From Protein Structure to Function with Bioinformatics.pdf

1 Ab Initio Protein Structure Prediction 13Fig. 1.4 Flowchart of I-TASSER protein structure modellingwrong topology (>9 Å) but the final model is 3.6 Å away from the X-ray structure.Recently, Helles carried out a comparative study on 18 ab initio prediction algorithmsand concluded that I-TASSER is about the best method in term of the modellingaccuracy and CPU cost per target (Helles 2008).1.3 Conformational Search MethodsSuccessful ab initio modelling of protein structures depends on the availability ofa powerful conformation search method which can efficiently find the globalminimum energy structure for a given energy function with complicated energylandscape. Historically, Monte Carlo and molecular dynamics are two popularsimulation methods to explore the conformational space of macromolecules suchas proteins. For complicated systems like proteins, canonical MD/MC methodsusually require a huge amount of computational resources for a complete explorationof the conformational space. The record for direct application of MD toobtain the protein native structure is not so impressive. One explanation for thefailure could be that the simulation time required to fold a small protein takes aslong as milliseconds, 10 12 times longer than the usual incremental time step offemtoseconds (10 −15 s). The technical difficulty of MC simulations mainly comesfrom that the energy landscape of protein conformational space is typically quite