Impressive advances in the applications of bioinformatics for protein structure prediction coupled with growing structural databases on one hand and the insurmountable time-scale problem with ab initio computational methods on the other continue to raise doubts whether a computational solution to the protein folding problem—categorized as an NP-hard problem—is within reach in the near future. Combining some specially designed biophysical filters and vector algebra tools with ab initio methods, we present here a promising computational pathway for bracketing native-like structures of small alpha helical globular proteins departing from secondary structural information. The automated protocol is initiated by generating multiple structures around the loops between secondary structural elements. A set of knowledge-based biophysical filters namely persistence length and radius of gyration, developed and calibrated on approximately 1000 globular proteins, is introduced to screen the trial structures to filter out improbable candidates for the native and reduce the size of the library of probable structures. The ensemble so generated encompasses a few structures with native-like topology. Monte Carlo optimizations of the loop dihedrals are then carried out to remove steric clashes. The resultant structures are energy minimized and ranked according to a scoring function tested previously on a series of decoy sets vis-à-vis their corresponding natives. We find that the 100 lowest energy structures culled from the ensemble of energy optimized trial structures comprise at least a few to within 3–5 Å of the native. Thus the formidable “needle in a haystack” problem is narrowed down to finding an optimal solution amongst a computationally tractable number of alternatives. Encouraging results obtained on twelve small alpha helical globular proteins with the above outlined pathway are presented and discussed.