Structural Prediction Protein engineering

1 structural prediction

1.1 ab initio
1.2 fragment based
1.3 homology modeling
1.4 protein threading

structural prediction

de novo synthesis of protein benefits knowledge of existing protein structures. knowledge of existing protein structure assists prediction of new protein structures. methods protein structure prediction fall under 1 of 4 following classes: ab initio, fragment based methods, homology modeling, , protein threading.

ab initio

these methods involve free modeling without using structural information template. ab initio methods aimed @ prediction of native structures of proteins corresponding global minimum of free energy. examples of ab initio methods amber, gromos, gromacs, charmm, opls, , encepp12. general steps ab initio methods begin geometric representation of protein of interest. next, potential energy function model protein developed. model can created using either molecular mechanics potentials or protein structure derived potential functions. following development of potential model, energy search techniques including molecular dynamic simulations, monte carlo simulations , genetic algorithms applied protein.

fragment based

these methods use database information regarding structures match homologous structures created protein sequences. these homologous structures assembled give compact structures using scoring , optimization procedures, goal of achieving lowest potential energy score. webservers fragment information listed here: i-tasser, rosetta, rosetta @ home, fragfold, cabs fold, profesy, cref, quark, undertaker, hmm, , anglor.

homology modeling

these methods based upon homology of proteins. these methods known comparative modeling. first step in homology modeling identification of template sequences of known structure homologous query sequence. next query sequence aligned template sequence. following alignment, structurally conserved regions modeled using template structure. followed modeling of side chains , loops distinct template. modeled structure undergoes refirnment , assessment of quality. servers available homology modeling data listed here: swiss model, modeller, reformalign, pymod, tip-structfast, compass, 3d-pssm, samt02, samt99, hhpred, fague, 3d-jigsaw, meta-pp, rosetta, , i-tasser.

protein threading

protein threading can used when reliable homologue query sequence cannot found. method begins obtaining query sequence , library of template structures. next, query sequence threaded on known template structures. these candidate models scored using scoring functions. these scored based upon potential energy models of both query , template sequence. match lowest potential energy model selected. methods , servers retrieving threading data , performing calculations listed here: genthreader, pgenthreader, pdomthreader, orfeus, prospect, bioshell-threading, ffaso3, raptorx, hhpred, loopp server, sparks-x, segmer, threader2, esypred3d, libra, topits, raptor, coth, muster.

for more information on rational design see site-directed mutagenesis.