Generalized-ensemble algorithms for molecular simulations of biopolymers

Mitsutake, Ayori; Sugita, Yuji; Okamoto, Yuko

doi:10.1002/1097-0282(2001)60:2<96::aid-bip1007>3.0.co;2-f

Cited by 764 publications

(697 citation statements)

References 138 publications

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“…Adequate sampling of conformational space was insured through the use of the Replica Exchange algorithm. 17,18 REMD was developed as a means to overcome local potential energy barriers. Compiled under AMBER 8, one-dimensional REMD explores a generalized canonical ensemble of N noninteracting replicas that undergo simulation separately but concomitantly at exponentially related temperatures, with exchanges between replicas occurring at a specified time interval.…”

Section: Methodsmentioning

confidence: 99%

Computational Design and Experimental Discovery of an Antiestrogenic Peptide Derived from α-Fetoprotein

et al. 2007

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Breast cancer is the most common cancer among women, and tamoxifen is the preferred drug for estrogen receptor-positive breast cancer treatment. Many of these cancers are intrinsically resistant to tamoxifen or acquire resistance during treatment. Consequently, there is an ongoing need for breast cancer drugs that have different molecular targets. Previous work has shown that 8-mer and cyclic 9-mer peptides inhibit breast cancer in mouse and rat models, interacting with an unsolved receptor, while peptides smaller than eight amino acids did not. We show that the use of replica exchange molecular dynamics predicts the structure and dynamics of active peptides, leading to the discovery of smaller peptides with full biological activity. Simulations identified smaller peptide analogues with the same conserved reverse turn demonstrated in the larger peptides. These analogues were synthesized and shown to inhibit estrogen-dependent cell growth in a mouse uterine growth assay, a test showing reliable correlation with human breast cancer inhibition.

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Section: Methodsmentioning

confidence: 99%

Computational Design and Experimental Discovery of an Antiestrogenic Peptide Derived from α-Fetoprotein

et al. 2007

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“…[20,21] for some examples, and the introduction of STMD [10] was a major step in bridging the gap between MC and MD. Our demonstration that STMD and metadynamics can be made identical should further facilitate technological transfers between both communities.…”

Section: Resultsmentioning

confidence: 99%

Molecular Dynamics in the Multicanonical Ensemble: Equivalence of Wang–Landau Sampling, Statistical Temperature Molecular Dynamics, and Metadynamics

Junghans

Pérez

Vogel

2014

J. Chem. Theory Comput.

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We show direct formal relationship between the Wang-Landau iteration [PRL 86, 2050[PRL 86, (2001], metadynamics [PNAS 99, 12562 (2002)] and statistical temperature molecular dynamics (STMD) [PRL 97, 050601 (2006)], the major work-horses for sampling from generalized ensembles. We demonstrate that STMD, itself derived from the Wang-Landau method, can be made indistinguishable from metadynamics. We also show that Gaussian kernels significantly improve the performance of STMD, highlighting the practical benefits of this improved formal understanding.

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“…Elsewhere, various search methods have been tested in lattice models 26,27,28,29 . However, we were interested in comparing zipping and assembly with replica-exchange methods, which are generalized ensemble approaches to reducing barriers and increasing sampling efficiencies 30,31 . We find that Z&A is consistently more efficient than REMC (replica exchange Monte Carlo) by several orders of magnitude ( Figure 9).…”

Section: Zanda Outperforms Replica-exchange Monte Carlo (Remc) In Reachmentioning

confidence: 99%

Exploring zipping and assembly as a protein folding principle

Voelz

Dill

2007

Proteins

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It has been proposed that proteins fold by a process called "Zipping & Assembly" (Z&A). Zipping refers to the growth of local substructures within the chain, and assembly refers to the coming together of already-formed pieces. Our interest here is in whether Z&A is a general method that can fold most of sequence space, to global minima, efficiently. Using the HP model, we can address this question by enumerating full conformation and sequence spaces. We find that Z&A reaches the global energy minimum native states, even though it searches only a very small fraction of conformational space, for most sequences in the full sequence space. We find that Z&A, a mechanism-based search, is more efficient in our tests than the Replica Exchange search method. Folding efficiency is increased for chains having: (a) small loop-closure steps, consistent with observations by Plaxco et al. 1 that folding rates correlate with contact order, (b) neither too few nor too many nucleation sites per chain, and (c) assembly steps that do not occur too early in the folding process. We find that the efficiency increases with chain length, although our range of chain lengths is limited. We believe these insights may be useful for developing faster protein conformational search algorithms.

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Generalized-ensemble algorithms for molecular simulations of biopolymers

Cited by 764 publications

References 138 publications

Computational Design and Experimental Discovery of an Antiestrogenic Peptide Derived from α-Fetoprotein

Computational Design and Experimental Discovery of an Antiestrogenic Peptide Derived from α-Fetoprotein

Molecular Dynamics in the Multicanonical Ensemble: Equivalence of Wang–Landau Sampling, Statistical Temperature Molecular Dynamics, and Metadynamics

Exploring zipping and assembly as a protein folding principle

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