A divide and conquer approach to fast loop modeling

Abstract

We describe a fast ab initio method for modeling local segments in protein structures. The algorithm is based on a divide and conquer approach and uses a database of precalculated look-up tables, which represent a large set of possible conformations for loop segments of variable length. The target loop is recursively decomposed until the resulting conformations are small enough to be compiled analytically. The algorithm, which is not restricted to any specific loop length, generates a ranked set of loop conformations in 20-180 s on a desktop PC. The prediction quality is evaluated in terms of global RMSD. Depending on loop length the top prediction varies between 1.06 A RMSD for three-residue loops and 3.72 A RMSD for eight-residue loops. Due to its speed the method may also be useful to generate alternative starting conformations for complex simulations.

Cardiomyopathy in patients with POMT1-related congenital and limb-girdle muscular dystrophy

“…The secondary structure was analyzed with the consensus method, 22 while disordered regions were searched with SPRITZ 23 and transmembrane helices predicted with TOPCONS. 24 The structure of the MIR domains (found in Mannosyltransferases, Inositol triphosphate receptors and Ryanodin receptors) was modeled with HOMER (URL: http://protein.bio.unipd.it/homer/) from the template structure with PDB code 1T9F previously identified with PSI-BLAST, with loops positioned using a fast divide and conquer approach 25 and the final model being evaluated with FRST. 26 The structure was visualized Abbreviations: CMD-MR, congenital muscular dystrophy with mental retardation; LGMD-MR, limb-girdle muscular dystrophy with mental retardation; LGMD-NOMR, LGMD with no mental retardation; MR, mental retardation; MRI, magnetic resonance imaging; POMT1, protein-o-mannosyltransferase 1.…”

Electric dipole reorientation in the interaction of botulinum neurotoxins with neuronal membranes

“…The models were generated by comparative modelling using the HOMER server (http://protein.bio.unipd.it/homer/). Loops and side chains were modelled with a fast divide and conquer method [43] and SCWRL [44], respectively. Structural alignments between the X-ray crystallographic structures of all toxin serotype L chains and the models were computed using CE [45] in order to validate the models.…”

Efficient Algorithms to Explore Conformation Spaces of Flexible Protein Loops

“…Some sampling procedures try to sample conformations using libraries of fragments obtained from previously solved structures [10], [20], [26], [28]. For example, a divide and conquer approach is described in [26] that generates a database of fragments of different residue lengths and types, by using a Ramachandran plot distribution.…”

“…For example, a divide and conquer approach is described in [26] that generates a database of fragments of different residue lengths and types, by using a Ramachandran plot distribution. These fragments are then concatenated to build conformations of a longer loop.…”