xMoDEL: Molecular Dynamics Libraries
Molecular Dynamic simulation is a theoretical technique that is currently extensively used to derive macromolecular structure flexibility properties. Due to recent developments of more efficient simulations engines and the use of High Performance Computer (HPC) systems, a fourth dimension (time) can be computed for a large set of macromolecules, in a High Throughput (HT) approach.
- MoDEL: Molecular Dynamics Extended Library:
More than 1700 trajectories of proteins representative of monomeric soluble structures in the protein data bank (PDB) have been obtained by means of state-of-the-art atomistic molecular dynamics simulations in near-physiological conditions. The trajectories and analyses are stored in a large data warehouse, which can be queried for dynamic information on proteins, including interactions. Here, we describe the project and the structure and contents of our database, and provide examples of how it can be used to describe the global flexibility properties of proteins. Basic analyses and trajectories stripped of solvent molecules at a reduced resolution level are available from our web server.
From the original MoDEL database, a set of interesting simulation libraries have been derived and extended:
- nMoDEL (nanoMoDEL): Five selected proteins representatives of the three CATH major classes: 1cqy, 1kte and 1opc, and two proteins for which very large amount of experimental information on flexibility is available: 1ubq and 2gb1 were chosen to built an ultrasmall dataset for validation purposes. Simulations were run up to 1 microsecond.
- µMoDEL (microMoDEL): 30 structures representing all metafolds were simulated with 4 different forcefields (parm99, CHARMM-98, GROMOS-96 and OPLS-AA) and with a simulation time up to 100ns.
- kMoDEL (kinoMoDEL): DB in construction that tries to cover all the different protein kinases described in the PDB, as well as a number of modelled structures, wherever possible. Both apo- and holo- forms are simulated if exist. Protein kinases are one of the main cytoplasmic targets for drugs and are systems where their flexibility properties are crucial.
- pMoDEL (pharmaMoDEL): DB in construction that tries to cover all the different target proteins of pharmacological interest. Both protein apo- and holo- forms are considered. Modelled structures (only where there is a high sequence identity) are also used,