Template based protein structure modeling by global optimization in CASP11

Abstract

For the template-based modeling (TBM) of CASP11 targets, we have developed three new protein modeling protocols (nns for server prediction and LEE and LEER for human prediction) by improving upon our previous CASP protocols (CASP7 through CASP10). We applied the powerful global optimization method of conformational space annealing to three stages of optimization, including multiple sequence-structure alignment, three-dimensional (3D) chain building, and side-chain remodeling. For more successful fold recognition, a new alignment method called CRFalign was developed. It can incorporate sensitive positional and environmental dependence in alignment scores as well as strong nonlinear correlations among various features. Modifications and adjustments were made to the form of the energy function and weight parameters pertaining to the chain building procedure. For the side-chain remodeling step, residue-type dependence was introduced to the cutoff value that determines the entry of a rotamer to the side-chain modeling library. The improved performance of the nns server method is attributed to successful fold recognition achieved by combining several methods including CRFalign and to the current modeling formulation that can incorporate native-like structural aspects present in multiple templates. The LEE protocol is identical to the nns one except that CASP11-released server models are used as templates. The success of LEE in utilizing CASP11 server models indicates that proper template screening and template clustering assisted by appropriate cluster ranking promises a new direction to enhance protein 3D modeling.

Modeling CAPRI targets 110‐120 by template‐based and free docking using contact potential and combined scoring function

“…For the FSA docking, we selected 10 models from different servers with the lowest AACE18 values. However, model 8 (model 1 from GOAL server) produced FSA docking models with F ( S ) < 0.5 only, and thus these results were not included in the final submission. All but two submitted trimers were of acceptable quality (Supporting Information Table S5).…”

Ergodicity and model quality in template‐restrained canonical and temperature/Hamiltonian replica exchange coarse‐grained molecular dynamics simulations of proteins

“…To determine whether the use of HREMD, which exhibits better ergodicity compared to MREMD, can improve the quality of the resulting models, we tried the four CASP11 targets: T0767, T0771, T0802, and T0828, which were treated in our latest work . For each of these proteins, 5 models from each of the nns, BAKER‐ROSETTASERVER, Zhang‐Server, and QUARK servers were used. As mentioned in the Introduction, because the server models of these targets were very divergent, we imposed the restraints only on those fragments which were found to overlap well for all server models.…”

“…None of the server models used to derive the restraints captures the entire fold. In our previous study, using the consensus‐fragments from the nns, BAKER‐ROSETTASERVER, Zhang‐Server, and QUARK server models, we produced a model of better quality for T0828 but not for the remaining three proteins.…”

Engineering of Baeyer-Villiger monooxygenase-based Escherichia coli biocatalyst for large scale biotransformation of ricinoleic acid into (Z)-11-(heptanoyloxy)undec-9-enoic acid

“…One possibility would be generation of salt bridge between Glu residues of the tag and the Arg residue sitting around N-terminal of the BVMO (Supplementary Fig. S11, structure prediction was performed as previously reported44). Since the BVMOs were reported to undergo a great deal of conformational change during catalysis45, the resulting salt bridge might contribute to stabilization of the transition states of the enzyme-NADP(H)-substrate complex in addition to correct folding at high temperatures.…”