The Interval Branch-And-Prune Algorithm For The Protein Structure Determination

A general trend of structural biology is the switch of a rigid description of protein structures, as in the first X-ray structures in the 50u0027s, to a flexible description, in which each protein populate several distinct conformations or even a continuum of conformations. This flexibility was shown in numerous cases to have a crucial importance in the function of proteins. Most of the methods for bio-molecular structure calculations are, up to now, based on a combination of sampling and optimization, which does not allow a systematic exploration of the conformational space. But, in the case of highly flexible bio-molecules, a systematic (or global) exploration of the conformational space would be very welcome.On the other hand, the interval branch-and-prune (iBP) approach has been proposed as a method for allowing a global optimization of molecular structure under distance restraints, the so-called Distance Geometry problem. A recursive implementation of this algorithm has permitted to apply this approach on small structures of proteins in alpha-bundles for which few long-range distance restraints were known. Here, we are going to present the results obtained on a set of protein structures with sizes from 24 to 100 residues, displaying various secondary structures and topology. The distance restraints present on these structures were chosen to contain exclusively short-range information.The results obtained with various sets of distance restraints, including exact values and interval of values, will be presented, in order to experimentally evaluate the complexity of the algorithm on real-case of protein structure determination. Several procedures of acceleration will be used in order to allow a complete exploration of the tree describing the molecular Distance Geometry problem. The efficiency of the exploration will be evaluated using the self-organizing map (SOM) clustering approach, and the quality of obtained conformations with respect to Ramachandran plots and steric clashes will be evaluated.References:Cassioli A, Bardiaux B, Bouvier G, Mucherino A, Alves R, Liberti L, Nilges M, Lavor C and Malliavin TE. An algorithm to enumerate all possible protein conformations verifying a set of distance constraints. BMC Bioinformatics, 28;16:23 (2015).Lavor C., Alves R., Figueiredo W., Petraglia A., Maculan N. Clifford Algebra and the Discretizable Molecular Distance Geometry Problem. Adv. Appl. Clifford Algebras 25 (2015), 925-942.