Research Article LoopX: A Graphical User Interface-Based Database for Comprehensive Analysis and Comparative Evaluation of Loops from Protein Structures RAJASHEKAR VARMA KADUMURI and RAMAKRISHNA VADREVU ABSTRACT Due to their crucial role in function, folding, and stability, protein loops are being targeted for grafting/designing to create novel or alter existing functionality and improve stability and foldability. With a view to facilitate a thorough analysis and effectual search options for extracting and comparing loops for sequence and structural compatibility, we developed, LoopX a comprehensively compiled library of sequence and conformational features of *700,000 loops from protein structures. The database equipped with a graphical user interface is empowered with diverse query tools and search algorithms, with various ren- dering options to visualize the sequence- and structural-level information along with hy- drogen bonding patterns, backbone /, w dihedral angles of both the target and candidate loops. Two new features (i) conservation of the polar/nonpolar environment and (ii) con- servation of sequence and conformation of specific residues within the loops have also been incorporated in the search and retrieval of compatible loops for a chosen target loop. Thus, the LoopX server not only serves as a database and visualization tool for sequence and structural analysis of protein loops but also aids in extracting and comparing candidate loops for a given target loop based on user-defined search options. Keywords: data mining, database, loop engineering/grafting, protein loops, web-based GUI. 1. INTRODUCTION L oops, the regions that connect secondary structure elements, constitute the key components of protein function (Fetrow, 1995; Fiser et al., 2000). In addition, they also play a major role in protein stability and folding (Marcelino and Gierasch, 2008; Fu et al., 2009; Lewandowska et al., 2010; Balasco et al., 2013). The design of novel functions in proteins with increased stability has been a long-standing goal in the field of protein engineering. Recently, experimental endeavors indicate that grafting/engineering of loop regions in protein scaffolds can lead to novel activity and can alter existing functionality (Park et al., 2006; Ochoa-Leyva et al., 2009; Walser et al., 2012) of enzymes. In addition, the strategy of swapping loops/ turns has also been exploited to enhance protein stability and foldability (Binz et al., 2005; Tawfik, 2006; Fu et al., 2009; Ochoa-Leyva et al., 2009; Walser et al., 2012; Wijma et al., 2013). Department of Biological Sciences, Birla Institute of Technology & Science-Pilani, Hyderabad, India. Availability: LoopX is currently available at http://182.75.45.10/loopx/loopx.html JOURNAL OF COMPUTATIONAL BIOLOGY Volume 24, Number 0, 2017 # Mary Ann Liebert, Inc. Pp. 1–7 DOI: 10.1089/cmb.2016.0197 1