Computational tools for protein modeling

Protein modeling is playing a more and more important role in protein and peptide sciences due to improvements in modeling methods, advances in computer technology, and the huge amount of biological data becoming available. Modeling tools can often predict the structure and shed some light on the function and its underlying mechanism. They can also provide insight to design experiments and suggest possible leads for drug design. This review attempts to provide a comprehensive introduction to major computer programs, especially on-line servers, for protein modeling. The review covers the following aspects: (1) protein sequence comparison, including sequence alignment/search, sequence-based protein family classification, domain parsing, and phylogenetic classification; (2) sequence annotation, including annotation/prediction of hydrophobic profiles, transmembrane regions, active sites, signaling sites, and secondary structures; (3) protein structure analysis, including visualization, geometry analysis, structure comparison/classification, dynamics, and electrostatics; (4) three-dimensional structure prediction, including homology modeling, fold recognition using threading, ab initio prediction, and docking. We will address what a user can expect from the computer tools in terms of their strengths and limitations. We will also discuss the major challenges and the future trends in the field. A collection of the links of tools can be found at http://compbio.ornl.gov/structure/resource/.