Driven to Near-Experimental Accuracy by Refinement via Molecular Dynamics Simulations

By Lim Heo, Collin F Arbour, Michael Feig. 2019

31 citations recorded by the source corpus.

Protein model refinement has been an essential part of successful protein structure prediction. Molecular dynamics simulation‐based refinement methods have shown consistent improvement of protein models. There had been progress in the extent of refinement for a few years since the idea of ensemble averaging of sampled conformations emerged. There was little progress in CASP12 because conformational sampling was not sufficiently diverse due to harmonic restraints. During CASP13, a new refinement method was tested that achieved significant improvements over CASP12. The new method intended to address previous bottlenecks in the refinement problem by introducing new features. Flat‐bottom harmonic restraints replaced harmonic restraints, sampling was performed iteratively, and a new scoring function and selection criteria were used. The new protocol expanded conformational sampling at reduced computational costs. In addition to overall improvements, some models were refined significantly to near‐experimental accuracy.

Subfields: Materials Chemistry, Molecular Biology, Spectroscopy, AI for Physical Sciences

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Materials Chemistry

1. Sergey Ovchinnikov
2. David Baker
3. Ivan V. Anishchenko
4. Hahnbeom Park
5. Yang Zhang
6. Zhenling Peng
7. Jianyi Yang
8. Dima Kozakov

In Molecular Biology

1. Sergey Ovchinnikov
2. David Baker
3. Yang Zhang
4. Ivan V. Anishchenko
5. Hahnbeom Park
6. Zhenling Peng
7. Robin Pearce
8. Jianyi Yang

In Spectroscopy

1. Sergey Ovchinnikov
2. Hahnbeom Park
3. Dima Kozakov
4. Sandor Vajda
5. Bing Xia
6. David Baker
7. Zhenling Peng
8. Ivan V. Anishchenko

In AI for Physical Sciences

1. Sergey Ovchinnikov
2. Hahnbeom Park
3. David Baker
4. Jianyi Yang

Citations in the corpus

• Improved protein structure prediction using predicted interresidue orientations (2019, methodology): “Progress was also evident in protein structure refinement at CASP13 using energy guided refinement (9-11).”
• Performance and its limits in rigid body protein-protein docking (2020, methodology): “Creating such models would require even more fundamental refinement, most likely by Monte Carlo minimization or by molecular dynamics simulation, adopting methods that currently achieved success in protein structure refinement (Heo et al., 2019; Terashi and Kihara, 2018).”