Enhanced ab initio protein folding simulations in Poisson–Boltzmann molecular dynamics with self-guiding forces

Wen, Edward Z.; Hsieh, Meng-Juei; Kollman, Peter A.; Luo, Ray

doi:10.1016/j.jmgm.2003.12.008

Cited by 43 publications

(33 citation statements)

References 72 publications

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“…Other notable studies include the implicit solvent simulations by Pak and coworkers (19), Scheraga and coworkers (20), and Herges and Wenzel (21). In addition, a variety of advanced techniques have been applied to facilitate the sampling of the native state (22)(23)(24). Nonetheless, the best C ␣ -rmsd sampled during those simulations was typically Ͼ3.0 Å, and the average C ␣ -rmsd of the most sampled conformations was significantly higher.…”

mentioning

confidence: 99%

Folding free-energy landscape of villin headpiece subdomain from molecular dynamics simulations

Lei

Wu²,

Liu³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

232

233

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High-accuracy ab initio folding has remained an elusive objective despite decades of effort. To explore the folding landscape of villin headpiece subdomain HP35, we conducted two sets of replica exchange molecular dynamics for 200 ns each and three sets of conventional microsecond-long molecular dynamics simulations, using AMBER FF03 force field and a generalized-Born solvation model. The protein folded consistently to the native state; the lowest C␣-rmsd from the x-ray structure was 0.46 Å, and the C␣-rmsd of the center of the most populated cluster was 1. Despite decades of effort, high-accuracy ab initio protein folding has remained elusive to the simulation community. Most existing ab initio protein folding simulations have typically been at the 3-4 Å level based on the best C ␣ -rmsd compared with the experimental structures. When heavy-atom rmsd is used, a much larger rmsd (Ͼ5 Å) would be common. Yet, crystals of small proteins that can diffract only at 5-Å resolution are not considered of acceptable quality. Thus, most of the ab initio folding simulations have never reached the native states despite the enormous effort, underscoring the challenge. Because of the lack of accuracy in those simulations, it is impossible to obtain the crucial information on the folding pathways to the native states. This renders great ambiguity to the interpretation of the folding mechanisms. In this work, we demonstrate consistent ab initio protein folding to the native state of HP35.Villin headpiece is an F actin-binding domain that resides in the far C terminal of the super villin (1, 2). The 35-residue C-terminal subdomain HP35 can fold autonomously without the assistance of disulfide bonds or metal ions and has a melting temperature of T m ϭ 342 K, which is surprisingly high for a protein of its size (3-5). HP35 is arguably the smallest native occurring protein with the features of much bigger proteins, where multiple secondary structures (three helices) are bound together by a well packed hydrophobic core (three phenylalanine residues and other hydrophobic residues). As such, unveiling the folding mechanism of HP35 will augment our understanding of protein folding.The unique structural architecture of HP35 was revealed by using both NMR and x-ray crystallography (5, 6). However, the elucidation of the folding mechanism of HP35, remains a long-standing endeavor. In a laser-induced temperature-jump experiment, the quenching of Trp 23 by the engineered His 27 revealed a 4.3-s fast folding (4), which was later confirmed by NMR line-shape analysis (7) and loop-formation dynamics (8).Two kinetic phases, with the time constant of 70 ns and 5 s, were observed experimentally (4), indicating hidden complexities in the folding process. Mutagenesis experiments on the three core phenylalanine residues (9) and the Pro 21 -X 22 -Trp 23 motif (10) demonstrated the contribution from interior and surface residues to the stability. Studies of the HP35 fragments showed that the individual helices are largely unstructured, whereas the frag...

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mentioning

confidence: 99%

Folding free-energy landscape of villin headpiece subdomain from molecular dynamics simulations

Lei

Wu²,

Liu³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

232

233

View full text Add to dashboard Cite

show abstract

“…For example, the self-guided molecular dynamics (SGMD) and self-guided Langevin dynamics (SGLD) were developed based on molecular dynamics or Langevin dynamics. they accelerate conformational search through enhancing low frequency motions of simulation systems (Wu and Wang 1998;Wu and Wang 1999;Wu and Brooks 2003;Wu and Brooks 2011a;Wu and Brooks 2011b) and has been applied in many simulation studies such as protein folding (Wu and Sung 1999;Wu and Wang 2000;Wu and Wang 2001;Wu, Wang et al 2002;Wen, Hsieh et al 2004;Wen and Luo 2004;Wu and Brooks 2004;Lee and Chang 2010;Lee and Olson 2010), ligand binding (Varady, Wu et al 2002), docking (Chandrasekaran, Lee et al 2009), conformational transition (Damjanovic, Miller et al 2008;Damjanovic, Wu et al 2008;Damjanovic, Garcia-Moreno E et al 2009;Pendse, Brooks et al 2010), and surface absorption (Abe and Jitsukawa 2009;Tsuru, Yosuke et al 2010). …”

Section: Other Sampling Methodsmentioning

confidence: 99%

Molecular Simulation with Discrete Fast Fourier Transform

Wu¹,

Brooks²

2012

Fourier Transform - Materials Analysis

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“…This report does not cover the geometry optimization including equilibrium and transition structures, Henkelman et al 2000a;Olsen et al 2004;Schlegel 1982Schlegel , 2003Schlegel , 2011 conformational sampling, (Beusen 1996;Leach 1991;Parish 2002) or global minimum search methodologies, (Floudas & Pardalos 1996;Horst 1995Horst , 2000Torn 1989) which are all important for the studies of computational chemistry and biology. Other related topics, including enhanced sampling methods, (Earl & Deem 2005;Hamelberg et al 2004;Lei & Duan 2007;Okur et al 2006;Sugita 1999;Swendsen & Wang 1986;Thomas et al 2005;Wen et al 2004) simulation of nonequilibrium states, (Bair et al 2002;Cummings & Evans 1992;Hoover 1983;Hoover & Hoover 2005;Kjelstrup & Hafskjold 1996;Li et al 2008;Mundy et al 2000) and minimization methods, (Bonnans 2003;Dennis & Schnabel 1996;Fletcher 2000;Gill 1982;Haslinger & Mäkinen 2003;Nocedal 2006;Scales 1985) are not covered in this chapter either. The curious readers are welcome to read cited references for more information.…”

Section: Introductionmentioning

confidence: 99%

Reaction Path Optimization and Sampling Methods and Their Applications for Rare Events

Tao¹,

Larkin²,

Brooks³

2012

Some Applications of Quantum Mechanics

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Enhanced ab initio protein folding simulations in Poisson–Boltzmann molecular dynamics with self-guiding forces

Cited by 43 publications

References 72 publications

Folding free-energy landscape of villin headpiece subdomain from molecular dynamics simulations

Folding free-energy landscape of villin headpiece subdomain from molecular dynamics simulations

Molecular Simulation with Discrete Fast Fourier Transform

Reaction Path Optimization and Sampling Methods and Their Applications for Rare Events

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