high-level visualization and user interaction innovative education approaches Marc Antoine projection onto relevant reaction coordinates � ~ everyone... i =1 ,. . . → ~ X i R
0111010100010010100101101110010101000010101111101010111010101001011110101000100111110000101110001101100011100100001111010010101 A few software developments.. 1100011100100001111010010101011101010001001010010110111001010100001010111110101011101010100101111010100010011111000010111000110 110001110010000111101001010101111100001011100011011000111001000011110100101011100011100100001111010010101011101010001001010010110 011111000010111000110110001110010000111101001010111000111001000011110100101010111010100010010100101101110010101000010101111101011 1100011100100001111010010101011101010001001010010110111001010100001010111110101011101010100101111010100010011111000010111000110 Nom Auteur Objectif Distribution Dissémination MB réseau élastique augmenté interactif (interne) ... BioSpring SP , PhD reconstruction acides nucléiques interne CG-FA JH biais sur variables collectives en MD licence libre colvars module NAMD, LAMMPS CHR analyse des complexes protéiques (interne) ... FlexBase MB laboratoire virtuel licence libre FvNano SP , PhD modèle GG acides nuc. (ARN+ADN) interne HiRe-RNA MB visualisation moléculaire sur GPU licence libre HyperBalls AM MD en coordonnées internes sur demande ICMD SSM partenaires d'interactions protéiques MAXDo IBM WC GRID MB API pour simulations interactives licence libre MDDriver PhD prédiction de structures peptidiques web Pep-Fold2 SSM propriétés mécaniques de protéines sur demande ProPHet CP édition/manipulation de l'ADN (interne) ... PTools/ADN CP auto-assemblages par vissage (interne) ... PTools/Heligeom CP docking gros grains protéine/ADN licence libre PTools/PyAttract MB visualisation moléculaire et illustrative (interne) ... UnityMol CHR contrainte sur modes normaux VMOD CHARMM : : : : :
0111010100010010100101101110010101000010101111101010111010101001011110101000100111110000101110001101100011100100001111010010101 A few software developments.. 1100011100100001111010010101011101010001001010010110111001010100001010111110101011101010100101111010100010011111000010111000110 110001110010000111101001010101111100001011100011011000111001000011110100101011100011100100001111010010101011101010001001010010110 011111000010111000110110001110010000111101001010111000111001000011110100101010111010100010010100101101110010101000010101111101011 1100011100100001111010010101011101010001001010010110111001010100001010111110101011101010100101111010100010011111000010111000110 Nom Auteur Objectif Distribution Dissémination MB réseau élastique augmenté interactif (interne) ... BioSpring SP , PhD reconstruction acides nucléiques interne CG-FA JH biais sur variables collectives en MD licence libre colvars module NAMD, LAMMPS CHR analyse des complexes protéiques (interne) ... FlexBase MB laboratoire virtuel licence libre FvNano SP , PhD modèle GG acides nuc. (ARN+ADN) interne HiRe-RNA MB visualisation moléculaire sur GPU licence libre HyperBalls AM MD en coordonnées internes sur demande ICMD SSM partenaires d'interactions protéiques MAXDo IBM WC GRID MB API pour simulations interactives licence libre MDDriver PhD prédiction de structures peptidiques web Pep-Fold2 SSM propriétés mécaniques de protéines sur demande ProPHet CP édition/manipulation de l'ADN (interne) ... PTools/ADN CP auto-assemblages par vissage (interne) ... PTools/Heligeom CP docking gros grains protéine/ADN licence libre PTools/PyAttract MB visualisation moléculaire et illustrative (interne) ... UnityMol CHR contrainte sur modes normaux VMOD CHARMM : : : : :
tyrosine thymine coarse-grain/atomic resolution docking with ATTRACT w 1 + w 2 PTools w 3 w 8 w 4 Py/C++ library for Force fields w 7 w 5 w 6 macromolecule manipulation A TTRACT 1 flexible docking protein-protein https://github.com/ptools/ptools multi-copy/mean field method protein-DNA A TTRACT 2 Scorpion Development team [add your own…] Adrien Saladin Chantal Prévost Pierre Poulain Benjamin Boyer Benoist Laurent Martin Zacharias heligeom module Tâp Ha Duong Nathalie Basdevant Sébastien Fiorucci Saladin et al. BMC Struct Biol 2009 9:27
PTools applications PTools/docking applications ▻ mapping the interface : residues that best interact ▻ docking analysis : f NAT , f IR , i RMSD ▻ interfaces comparison PTools/Heligeom applications ▻ analysis ▻ construction Saladin et al. Nucleic Acids Res 2010 38:2313 ▻ prediction when coupled with docking axis (0,0,1) rotation angle 60.00 analysis translation 0.00 direction right-handed pitch 0.00 monomers/turn 6.00 construction 2 units of glutamine synthetase small interface binding mode variations discontinuities Boyer et al. PLoS ONE 2015 10 (3): e0116414
6 years 9500 downloads Texte • Full 3D development platform • Export to multiple platforms : • Advanced graphics engine OSX, Windows, Linux, Android, • Portable, intuitive to use iOS, .. WebGL .. • 3 languages : C#, Boo, Javascript Lv et al., PLoS ONE, 2013
Immersion Interactive simulation and visualisation
Immersion • be an actor and "manipulate" molecules (or data in general) • for example «serious games» such as FoldIt • immersion into the structural world of molecules • view in 3 dimensions • apprehend spatial architecture
Recommend
More recommend
