Protein modelling and surface folding by limiting the degrees of freedom

Abstract

One aspect of tissue engineering represents modelling of the extracellular matrix of connective tissue as the fiber network arrangement of the matrix determines its tensile strength. In order to define the correct position of the e.g. collagen in a structure, an optimized tertiary structure must be characterized. Existing approaches of protein models consider random packing of rigid spheres. We propose an alternative strategy to model protein structure by focusing on the folding. Our model considers (a) segments of amino-acid peptides or beads, (b) hydrogen bond distances, and (c) the distance geometry as functional components rather than minimizing distances between the centers of atoms. We reduced the molecular volume by using concepts from low dimensional topology, such as braids and surfaces, via differential geometry. A braid group maintains the continuity of a sequence while the spatial minimization is performed, and guarantees the continuity during the process. We have applied this approach to different examples of known protein sequences using ab initio protocols of ProteoRubix Systems™. Sequence files of three different proteins types were tested and modeled by ProteoRubix™ and compared to models derived by other methods. ProteoRubix™ created near-identical models with minimal computational load. This model can be expanded to large, multi-molecular network structures.