Molecular dynamics of biological macromolecules: A brief history and perspective

Karplus, Martin

doi:10.1002/bip.10266

Cited by 97 publications

(59 citation statements)

References 96 publications

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“…[34,35]). However, to examine biologically-relevant dynamics and interactions, such as folding, protein-protein docking, rearrangement upon ligand binding, and protein assembly, time scales of microseconds and longer are needed.…”

Section: Introductionmentioning

confidence: 99%

Computer Simulations of Alzheimers Amyloid β-Protein Folding and Assembly

Urbanc¹,

Cruz²,

Teplow³

et al. 2006

CAR

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Pathological folding and aggregation of the amyloid -protein (A ) are widely perceived as central to understanding Alzheimer's disease (AD) at the molecular level. Experimental approaches to study A self-assembly are limited, because most relevant aggregates are quasi-stable and inhomogeneous. In contrast, simulations can provide significant insights into the problem, including specific sites in the molecule that would be attractive for drug targeting and details of the assembly pathways leading to the production of toxic assemblies. Here we review computer simulation approaches to understanding the structural biology of A . We discuss the ways in which these simulations help guide experimental work, and in turn, how experimental results guide the development of theoretical and simulation approaches that may be of general utility in understanding pathologic protein folding and assembly.

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Section: Introductionmentioning

confidence: 99%

Computer Simulations of Alzheimers Amyloid β-Protein Folding and Assembly

Urbanc¹,

Cruz²,

Teplow³

et al. 2006

CAR

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“…Kuznetsov and Ulstrup (10) and Schwartz and coworkers (11), for example, have proposed formulations alternative to transition-state theoretical ones, whereas Gao and Truhlar (12) have emphasized that modern versions of transition-state theory, which are very far from ''ultrasimple,'' are extremely robust and versatile. Karplus (13,14) has reviewed the prospects for incorporating into the description other current, innovative forms of theory, particularly dynamical simulations, to provide a more complete and satisfying picture of the details of enzyme catalysis.…”

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confidence: 99%

How an enzyme surmounts the activation energy barrier

Schowen

2003

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

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“…analysis of variance ͉ molecular dynamics M olecular dynamics (MD) simulations are widely used in the study of protein structure and functions (1,2). The results of a given simulation depend on a number of factors, such as the quality of the molecular force field, the treatment of solvent, the timescale of the simulation, and the sampling efficiency of the simulation protocol.…”

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confidence: 99%

Comparative study of generalized Born models: Protein dynamics

Fan

Mark

Zhu

2005

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

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In this work, we compare the results of molecular dynamics simulations involving the application of three generalized Born (GB) models to 10 different proteins. The three GB models, the Still, HCT, and modified analytical generalized Born models, were implemented in the computationally efficient GROMACS package. The performance of each model was assessed from the backbone rms deviation from the native structure, the number of native hydrogen bonds retained in the simulation, and the experimental and calculated radius of gyration. Analysis of variance (ANOVA) was used to analyze the results of the simulations. The rms deviation measure was found to be unable to distinguish the quality of the results obtained with the three different GB models, whereas the number of native hydrogen bonds and radius of gyration yielded a statistically meaningful discrimination among models. Our results suggest that, of the three, modified analytical generalized Born yields the best agreement between calculated and experimentally derived structures. More generally, our study highlights the need both to evaluate the effects of different variables on the results of simulations and to verify that the results of molecular dynamics simulations are statistically meaningful.analysis of variance ͉ molecular dynamics M olecular dynamics (MD) simulations are widely used in the study of protein structure and functions (1, 2). The results of a given simulation depend on a number of factors, such as the quality of the molecular force field, the treatment of solvent, the timescale of the simulation, and the sampling efficiency of the simulation protocol. There has been an enormous investment in the underlying technology in each of these areas, and the range of application of MD simulations has expanded greatly since the method was first introduced (3). However, by their very nature, MD simulations are not easy to compare to experiment. Simulations of protein systems involve a considerable amount of computer time, and the results in general cannot be directly compared with the experimental observables without additional processing. When such comparisons are made, the results are often very encouraging, but, given the multiplicity of parameters and computational methodologies that are used, it is hard to know whether the success of a particular protocol, e.g., using one of the available force fields, indicates that all other force fields will yield results of comparable quality. Fortunately, the growth in available computer power combined with the development of highly optimized computer code has made careful comparison of methods more feasible and, in addition, should make it increasingly possible to test whether a particular result is robust in terms of its sensitivity to the parameters of the calculation. Moreover, it would be highly desirable to know whether a particular methodology or combination of parameters is best suited to a particular application and to understand the reasons for performance differences, to the extent that they exist. Th...

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Molecular dynamics of biological macromolecules: A brief history and perspective

Cited by 97 publications

References 96 publications

Computer Simulations of Alzheimers Amyloid β-Protein Folding and Assembly

Computer Simulations of Alzheimers Amyloid β-Protein Folding and Assembly

How an enzyme surmounts the activation energy barrier

Comparative study of generalized Born models: Protein dynamics

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Molecular dynamics of biological macromolecules: A brief history and perspective

Cited by 97 publications

References 96 publications

Computer Simulations of Alzheimers Amyloid &#946;-Protein Folding and Assembly

Computer Simulations of Alzheimers Amyloid &#946;-Protein Folding and Assembly

How an enzyme surmounts the activation energy barrier

Comparative study of generalized Born models: Protein dynamics

Contact Info

Product

Resources

About

Computer Simulations of Alzheimers Amyloid β-Protein Folding and Assembly

Computer Simulations of Alzheimers Amyloid β-Protein Folding and Assembly