Modeling Structures and Motions of Loops in Protein Molecules

Authors to whom correspondence should be addressed; E-Mails: amarda@gmu.edu (A.S.);kavraki@rice.edu (L.E.K.); Tel.: +1-703-993-4135 (A.S.); Fax: +1-703-993-1710 (A.S.);Tel.: +1-713-348-5737 (L.E.K.); Fax: +1-713-348-5930 (L.E.K.)Received: 26 December 2011; in revised form: 10 January 2012 / Accepted: 3 February 2012 /Published: 13 February 2012Abstract: Unlike the secondary structure elements that connect in protein structures, loopfragments in protein chains are often highly mobile even in generally stable proteins. Thestructural variability of loops is often at the center of a protein’s stability, folding, and evenbiological function. Loops are found to mediate important biological processes, such assignaling, protein-ligand binding, and protein-protein interactions. Modeling conformationsof a loop under physiological conditions remains an open problem in computational biology.This article reviews computational research in loop modeling, highlighting progress andchallenges. Important insight is obtained on potential directions for future research.Keywords: loop modeling; conformational ensemble; equilibrium fluctuations; native state;structural analysis of proteins; structural bioinformatics