Editing Protein engineering (section)

===Structural prediction===
''De novo'' generation of protein benefits from knowledge of existing protein structures. This knowledge of existing protein structure assists with the prediction of new protein structures. Methods for protein structure prediction fall under one of the four following classes:  ''ab initio,'' fragment based methods, homology modeling, and protein threading.<ref name=PoluriBook/>{{page needed|date=May 2017}}

====''Ab initio''====
These methods involve free modeling without using any structural information about the template. ''Ab initio'' methods are aimed at prediction of the native structures of proteins corresponding to the global minimum of its free energy. some examples of ''ab initio'' methods are AMBER, GROMOS, GROMACS, CHARMM, OPLS, and ENCEPP12. General steps for  ''ab initio'' methods begin with the geometric representation of the protein of interest. Next, a potential energy function model for the protein is developed. This model can be created using either molecular mechanics potentials or protein structure derived potential functions. Following the development of a potential model, energy search techniques including molecular dynamic simulations, Monte Carlo simulations and genetic algorithms are applied to the protein.<ref name=PoluriBook/>{{page needed|date=May 2017}}

====Fragment based====
These methods use database information regarding structures to match homologous structures to the created protein sequences. These homologous structures are assembled to give compact structures using scoring and optimization procedures, with the goal of achieving the lowest potential energy score. Webservers for fragment information are I-TASSER, ROSETTA, ROSETTA @ home, FRAGFOLD, CABS fold, PROFESY, CREF, QUARK, UNDERTAKER, HMM, and ANGLOR.<ref name=PoluriBook/>{{rp|72}}

====Homology modeling====
These methods are based upon the homology of proteins. These methods are also known as comparative modeling. The first step in homology modeling is generally the identification of template sequences of known structure which are homologous to the query sequence. Next the query sequence is aligned to the template sequence. Following the alignment, the structurally conserved regions are modeled using the template structure. This is followed by the modeling of side chains and loops that are distinct from the template. Finally the modeled structure undergoes refinement and assessment of quality. Servers that are available for homology modeling data are listed here: SWISS MODEL, MODELLER, ReformAlign, PyMOD, TIP-STRUCTFAST, COMPASS, 3d-PSSM, SAMT02, SAMT99, HHPRED, FAGUE, 3D-JIGSAW, META-PP, ROSETTA, and I-TASSER.<ref name=PoluriBook/>{{page needed|date=May 2017}}

====Protein threading====
Protein threading can be used when a reliable homologue for the query sequence cannot be found. This method begins by obtaining a query sequence and a library of template structures. Next, the query sequence is threaded over known template structures. These candidate models are scored using scoring functions. These are scored based upon potential energy models of both query and template sequence. The match with the lowest potential energy model is then selected. Methods and servers for retrieving threading data and performing calculations are listed here: GenTHREADER, pGenTHREADER, pDomTHREADER, ORFEUS, PROSPECT, BioShell-Threading, FFASO3, RaptorX, HHPred, LOOPP server, Sparks-X, SEGMER, THREADER2, ESYPRED3D, LIBRA, TOPITS, RAPTOR, COTH, MUSTER.<ref name=PoluriBook/>{{page needed|date=May 2017}}

For more information on rational design see [[site-directed mutagenesis]].