Random Coordinate Descent with Spinor-matrices and Geometric Filters for Efficient Loop Closure.

Abstract

Protein loop closure constitutes a critical step in loop and protein modeling whereby geometrically feasible loops must be found between two given anchor residues. Here, a new analytic/iterative algorithm denoted random coordinate descent (RCD) to perform protein loop closure is described. The algorithm solves loop closure through minimization as in cyclic coordinate descent but selects bonds for optimization randomly, updates loop conformations by spinor-matrices, performs loop closure in both chain directions, and uses a set of geometric filters to yield efficient conformational sampling. Geometric filters allow one to detect clashes and constrain dihedral angles on the fly. The RCD algorithm is at least comparable to state of the art loop closure algorithms due to an excellent balance between efficiency and intrinsic sampling capability. Furthermore, its efficiency allows one to improve conformational sampling by increasing the sampling number without much penalty. Overall, RCD turns out to be accurate, fast, robust, and applicable over a wide range of loop lengths. Because of the versatility of RCD, it is a solid alternative for integration with current loop modeling strategies.