High accuracy template based modeling by global optimization

Abstract

For high‐accuracy template‐based‐modeling of CASP7 targets, we have applied a procedure based on the rigorous optimization of score functions at three stages: multiple alignment, chain building, and side‐chain modeling. We applied the conformational space annealing method to a newly developed consistency based score function for multiple alignment. For chain building, we optimized the MODELLER energy function. For side‐chain modeling, we optimized a SCWRL‐like energy function using a rotamer library constructed specifically for a given target sequence. By rigorous optimization, we have achieved significant improvement in backbone as well as side‐chain modeling for TBM and TBM/HA targets. For most TBM/HA targets (17/26), the predicted model was more accurate than the model one can construct from the best template in a posteriori fashion. It appears that the current method can extract relevant information out of multiple templates. Proteins 2007. © 2007 Wiley‐Liss, Inc.

Re‐examination of structure optimization of off‐lattice protein AB models by conformational space annealing

“…Low-energy conformations scattered distantly may cover different portions of protein structures, and thus there are more chances to improve the quality of structures by combining the information from diverse low-energy structures. 2 In the three-dimensional model1, these results strongly suggest that ground-states for S 13 , S 21 , and S 34 are found, However, the situation is less clear for the case of S 55 .…”

“…2 Therefore if one can find lower energy conformations, the chances are that the quality of their structures is better. We note that the degrees of freedom of the system S n in three dimensions increases as 2n which corresponds to the number of backbone angles of a protein with n residues.…”

“…Recently the importance of optimization in all stages of protein structure prediction using bioinformatics is also investigated. 2 Simplified protein models such as AB models 3 are devised to study qualitative properties of protein folding. Off-lattice protein AB models consist of hydrophobic monomers labeled by A and hydrophilic ones by B. Interactions between these monomers are composed of a Lennard-Jones type potential term, a bending energy term, and torsional energy contributions.…”

Methods for Accurate Homology Modeling by Global Optimization

“…In the recent CASP experiments (CASP7 and CASP8) for protein structure prediction, the high-accuracy template based modeling (HA-TBM) category is considered separately along with template based modeling (TBM) and free modeling (FM) categories, and there were many examples where protein models were more accurate than the best available templates in terms of accuracies of backbone structure, side-chain orientation, hydrogen bonding and usefulness for molecular replacement in X-ray crystallography [17,11].…”

“…For 3D model building from a few selected alignments, we optimize the MODELLER energy function as rigorously as possible to generate protein structures satisfying as much spatial restraints derived from its alignment as well as proper stereochemistry of proteins [12]. For side-chain remodeling, again we adopt the global optimization method of CSA to determine the orientations of sidechains both in the surface and inside the core area of protein structures [11]. Here the backbone-dependent rotamer library of SCWRL 3.0 is used.…”