Biomedical subjects

Min-yi Shen

Publications and source records attributed to Min-yi Shen.

3 recordsLinked to original sources

PubMed2006

A composite score for predicting errors in protein structure models.

Reliable prediction of model accuracy is an important unsolved problem in protein structure modeling. To address this problem, we studied 24 individual assessment scores, including physics-based energy functions, statistical potentials, and machine learning-based scoring functions. Individual scores were also used to construct approximately 85,000 composite scoring functions using support vector machine (SVM) regression. The scores were tested for their abilities to identify the most native-like models from a set of 6000 comparative models of 20 representative protein structures. Each of the 20 targets was modeled using a template of <30% sequence identity, corresponding to challenging comparative modeling cases. The best SVM score outperformed all individual scores by decreasing the average RMSD difference between the model identified as the best of the set and the model with the lowest RMSD (DeltaRMSD) from 0.63 A to 0.45 A, while having a higher Pearson correlation coefficient to RMSD (r=0.87) than any other tested score. The most accurate score is based on a combination of the DOPE non-hydrogen atom statistical potential; surface, contact, and combined statistical potentials from MODPIPE; and two PSIPRED/DSSP scores. It was implemented in the SVMod program, which can now be applied to select the final model in various modeling problems, including fold assignment, target-template alignment, and loop modeling.

Models, Molecular↗

PubMed2003

Large-scale context in protein folding: villin headpiece.

The villin headpiece folds autonomously in vitro forming three alpha-helical regions. Local propensities, however, strongly disfavor the formation of the C-terminal helix because most native residue pairs in that helix are hydrophobic/polar mismatches. Even the N-terminal helix is unfavored according to the AGADIR criterion. Our coarse-grained ab initio simulations reveal three-body correlations in which hydrophobic residues position to protect amide-carbonyl hydrogen bonds from attack by water, thus inducing the growth of the C-terminal helix and guiding the folding process. Similar correlations are also found in all-atom simulations with an implicit solvent model that accurately reproduces the results of simulations with explicit solvent molecules. The correlations establish a large-scale, many-body context that may be probed experimentally by introducing mutations of certain nonobvious residues that reside outside the native hydrophobic core but that are predicted to affect the folding rates and dynamics dramatically.

Alanine↗

PubMed2002

All-atom fast protein folding simulations: the villin headpiece.

We provide a fast folding simulation using an all-atom solute, implicit solvent method that eliminates the need for treating solvent degrees of freedom. The folding simulations for the 36-residue villin headpiece exhibit close correspondence with the landmark all-atom explicit solvent molecular dynamics simulations by Duan and Kollman (Duan & Kollman, Science 1998;282:740-744; Duan, Wang, & Kollman, Proc Natl Acad Sci USA 1998;95:9897-9902). Our implicit solvent approach uses only an entry-level single CPU PC with comparable throughput ( approximately 4 nsec/day) to the DK supercomputer simulation. The native state is shown to be stable. Our 200-nsec folding trajectory agrees with the DK simulation in displaying a burst phase, a rapid initial shrinkage, a highly native-like binding site structure, and more.

Animals↗